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["Basic information",null,null,null,null,null,null,null,null,null,null,null,null,"Domain 1. Randomization process",null,null,null,null,null,null,null,null,null,"Domain 2. Deviations from intended interventions",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"Domain 3. Mising outcome data",null,null,null,null,null,null,null,null,null,null,null,null,"Domain 4. Measurement of the outcome",null,null,null,null,null,null,null,null,null,null,null,null,null,null,"Domain 5. Selection of the reported result",null,null,null,null,null,null,null,null,null,null,"Domain 6. Overall Bias"]
["Time","Unique ID","Assessor","Study ID","Reference","Experimental","Comparator","Outcome","Results","Aim","Effect of adhering to intervention?","Weight","Sources","1.1","1.2","Note for 1.1&1.2","1.3","Note for 1.3","1.0 Algorithm result","1.0 Assessor's Judgement","1.0 General note","1.0 Optional Question","1.0 Note for optional question","2.1","2.2","Note for 2.1&2.2","2.3","Note for 2.3","2.4","Note for 2.4","2.5","Note for 2.5","2.6","Note for 2.6","2.7","Note for 2.7","2.0 Algorithm result","2.0 Assessor's Judgement","2.0 General Notes","2.0 Optional Question","2.0 Note for optional question","3.1","Note for 3.1","3.2","Note for 3.2","3.3","Note for 3.3&3.4","3.4","Note for 3.4 (not use)","3.0 Algorithm result","3.0 Assessor's judgement","3.0 Gerenal notes","3.0 Optional Question","3.0 Note for optional question","4.1","Note for 4.1","4.2","Note for 4.2","4.3","Note for 4.3","4.4","Note for 4.4&4.5","4.5","Note for 4.5 (not use)","4.0 Algorithm result","4.0 Assessor's Judgement","4.0 General note","4.0 Optional Question","4.0 Note for optional question","5.1","Note for 5.1","5.2","Note for 5.2","5.3","Note for 5.3","5.0 Algorithm result","5.0 Assessor's Judgement","5.0 General note","5.0 Optional Question","5.0 Note for optional question","Algorithm's overall Judgement","Assessor's overall Judgement","6.0 General Note","6.0 Optional Question","6.0 Note for optional question"]
["2020/12/07 19.15","1_A","LA","Lin 2004","Chinese Journal of Clinical Rehabilitation","Exercise ","No Exercise","All-cause Mortality","RR =4.46 (95% CI 0.22, 90.78)","assignment to intervention (the 'intention-to-treat' effect)","NA",9.9," Journal article(s)","NI","NI","The only information provided about randomization is a statement stating that the patients were randomly divided into experimental or control groups.\r\n\r\nThere is no reference to concealment of allocation sequence. ","N","There seemed to be no imbalance between the two study groups according to baseline characteristics.","Some concerns","Some concerns",null,null,null,"Y","Y","Given the nature of an exercise-based CR intervention, participants are aware of their intervention and it might therefore not be possible to blind them, their carers, or the people delivering this intervention.","NI","The authors did not provide any information to help us ascertain whether people may or may not have deviated from the intended intervention.","NA",null,"NA",null,"NI","The authors did not state if any analysis was carried out to estimate the effect of assignment to the intervention.","PN","There is no reason to believe that participants were excluded from the analysis or assessed in the wrong intervention group.","Some concerns","Some concerns",null,null,null,"PN","The authors reported that only participants who did not drop out and were not lost to follow-up were included in analysis.","PN"," The authors state that they used available case analysis but this does not account for missing data.","PY","Eventhough the outcome is mortality and it is centrally registered, because the trial only included participants who were not lost to follow up, this might have affected the number of recorded deaths by this trial. The authors do not provide enough information to allow us further assess whether or not the missingness depended on its true value","PY",null,"High","High","The authors reported that only participants who did not drop out and were not lost to follow-up were included in analysis.\n The authors state that they used available case analysis but this does not account for missing data.\nEventhough the outcome is mortality and it is centrally registered, because the trial only included participants who were not lost to follow up, this might have affected the number of recorded deaths by this trial. The authors do not provide enough information to allow us further assess whether or not the missingness depended on its true value\n",null,null,"N","Mortality is reported from a central database.","N","Because of the nature of the outcome and due to it being reported centrally, measurement or ascertainment could not have differed between the two groups.","NI","The authors do not provisde any information with regards to blinding of the outcome assessors/assessment.","N","Knowledge of the assigned intervention is unlikely to influence all-cause mortality as this is an observer-reported outcome that does not involve judgement.","NA",null,"Low","Low","Mortality is reported from a central database.\r\nBecause of the nature of the outcome and due to it being reported centrally, measurement or ascertainment could not have differed between the two groups.\r\nThe authors do not provisde any information with regards to blinding of the outcome assessors/assessment.\r\nKnowledge of the assigned intervention is unlikely to influence all-cause mortality as this is an observer-reported outcome that does not involve judgement.\r\n",null,null,"PY","Although there is no published protocol for this study and the authors make no mention as to if there was a pre-specified analysis plan, all-cause mortality is centrally recorded and as such there can not be selection of this outcome.","N","All-cause mortality is centrally recorded and as such there can not be selection of this outcome.","PN","All-cause mortality is centrally recorded and as such there can not be selection of this outcome.","Low","Low","Although there is no published protocol for this study and the authors make no mention as to if there was a pre-specified analysis plan, all-cause mortality is centrally recorded and as such there can not be selection of this outcome.\r\nAll-cause mortality is centrally recorded and as such there can not be selection of this outcome.\r\nAll-cause mortality is centrally recorded and as such there can not be selection of this outcome.",null,null,"High","High","\r\n\r\nThe authors reported that only participants who did not drop out and were not lost to follow-up were included in analysis.\r\n The authors state that they used available case analysis but this does not account for missing data.\r\nEventhough the outcome is mortality and it is centrally registered, because the trial only included participants who were not lost to follow up, this might have affected the number of recorded deaths by this trial. The authors do not provide enough information to allow us further assess whether or not the missingness depended on its true value\r\n\r\nMortality is reported from a central database.\r\nBecause of the nature of the outcome and due to it being reported centrally, measurement or ascertainment could not have differed between the two groups.\r\nThe authors do not provisde any information with regards to blinding of the outcome assessors/assessment.\r\nKnowledge of the assigned intervention is unlikely to influence all-cause mortality as this is an observer-reported outcome that does not involve judgement.\r\n\r\nAlthough there is no published protocol for this study and the authors make no mention as to if there was a pre-specified analysis plan, all-cause mortality is centrally recorded and as such there can not be selection of this outcome.\r\nAll-cause mortality is centrally recorded and as such there can not be selection of this outcome.\r\nAll-cause mortality is centrally recorded and as such there can not be selection of this outcome."]
["2021/02/09 14.49","2_A","LA","Pressler 2018","European Journal of Preventive Cardiology","Exercise","No Exercise","All-cause Mortality","RR = 0.43 (95% CI 0.10, 1.85) (results from fig 1 in article)","assignment to intervention (the 'intention-to-treat' effect)","NA",90.1," Journal article(s)","Y","PY","The authors state that “patients were randomly allocated 1:1 according to a computer-generated allocation program code”.\r\n\r\nAlthough there was no mention of allocation sequence concealment, the fact that they used a computer-generated program code would prevent the enrolling investigator or the participant from having any knowledge of the forthcoming allocation.","N","No differences for TG and UC with respect to age, proportion of females, The Society of Thoracic Surgeons mortality risk score, NYHA class, prexisting conditions, and medication were observed (see Table I). ","Low","Low","The authors state that “patients were randomly allocated 1:1 according to a computer-generated allocation program code”.\r\n\r\nAlthough there was no mention of allocation sequence concealment, the fact that they used a computer-generated program code would prevent the enrolling investigator or the participant from having any knowledge of the forthcoming allocation.\r\nNo differences for TG and UC with respect to age, proportion of females, The Society of Thoracic Surgeons mortality risk score, NYHA class, prexisting conditions, and medication were observed (see Table I). ",null,null,"Y","Y","Given the nature of an exercise-based CR intervention, participants are aware of their intervention and it might therefore not be possible to blind them, their carers, or the people delivering this intervention.","PN","Although the authors do not specifically state if there were any deviations from the intended intervention, the flow of participants through the study (Fig 1 of 2016 paper and fig 1 of 2018 paper) shows that no participant changed groups during the study and all changes to the intervention were either consistent with the intervention (i.e. drop out due to unrelated causes) or consistent with what could occur outside of the trial context (i.e. drop out due to unwillingness to continue participation).","NA",null,"NA",null,"Y","Data were tested for their distribution and the primary end point and key secondary outcomes were normally distributed; thus it was decided to present data as mean (SD). Baseline differences between groups were analyzed using the Student t test for independent samples for continuous variables and the Fisher exact test for categorical variables. Between-group differences in changes of the primary and secondary end points were analyzed using the Student t test for independent samples. For relevant effect sizes (mean differences between study groups), 95% CIs are presented. Because of the low number of dropouts that were all unrelated to the intervention and the primary intention of the study to evaluate efficacy and safety of exercise, a per-protocol analysis was performed. To account for observed differences in baseline parameters between the study groups, linear regression models using the change in the measure of interest as dependent variable and the study group as well as the baseline value of the measure of interest as independent variable were fit to the data. ","NA",null,"Low","Low","Given the nature of an exercise-based CR intervention, participants are aware of their intervention and it might therefore not be possible to blind them, their carers, or the people delivering this intervention.\r\nAlthough the authors do not specifically state if there were any deviations from the intended intervention, the flow of participants through the study (Fig 1 of 2016 paper and fig 1 of 2018 paper) shows that no participant changed groups during the study and all changes to the intervention were either consistent with the intervention (i.e. drop out due to unrelated causes) or consistent with what could occur outside of the trial context (i.e. drop out due to unwillingness to continue participation).\r\n\r\n\r\nData were tested for their distribution and the primary end point and key secondary outcomes were normally distributed; thus it was decided to present data as mean (SD). Baseline differences between groups were analyzed using the Student t test for independent samples for continuous variables and the Fisher exact test for categorical variables. Between-group differences in changes of the primary and secondary end points were analyzed using the Student t test for independent samples. For relevant effect sizes (mean differences between study groups), 95% CIs are presented. Because of the low number of dropouts that were all unrelated to the intervention and the primary intention of the study to evaluate efficacy and safety of exercise, a per-protocol analysis was performed. To account for observed differences in baseline parameters between the study groups, linear regression models using the change in the measure of interest as dependent variable and the study group as well as the baseline value of the measure of interest as independent variable were fit to the data. \r\n",null,null,"Y","Outcome data was present for all participants.","NA",null,"NA",null,"NA",null,"Low","Low",null,null,null,"N","Mortality is reported from a central database.","N","Because of the nature of the outcome and due to it being reported centrally, measurement or ascertainment could not have differed between the two groups.","N","The authors state that 'All endpoints were performed and supervised by experienced staﬀ blinded to original group assignments'.","NA",null,"NA",null,"Low","Low","Mortality is reported from a central database.\r\nBecause of the nature of the outcome and due to it being reported centrally, measurement or ascertainment could not have differed between the two groups.\r\nThe authours state that 'All endpoints were performed and supervised by experienced staﬀ blinded to original group assignments'.\r\n\r\n",null,null,"Y","The trial was registered on clinicaltrials.gov before start of the study (NCT01935297) with researchers’ pre-specified intentions available in sufficient detail. All-cause mortality is however centrally recorded and as such there can not be selection of this outcome.","N","The authors provided results for all timepoints at which this outcome was assessed with all extra analysis intended as exploratory analysis to provide additional information on the group-specific impact of the intervention.","N","The authors reported all results ","Low","Low","The trial was registered on clinicaltrials.gov before start of the study (NCT01935297) with researchers’ pre-specified intentions available in sufficient detail. All-cause mortality is however centrally recorded and as such there can not be selection of this outcome.\r\nThe authors provided results for all timepoints at which this outcome was assessed with all extra analysis intended as exploratory analysis to provide additional information on the group-specific impact of the intervention.\r\nThe authors reported all results ",null,null,"Low","Low","The authors state that “patients were randomly allocated 1:1 according to a computer-generated allocation program code”.\r\n\r\nAlthough there was no mention of allocation sequence concealment, the fact that they used a computer-generated program code would prevent the enrolling investigator or the participant from having any knowledge of the forthcoming allocation.\r\nNo differences for TG and UC with respect to age, proportion of females, The Society of Thoracic Surgeons mortality risk score, NYHA class, prexisting conditions, and medication were observed (see Table I). \r\nGiven the nature of an exercise-based CR intervention, participants are aware of their intervention and it might therefore not be possible to blind them, their carers, or the people delivering this intervention.\r\nAlthough the authors do not specifically state if there were any deviations from the intended intervention, the flow of participants through the study (Fig 1 of 2016 paper and fig 1 of 2018 paper) shows that no participant changed groups during the study and all changes to the intervention were either consistent with the intervention (i.e. drop out due to unrelated causes) or consistent with what could occur outside of the trial context (i.e. drop out due to unwillingness to continue participation).\r\n\r\n\r\nData were tested for their distribution and the primary end point and key secondary outcomes were normally distributed; thus it was decided to present data as mean (SD). Baseline differences between groups were analyzed using the Student t test for independent samples for continuous variables and the Fisher exact test for categorical variables. Between-group differences in changes of the primary and secondary end points were analyzed using the Student t test for independent samples. For relevant effect sizes (mean differences between study groups), 95% CIs are presented. Because of the low number of dropouts that were all unrelated to the intervention and the primary intention of the study to evaluate efficacy and safety of exercise, a per-protocol analysis was performed. To account for observed differences in baseline parameters between the study groups, linear regression models using the change in the measure of interest as dependent variable and the study group as well as the baseline value of the measure of interest as independent variable were fit to the data. \r\n\r\n\r\nMortality is reported from a central database.\r\nBecause of the nature of the outcome and due to it being reported centrally, measurement or ascertainment could not have differed between the two groups.\r\nThe authours state that 'All endpoints were performed and supervised by experienced staﬀ blinded to original group assignments'.\r\n\r\n\r\nThe trial was registered on clinicaltrials.gov before start of the study (NCT01935297) with researchers’ pre-specified intentions available in sufficient detail. All-cause mortality is however centrally recorded and as such there can not be selection of this outcome.\r\nThe authors provided results for all timepoints at which this outcome was assessed with all extra analysis intended as exploratory analysis to provide additional information on the group-specific impact of the intervention.\r\nThe authors reported all results "]
["2020/12/07 15.02","3_A","LA","Sibilitz 2016","Heart 2016; 102: 1995-2003","Exercise","No Exercise","All-cause Hospitalisation","RR = 2.72 (95% CI 0.11, 65.56)","assignment to intervention (the 'intention-to-treat' effect)","NA",100," Journal article(s); Trial protocol","Y","Y","The authors state that “Participants were allocated 1:1 to intervention or control using computer-generated allocation sequence with varying block sizes of 8, 6 and 4, concealed to the investigators by central telephone correspondence with the Copenhagen Trial Unit.”","N","“There was no evidence of baseline imbalances.” Table 1 shows good balance in patient characteristics between groups","Low","Low","The authors state that “Participants were allocated 1:1 to intervention or control using computer-generated allocation sequence with varying block sizes of 8, 6 and 4, concealed to the investigators by central telephone correspondence with the Copenhagen Trial Unit.”\r\n“There was no evidence of baseline imbalances.” Table 1 shows good balance in patient characteristics between groups",null,null,"Y","Y","Given the nature of an exercise-based CR intervention, participants are aware of their intervention and it might therefore not be possible to blind them, their carers, or the people delivering this intervention.","PN","Although te authors do not expressesly mention if there were any deviations from the intended intervention, their CONSORT flow diagram of patients (fig 1 in article) shows that all participants were analysed in their initial intervention group.","NA",null,"NA",null,"Y","The analysis was based on intention to treat using a mixed model with repeated measures (MMRM) and adjusted for the stratification variable of LVEF, ensuring that missing data will not create bias as long as the values are missing at random.25 The MMRM was used for continuous outcomes (both primary and secondary outcomes). This model assumes normally (Gaussian) distributed residuals. However, the residuals were not normally distributed for the primary outcome, and therefore transformed. We used log-transformation, and when log-transformation did not result in normally distributed residuals, we used Box–Cox transformation. In the MMRM we assumed correlation within the individual patient, but no correlation between patients. The fixed effects for the primary outcome were randomisation group, time, interaction between random and time and LVEF.","NA",null,"Low","Low","Given the nature of an exercise-based CR intervention, participants are aware of their intervention and it might therefore not be possible to blind them, their carers, or the people delivering this intervention.\r\nAlthough te authors do not expressesly mention if there were any deviations from the intended intervention, their CONSORT flow diagram of patients (fig 1 in article) shows that all participants were analysed in their initial intervention group.\r\n\r\n\r\nThe analysis was based on intention to treat using a mixed model with repeated measures (MMRM) and adjusted for the stratification variable of LVEF, ensuring that missing data will not create bias as long as the values are missing at random.25 The MMRM was used for continuous outcomes (both primary and secondary outcomes). This model assumes normally (Gaussian) distributed residuals. However, the residuals were not normally distributed for the primary outcome, and therefore transformed. We used log-transformation, and when log-transformation did not result in normally distributed residuals, we used Box–Cox transformation. In the MMRM we assumed correlation within the individual patient, but no correlation between patients. The fixed effects for the primary outcome were randomisation group, time, interaction between random and time and LVEF.\r\n",null,null,"N","Considering the fact that the appropriate study population for an analysis of the intention to treat effect is all randomized participants, in this Trial, less than 95% of the participants in either the exercise group or the control group provided data for this outcome. The authors do state that the drop outs were due to complications after surgery and withdrawal of consent with 9 people dropping out of the study before completing 1 month of exercise training or usual care.","N","There is no evidence to prove that the results was not biased by missing outcome data as the only sensitivity analysis carried out was for VO2.  ","PY","There is no considerable difference in the proportions of missing outcome data between the two groups.\r\nThe authors do state that the drop outs were due to complications after surgery and withdrawal of consent, but no mention was made to suggest that the intervention played a part in this withdrawal.\r\nReported reasons for missing outcome data are similar between both groups.\r\nThe circumstances of the trial do not make it likely that missingness in the outcome depends on its true value as more participants dropped out of the control group than from the exercise group.","N",null,"Some concerns","Some concerns","Considering the fact that the appropriate study population for an analysis of the intention to treat effect is all randomized participants, in this Trial, less than 95% of the participants in either the exercise group or the control group provided data for this outcome. The authors do state that the drop outs were due to complications after surgery and withdrawal of consent with 9 people dropping out of the study before completing 1 month of exercise training or usual care.\r\nThere is no evidence to prove that the results was not biased by missing outcome data as the only sensitivity analysis carried out was for VO2.  \r\nThere is no considerable difference in the proportions of missing outcome data between the two groups.\r\nThe authors do state that the drop outs were due to complications after surgery and withdrawal of consent, but no mention was made to suggest that the intervention played a part in this withdrawal.\r\nReported reasons for missing outcome data are similar between both groups.\r\nThe circumstances of the trial do not make it likely that missingness in the outcome depends on its true value as more participants dropped out of the control group than from the exercise group.\r\n",null,null,"N","Hospitalisation like mortality is centrally reported.","N","Because of its central reporting, measurement or ascertainment could not have differed between the two groups.","N","“The trial applied central, stratified randomisation securing against selection bias, and blinded outcome assessment and blinded statistical analyses, reducing detection and interpretation bias”","NA",null,"NA",null,"Low","Low","Hospitalisation like mortality is centrally reported.\r\nBecause of its central reporting, measurement or ascertainment could not have differed between the two groups.\r\n“The trial applied central, stratified randomisation securing against selection bias, and blinded outcome assessment and blinded statistical analyses, reducing detection and interpretation bias”\r\n\r\n",null,null,"Y","Trial registered on clinicaltrials.gov before start of the study  (NCT01558765) with researchers’ pre-specified intentions available in sufficient detail. The central recording of all-cause hospitalisations however makes it an outcome which can not be selected against.","N","The authors provided results for all timepoints at which this outcome was assessed (6months) within the scope of this article.","N","There is no evidence of multiple eligible analyses for this outcome.","Low","Low","Trial registered on clinicaltrials.gov before start of the study  (NCT01558765) with researchers’ pre-specified intentions available in sufficient detail. The central recording of all-cause hospitalisations however makes it an outcome which can not be selected against.\r\nThe authors provided results for all timepoints at which this outcome was assessed (6months) within the scope of this article.\r\nThere is no evidence of multiple eligible analyses for this outcome.",null,null,"Some concerns","Some concerns","The authors state that “Participants were allocated 1:1 to intervention or control using computer-generated allocation sequence with varying block sizes of 8, 6 and 4, concealed to the investigators by central telephone correspondence with the Copenhagen Trial Unit.”\r\n“There was no evidence of baseline imbalances.” Table 1 shows good balance in patient characteristics between groups\r\nGiven the nature of an exercise-based CR intervention, participants are aware of their intervention and it might therefore not be possible to blind them, their carers, or the people delivering this intervention.\r\nAlthough te authors do not expressesly mention if there were any deviations from the intended intervention, their CONSORT flow diagram of patients (fig 1 in article) shows that all participants were analysed in their initial intervention group.\r\n\r\n\r\nThe analysis was based on intention to treat using a mixed model with repeated measures (MMRM) and adjusted for the stratification variable of LVEF, ensuring that missing data will not create bias as long as the values are missing at random.25 The MMRM was used for continuous outcomes (both primary and secondary outcomes). This model assumes normally (Gaussian) distributed residuals. However, the residuals were not normally distributed for the primary outcome, and therefore transformed. We used log-transformation, and when log-transformation did not result in normally distributed residuals, we used Box–Cox transformation. In the MMRM we assumed correlation within the individual patient, but no correlation between patients. The fixed effects for the primary outcome were randomisation group, time, interaction between random and time and LVEF.\r\n\r\nLess than 95% of the participants in either the exercise group or the control group provided data for this outcome. The authors do state that the drop outs were due to complications after surgery and withdrawal of consent with 9 people dropping out of the study before completing 1 month of exercise training or usual care.\r\nThere is no evidence to prove that the results was not biased by missing outcome data as the only sensitivity analysis carried out was for VO2.  \r\nThere is no considerable difference in the proportions of missing outcome data between the two groups.\r\nThe authors do state that the drop outs were due to complications after surgery and withdrawal of consent, but no mention was made to suggest that the intervention played a part in this withdrawal.\r\nReported reasons for missing outcome data are similar between both groups.\r\nThe circumstances of the trial do not make it likely that missingness in the outcome depends on its true value as more participants dropped out of the control group than from the exercise group.\r\n\r\nHospitalisation like mortality is centrally reported.\r\nBecause of its central reporting, measurement or ascertainment could not have differed between the two groups.\r\n“The trial applied central, stratified randomisation securing against selection bias, and blinded outcome assessment and blinded statistical analyses, reducing detection and interpretation bias”\r\n\r\n\r\nTrial registered on clinicaltrials.gov before start of the study  (NCT01558765) with researchers’ pre-specified intentions available in sufficient detail. The central recording of all-cause hospitalisations however makes it an outcome which can not be selected against.\r\nThe authors provided results for all timepoints at which this outcome was assessed (6months) within the scope of this article.\r\nThere is no evidence of multiple eligible analyses for this outcome."]
["2020/12/07 19.27","2_B","LA","Pressler 2016","American Heart Journal vol 182; pp. 44-53","Exercise","No Exercise","HRQoL (MC at end of intervention)","MD = 3 (95% CI -3.16, 9.16)","assignment to intervention (the 'intention-to-treat' effect)","NA",21.8," Journal article(s)","Y","PY","The authors state that “patients were randomly allocated 1:1 according to a computer-generated allocation program code”.\r\nAlthough there was no mention of allocation sequence concealment, the fact that they used a computer-generated program code would prevent the enrolling investigator or the participant from having any knowledge of the forthcoming allocation.","N","No differences for TG and UC with respect to age, proportion of females, The Society of Thoracic Surgeons mortality risk score, NYHA class, prexisting conditions, and medication were observed (see Table I).","Low","Low","The authors state that “patients were randomly allocated 1:1 according to a computer-generated allocation program code”.\r\nAlthough there was no mention of allocation sequence concealment, the fact that they used a computer-generated program code would prevent the enrolling investigator or the participant from having any knowledge of the forthcoming allocation.\r\nNo differences for TG and UC with respect to age, proportion of females, The Society of Thoracic Surgeons mortality risk score, NYHA class, prexisting conditions, and medication were observed (see Table I).",null,null,"Y","Y","Given the nature of an exercise-based CR intervention, participants are aware of their intervention and it might therefore not be possible to blind them, their carers, or the people delivering this intervention.","PN","Although the authors do not specifically state if there were any deviations from the intended intervention, the flow of participants through the study (Fig 1 of 2016 paper and fig 1 of 2018 paper) shows that no participant changed groups during the study and all changes to the intervention were either consistent with the intervention (i.e. drop out due to unrelated causes) or consistent with what could occur outside of the trial context (i.e. drop out due to unwillingness to continue participation).","NA",null,"NA",null,"Y","Data were tested for their distribution and the primary end point and key secondary outcomes were normally distributed; thus it was decided to present data as mean (SD). Baseline differences between groups were analyzed using the Student t test for independent samples for continuous variables and the Fisher exact test for categorical variables. Between-group differences in changes of the primary and secondary end points were analyzed using the Student t test for independent samples. For relevant effect sizes (mean differences between study groups), 95% CIs are presented. Because of the low number of dropouts that were all unrelated to the intervention and the primary intention of the study to evaluate efficacy and safety of exercise, a per-protocol analysis was performed. To account for observed differences in baseline parameters between the study groups, linear regression models using the change in the measure of interest as dependent variable and the study group as well as the baseline value of the measure of interest as independent variable were fit to the data. ","NA",null,"Low","Low","Given the nature of an exercise-based CR intervention, participants are aware of their intervention and it might therefore not be possible to blind them, their carers, or the people delivering this intervention.\r\nAlthough the authors do not specifically state if there were any deviations from the intended intervention, the flow of participants through the study (Fig 1 of 2016 paper and fig 1 of 2018 paper) shows that no participant changed groups during the study and all changes to the intervention were either consistent with the intervention (i.e. drop out due to unrelated causes) or consistent with what could occur outside of the trial context (i.e. drop out due to unwillingness to continue participation).\r\n\r\n\r\nData were tested for their distribution and the primary end point and key secondary outcomes were normally distributed; thus it was decided to present data as mean (SD). Baseline differences between groups were analyzed using the Student t test for independent samples for continuous variables and the Fisher exact test for categorical variables. Between-group differences in changes of the primary and secondary end points were analyzed using the Student t test for independent samples. For relevant effect sizes (mean differences between study groups), 95% CIs are presented. Because of the low number of dropouts that were all unrelated to the intervention and the primary intention of the study to evaluate efficacy and safety of exercise, a per-protocol analysis was performed. To account for observed differences in baseline parameters between the study groups, linear regression models using the change in the measure of interest as dependent variable and the study group as well as the baseline value of the measure of interest as independent variable were fit to the data. \r\n",null,null,"N","Considering the fact that the appropriate study population for an analysis of the intention to treat effect is all randomized participants, in this Trial,  less than 95% of the participants in either the exercise group or the control group provided data for this outcome, as there were 3 overall drop outs (2/15 in exercise group and 1/15 in control group). ","Y","Because of the low number of dropouts that were all unrelated to the intervention and the primary intention of the study to evaluate efficacy and safety of exercise, a per-protocol analysis was performed.","NA",null,"NA",null,"Low","Low","Considering the fact that the appropriate study population for an analysis of the intention to treat effect is all randomized participants, in this Trial,  less than 95% of the participants in either the exercise group or the control group provided data for this outcome, as there were 3 overall drop outs (2/15 in exercise group and 1/15 in control group). \r\nBecause of the low number of dropouts that were all unrelated to the intervention and the primary intention of the study to evaluate efficacy and safety of exercise, a per-protocol analysis was performed.\r\n\r\n",null,null,"N","HRQoL measured using SF36 and KCCQ both of which are validated questionnaires","N","Measurements were made in the same way for both intervention and control ","Y","The person reporting this outcome is the participant and they are aware of the intervention received. Collation and analysis of the results were most likely carried out by study personnel who were blinded to the intervention recived by the study participant.","Y","The assessment by the participants could have been affected by knowledge of the intervention as it is subjective. Exercise is generally believed to be a beneficial intervention in this patient group and it is possible that participants might have considered their HRQoL would be better if they had the intervention.","PY",null,"High","High","HRQoL measured using SF36 and KCCQ both of which are validated questionnaires\r\nMeasurements were made in the same way for both intervention and control \r\nThe person reporting this outcome is the participant and they are aware of the intervention received. Collation and analysis of the results were most likely carried out by study personnel who were blinded to the intervention recived by the study participant.\r\nThe assessment by the participants could have been affected by knowledge of the intervention as it is subjective. Exercise is generally believed to be a beneficial intervention in this patient group and it is possible that participants might have considered their HRQoL would be better if they had the intervention.\r\n",null,null,"Y","The trial was registered on clinicaltrials.gov before start of the study (NCT01935297) with researchers’ pre-specified intentions available in sufficient detail. There is no reason to believe that the data which produced this result was not analysed in accordance with a pre-specified analysis plan.","N","The authors provided results for all timepoints at which this outcome was assessed with all extra analysis intended as exploratory analysis to provide additional information on the group-specific impact of the intervention.","N","The authors reported all results. There is therefore no reason to believe that this result might have been selected from multiple eligible analyses of the data.","Low","Low","The trial was registered on clinicaltrials.gov before start of the study (NCT01935297) with researchers’ pre-specified intentions available in sufficient detail. There is no reason to believe that the data which produced this result was not analysed in accordance with a pre-specified analysis plan.\r\nThe authors provided results for all timepoints at which this outcome was assessed with all extra analysis intended as exploratory analysis to provide additional information on the group-specific impact of the intervention.\r\nThe authors reported all results. There is therefore no reason to believe that this result might have been selected from multiple eligible analyses of the data.",null,null,"High","High","The authors state that “patients were randomly allocated 1:1 according to a computer-generated allocation program code”.\r\nAlthough there was no mention of allocation sequence concealment, the fact that they used a computer-generated program code would prevent the enrolling investigator or the participant from having any knowledge of the forthcoming allocation.\r\nNo differences for TG and UC with respect to age, proportion of females, The Society of Thoracic Surgeons mortality risk score, NYHA class, prexisting conditions, and medication were observed (see Table I).\r\nGiven the nature of an exercise-based CR intervention, participants are aware of their intervention and it might therefore not be possible to blind them, their carers, or the people delivering this intervention.\r\nAlthough the authors do not specifically state if there were any deviations from the intended intervention, the flow of participants through the study (Fig 1 of 2016 paper and fig 1 of 2018 paper) shows that no participant changed groups during the study and all changes to the intervention were either consistent with the intervention (i.e. drop out due to unrelated causes) or consistent with what could occur outside of the trial context (i.e. drop out due to unwillingness to continue participation).\r\n\r\n\r\nData were tested for their distribution and the primary end point and key secondary outcomes were normally distributed; thus it was decided to present data as mean (SD). Baseline differences between groups were analyzed using the Student t test for independent samples for continuous variables and the Fisher exact test for categorical variables. Between-group differences in changes of the primary and secondary end points were analyzed using the Student t test for independent samples. For relevant effect sizes (mean differences between study groups), 95% CIs are presented. Because of the low number of dropouts that were all unrelated to the intervention and the primary intention of the study to evaluate efficacy and safety of exercise, a per-protocol analysis was performed. To account for observed differences in baseline parameters between the study groups, linear regression models using the change in the measure of interest as dependent variable and the study group as well as the baseline value of the measure of interest as independent variable were fit to the data. \r\n\r\nConsidering the fact that the appropriate study population for an analysis of the intention to treat effect is all randomized participants, in this Trial,  less than 95% of the participants in either the exercise group or the control group provided data for this outcome, as there were 3 overall drop outs. \r\nBecause of the low number of dropouts that were all unrelated to the intervention and the primary intention of the study to evaluate efficacy and safety of exercise, a per-protocol analysis was performed.\r\n\r\n\r\nHRQoL measured using SF36 and KCCQ both of which are validated questionnaires\r\nMeasurements were made in the same way for both intervention and control \r\nThe person reporting this outcome is the participant and they are aware of the intervention received. Collation and analysis of the results were most likely carried out by study personnel who were blinded to the intervention recived by the study participant.\r\nThe assessment by the participants could have been affected by knowledge of the intervention as it is subjective. Exercise is generally believed to be a beneficial intervention in this patient group and it is possible that participants might have considered their HRQoL would be better if they had the intervention.\r\n\r\nThe trial was registered on clinicaltrials.gov before start of the study (NCT01935297) with researchers’ pre-specified intentions available in sufficient detail. There is no reason to believe that the data which produced this result was not analysed in accordance with a pre-specified analysis plan. \r\nThe authors provided results for all timepoints at which this outcome was assessed with all extra analysis intended as exploratory analysis to provide additional information on the group-specific impact of the intervention.\r\nThe authors reported all results. There is therefore no reason to believe that this result might have been selected from multiple eligible analyses of the data."]
["2020/12/07 16.01","3_B","LA","Sibilitz 2016","Heart 2016; 102: 1995-2003","Exercise","No Exercise","HRQoL (MC at end of intervention)","MD = 0.80 (95% CI -2.46, 4.06)","assignment to intervention (the 'intention-to-treat' effect)","NA",78.2," Journal article(s)","Y","Y","The authors state that “Participants were allocated 1:1 to intervention or control using computer-generated allocation sequence with varying block sizes of 8, 6 and 4, concealed to the investigators by central telephone correspondence with the Copenhagen Trial Unit.”","N","“There was no evidence of baseline imbalances.” Table 1 shows good balance in patient characteristics between groups","Low","Low","The authors state that “Participants were allocated 1:1 to intervention or control using computer-generated allocation sequence with varying block sizes of 8, 6 and 4, concealed to the investigators by central telephone correspondence with the Copenhagen Trial Unit.”\r\n“There was no evidence of baseline imbalances.” Table 1 shows good balance in patient characteristics between groups",null,null,"Y","Y","Given the nature of an exercise-based CR intervention, participants are aware of their intervention and it might therefore not be possible to blind them, their carers, or the people delivering this intervention.","PN","Although te authors do not expressesly mention if there were any deviations from the intended intervention, their CONSORT flow diagram of patients (fig 1 in article) shows that all participants were analysed in their initial intervention group.","NA",null,"NA",null,"Y","The analysis was based on intention to treat using a mixed model with repeated measures (MMRM) and adjusted for the stratification variable of LVEF, ensuring that missing data will not create bias as long as the values are missing at random.25 The MMRM was used for continuous outcomes (both primary and secondary outcomes). This model assumes normally (Gaussian) distributed residuals. However, the residuals were not normally distributed for the primary outcome, and therefore transformed. We used log-transformation, and when log-transformation did not result in normally distributed residuals, we used Box–Cox transformation. In the MMRM we assumed correlation within the individual patient, but no correlation between patients. The fixed effects for the primary outcome were randomisation group, time, interaction between random and time and LVEF.","NA",null,"Low","Low","Given the nature of an exercise-based CR intervention, participants are aware of their intervention and it might therefore not be possible to blind them, their carers, or the people delivering this intervention.\r\nAlthough te authors do not expressesly mention if there were any deviations from the intended intervention, their CONSORT flow diagram of patients (fig 1 in article) shows that all participants were analysed in their initial intervention group.\r\n\r\n\r\nThe analysis was based on intention to treat using a mixed model with repeated measures (MMRM) and adjusted for the stratification variable of LVEF, ensuring that missing data will not create bias as long as the values are missing at random.25 The MMRM was used for continuous outcomes (both primary and secondary outcomes). This model assumes normally (Gaussian) distributed residuals. However, the residuals were not normally distributed for the primary outcome, and therefore transformed. We used log-transformation, and when log-transformation did not result in normally distributed residuals, we used Box–Cox transformation. In the MMRM we assumed correlation within the individual patient, but no correlation between patients. The fixed effects for the primary outcome were randomisation group, time, interaction between random and time and LVEF.\r\n",null,null,"N","Considering the fact that the appropriate study population for an analysis of the intention to treat effect is all randomized participants, in this Trial,  less than 95% of the participants in either the exercise group or the control group provided data for this outcome. The authors do state that the drop outs were due to complications after surgery and withdrawal of consent with 9 people dropping out of the study before completing 1 month of exercise training or usual care.","N","There is no evidence to prove that the results was not biased by missing outcome data","PY","There is no considerable difference in the proportions of missing outcome data between the two groups.\r\nThe authors do state that the drop outs were due to complications after surgery and withdrawal of consent, but no mention was made to suggest that the intervention played a part in this withdrawal.\r\nReported reasons for missing outcome data are similar between both groups.\r\nThe circumstances of the trial do not make it likely that missingness in the outcome depends on its true value as more participants dropped out of the control group than from the exercise group.","N",null,"Some concerns","Some concerns","Considering the fact that the appropriate study population for an analysis of the intention to treat effect is all randomized participants, in this Trial,  less than 95% of the participants in either the exercise group or the control group provided data for this outcome. The authors do state that the drop outs were due to complications after surgery and withdrawal of consent with 9 people dropping out of the study before completing 1 month of exercise training or usual care.\r\nThere is no evidence to prove that the results was not biased by missing outcome data\r\nThere is no considerable difference in the proportions of missing outcome data between the two groups.\r\nThe authors do state that the drop outs were due to complications after surgery and withdrawal of consent, but no mention was made to suggest that the intervention played a part in this withdrawal.\r\nReported reasons for missing outcome data are similar between both groups.\r\nThe circumstances of the trial do not make it likely that missingness in the outcome depends on its true value as more participants dropped out of the control group than from the exercise group.\r\n",null,null,"N","HRQoL measured using SF36, a validated questionnaire","N","Measurements were made in the same way for both intervention and control ","Y","The person reporting this outcome is the participant and they are aware of the intervention they received. Collation and analysis of the results were most likely arried out by study personnel who were blinded. \r\n“The trial applied central, stratified randomisation securing against selection bias, and blinded outcome assessment and blinded statistical analyses, reducing detection and interpretation bias”","Y","The assessment by the participants could have been affected by knowledge of the intervention as it is subjective. Exercise is generally believed to be a beneficial intervention in this patient group and it is possible that participants might have considered their HRQoL would be better if they had the intervention.","PY",null,"High","High","HRQoL measured using SF36, a validated questionnaire\r\nMeasurements were made in the same way for both intervention and control \r\nThe person reporting this outcome is the participant and they are aware of the intervention they received. Collation and analysis of the results were most likely arried out by study personnel who were blinded. \r\n“The trial applied central, stratified randomisation securing against selection bias, and blinded outcome assessment and blinded statistical analyses, reducing detection and interpretation bias”\r\nThe assessment by the participants could have been affected by knowledge of the intervention as it is subjective. Exercise is generally believed to be a beneficial intervention in this patient group and it is possible that participants might have considered their HRQoL would be better if they had the intervention.\r\n",null,null,"Y","Trial registered on clinicaltrials.gov before start of the study  (NCT01558765) with researchers’ pre-specified intentions available in sufficient detail. There is therefore no reason to believe that the reults would not have been analysed in accordance with a pre-specified analysis plan.","N","The authors provided results for all timepoints at which this outcome was assessed within the scope of this article.","N","There is no evidence of multiple eligible analyses for this outcome.","Low","Low","Trial registered on clinicaltrials.gov before start of the study  (NCT01558765) with researchers’ pre-specified intentions available in sufficient detail. There is therefore no reason to believe that the reults would not have been analysed in accordance with a pre-specified analysis plan.\r\nThe authors provided results for all timepoints at which this outcome was assessed within the scope of this article.\r\nThere is no evidence of multiple eligible analyses for this outcome.",null,null,"High","High","The authors state that “Participants were allocated 1:1 to intervention or control using computer-generated allocation sequence with varying block sizes of 8, 6 and 4, concealed to the investigators by central telephone correspondence with the Copenhagen Trial Unit.”\r\n“There was no evidence of baseline imbalances.” Table 1 shows good balance in patient characteristics between groups\r\nGiven the nature of an exercise-based CR intervention, participants are aware of their intervention and it might therefore not be possible to blind them, their carers, or the people delivering this intervention.\r\nAlthough te authors do not expressesly mention if there were any deviations from the intended intervention, their CONSORT flow diagram of patients (fig 1 in article) shows that all participants were analysed in their initial intervention group.\r\n\r\n\r\nThe analysis was based on intention to treat using a mixed model with repeated measures (MMRM) and adjusted for the stratification variable of LVEF, ensuring that missing data will not create bias as long as the values are missing at random.25 The MMRM was used for continuous outcomes (both primary and secondary outcomes). This model assumes normally (Gaussian) distributed residuals. However, the residuals were not normally distributed for the primary outcome, and therefore transformed. We used log-transformation, and when log-transformation did not result in normally distributed residuals, we used Box–Cox transformation. In the MMRM we assumed correlation within the individual patient, but no correlation between patients. The fixed effects for the primary outcome were randomisation group, time, interaction between random and time and LVEF.\r\n\r\nConsidering the fact that the appropriate study population for an analysis of the intention to treat effect is all randomized participants, in this Trial,  less than 95% of the participants in either the exercise group or the control group provided data for this outcome. The authors do state that the drop outs were due to complications after surgery and withdrawal of consent with 9 people dropping out of the study before completing 1 month of exercise training or usual care.\r\nThere is no evidence to prove that the results was not biased by missing outcome data\r\nThere is no considerable difference in the proportions of missing outcome data between the two groups.\r\nThe authors do state that the drop outs were due to complications after surgery and withdrawal of consent, but no mention was made to suggest that the intervention played a part in this withdrawal.\r\nReported reasons for missing outcome data are similar between both groups.\r\nThe circumstances of the trial do not make it likely that missingness in the outcome depends on its true value as more participants dropped out of the control group than from the exercise group.\r\n\r\nHRQoL measured using SF36, a validated questionnaire\r\nMeasurements were made in the same way for both intervention and control \r\nThe person reporting this outcome is the participant and they are aware of the intervention they received. Collation and analysis of the results were most likely arried out by study personnel who were blinded. \r\n“The trial applied central, stratified randomisation securing against selection bias, and blinded outcome assessment and blinded statistical analyses, reducing detection and interpretation bias”\r\nThe assessment by the participants could have been affected by knowledge of the intervention as it is subjective. Exercise is generally believed to be a beneficial intervention in this patient group and it is possible that participants might have considered their HRQoL would be better if they had the intervention.\r\n\r\nTrial registered on clinicaltrials.gov before start of the study  (NCT01558765) with researchers’ pre-specified intentions available in sufficient detail. There is therefore no reason to believe that the reults would not have been analysed in accordance with a pre-specified analysis plan.\r\nThe authors provided results for all timepoints at which this outcome was assessed within the scope of this article.\r\nThere is no evidence of multiple eligible analyses for this outcome."]
["2020/12/07 19.28","2_C","LA","Pressler 2016","American Heart Journal vol 182; pp. 44-53","Exercise","No Exercise","HRQoL (PC at end of intervention)","MD = 7.9 (95% CI 0.73, 15.07)","assignment to intervention (the 'intention-to-treat' effect)","NA",42.2," Journal article(s)","Y","PY","The authors state that “patients were randomly allocated 1:1 according to a computer-generated allocation program code”.\r\n\r\nAlthough there was no mention of allocation sequence concealment, the fact that they used a computer-generated program code would prevent the enrolling investigator or the participant from having any knowledge of the forthcoming allocation.","N","No differences for TG and UC with respect to age, proportion of females, The Society of Thoracic Surgeons mortality risk score, NYHA class, prexisting conditions, and medication were observed (see Table I). ","Low","Low","The authors state that “patients were randomly allocated 1:1 according to a computer-generated allocation program code”.\r\n\r\nAlthough there was no mention of allocation sequence concealment, the fact that they used a computer-generated program code would prevent the enrolling investigator or the participant from having any knowledge of the forthcoming allocation.\r\nNo differences for TG and UC with respect to age, proportion of females, The Society of Thoracic Surgeons mortality risk score, NYHA class, prexisting conditions, and medication were observed (see Table I). ",null,null,"Y","Y","Given the nature of an exercise-based CR intervention, participants are aware of their intervention and it might therefore not be possible to blind them, their carers, or the people delivering this intervention.","N","Although the authors do not specifically state if there were any deviations from the intended intervention, the flow of participants through the study (Fig 1 of 2016 paper) shows that no participant changed groups during the study and all changes to the intervention were either consistent with the intervention (i.e. drop out due to unrelated causes) or consistent with what could occur outside of the trial context (i.e. drop out due to unwillingness to continue participation).","NA",null,"NA",null,"Y","Data were tested for their distribution and the primary end point and key secondary outcomes were normally distributed; thus it was decided to present data as mean (SD). Baseline differences between groups were analyzed using the Student t test for independent samples for continuous variables and the Fisher exact test for categorical variables. Between-group differences in changes of the primary and secondary end points were analyzed using the Student t test for independent samples. For relevant effect sizes (mean differences between study groups), 95% CIs are presented. Because of the low number of dropouts that were all unrelated to the intervention and the primary intention of the study to evaluate efficacy and safety of exercise, a per-protocol analysis was performed. To account for observed differences in baseline parameters between the study groups, linear regression models using the change in the measure of interest as dependent variable and the study group as well as the baseline value of the measure of interest as independent variable were fit to the data. ","NA",null,"Low","Low","Given the nature of an exercise-based CR intervention, participants are aware of their intervention and it might therefore not be possible to blind them, their carers, or the people delivering this intervention.\r\nAlthough the authors do not specifically state if there were any deviations from the intended intervention, the flow of participants through the study (Fig 1 of 2016 paper) shows that no participant changed groups during the study and all changes to the intervention were either consistent with the intervention (i.e. drop out due to unrelated causes) or consistent with what could occur outside of the trial context (i.e. drop out due to unwillingness to continue participation).\r\n\r\n\r\nData were tested for their distribution and the primary end point and key secondary outcomes were normally distributed; thus it was decided to present data as mean (SD). Baseline differences between groups were analyzed using the Student t test for independent samples for continuous variables and the Fisher exact test for categorical variables. Between-group differences in changes of the primary and secondary end points were analyzed using the Student t test for independent samples. For relevant effect sizes (mean differences between study groups), 95% CIs are presented. Because of the low number of dropouts that were all unrelated to the intervention and the primary intention of the study to evaluate efficacy and safety of exercise, a per-protocol analysis was performed. To account for observed differences in baseline parameters between the study groups, linear regression models using the change in the measure of interest as dependent variable and the study group as well as the baseline value of the measure of interest as independent variable were fit to the data. \r\n",null,null,"N","Considering the fact that the appropriate study population for an analysis of the intention to treat effect is all randomized participants, in this Trial,  less than 95% of the participants in either the exercise group or the control group provided data for this outcome, as there were 3 overall drop outs (2/15 in exercise group and 1/15 in control group). ","Y","Because of the low number of dropouts that were all unrelated to the intervention and the primary intention of the study to evaluate efficacy and safety of exercise, a per-protocol analysis was performed.","NA",null,"NA",null,"Low","Low","Considering the fact that the appropriate study population for an analysis of the intention to treat effect is all randomized participants, in this Trial,  less than 95% of the participants in either the exercise group or the control group provided data for this outcome, as there were 3 overall drop outs (2/15 in exercise group and 1/15 in control group). \r\nBecause of the low number of dropouts that were all unrelated to the intervention and the primary intention of the study to evaluate efficacy and safety of exercise, a per-protocol analysis was performed.\r\n\r\n",null,null,"N","HRQoL measured using SF36 and KCCQ both of which are validated questionnaires","N","Measurements were made in the same way for both intervention and control ","Y","The person reporting this outcome is the participant and they are aware of the intervention received. Collation and analysis of the results were most likely carried out by study personnel who were blinded to the intervention recived by the study participant.","Y","The assessment by the participants could have been affected by knowledge of the intervention as it is subjective. Exercise is generally believed to be a beneficial intervention in this patient group and it is possible that participants might have considered their HRQoL would be better if they had the intervention.","PY",null,"High","High","HRQoL measured using SF36 and KCCQ both of which are validated questionnaires\r\nMeasurements were made in the same way for both intervention and control \r\nThe person reporting this outcome is the participant and they are aware of the intervention received. Collation and analysis of the results were most likely carried out by study personnel who were blinded to the intervention recived by the study participant.\r\nThe assessment by the participants could have been affected by knowledge of the intervention as it is subjective. Exercise is generally believed to be a beneficial intervention in this patient group and it is possible that participants might have considered their HRQoL would be better if they had the intervention.\r\n",null,null,"Y","The trial was registered on clinicaltrials.gov before start of the study (NCT01935297) with researchers’ pre-specified intentions available in sufficient detail. There is no reason to believe that the data which produced this result was not analysed in accordance with a pre-specified analysis plan.","N","The authors provided results for all timepoints at which this outcome was assessed with all extra analysis intended as exploratory analysis to provide additional information on the group-specific impact of the intervention.","N","The authors reported all results. There is therefore no reason to believe that this result might have been selected from multiple eligible analyses of the data.","Low","Low","The trial was registered on clinicaltrials.gov before start of the study (NCT01935297) with researchers’ pre-specified intentions available in sufficient detail. There is no reason to believe that the data which produced this result was not analysed in accordance with a pre-specified analysis plan.\r\nThe authors provided results for all timepoints at which this outcome was assessed with all extra analysis intended as exploratory analysis to provide additional information on the group-specific impact of the intervention.\r\nThe authors reported all results. There is therefore no reason to believe that this result might have been selected from multiple eligible analyses of the data.",null,null,"High","High","The authors state that “patients were randomly allocated 1:1 according to a computer-generated allocation program code”.\r\n\r\nAlthough there was no mention of allocation sequence concealment, the fact that they used a computer-generated program code would prevent the enrolling investigator or the participant from having any knowledge of the forthcoming allocation.\r\nNo differences for TG and UC with respect to age, proportion of females, The Society of Thoracic Surgeons mortality risk score, NYHA class, prexisting conditions, and medication were observed (see Table I). \r\nGiven the nature of an exercise-based CR intervention, participants are aware of their intervention and it might therefore not be possible to blind them, their carers, or the people delivering this intervention.\r\nAlthough the authors do not specifically state if there were any deviations from the intended intervention, the flow of participants through the study (Fig 1 of 2016 paper) shows that no participant changed groups during the study and all changes to the intervention were either consistent with the intervention (i.e. drop out due to unrelated causes) or consistent with what could occur outside of the trial context (i.e. drop out due to unwillingness to continue participation).\r\n\r\n\r\nData were tested for their distribution and the primary end point and key secondary outcomes were normally distributed; thus it was decided to present data as mean (SD). Baseline differences between groups were analyzed using the Student t test for independent samples for continuous variables and the Fisher exact test for categorical variables. Between-group differences in changes of the primary and secondary end points were analyzed using the Student t test for independent samples. For relevant effect sizes (mean differences between study groups), 95% CIs are presented. Because of the low number of dropouts that were all unrelated to the intervention and the primary intention of the study to evaluate efficacy and safety of exercise, a per-protocol analysis was performed. To account for observed differences in baseline parameters between the study groups, linear regression models using the change in the measure of interest as dependent variable and the study group as well as the baseline value of the measure of interest as independent variable were fit to the data. \r\n\r\nConsidering the fact that the appropriate study population for an analysis of the intention to treat effect is all randomized participants, in this Trial,  less than 95% of the participants in either the exercise group or the control group provided data for this outcome, as there were 3 overall drop outs. \r\nBecause of the low number of dropouts that were all unrelated to the intervention and the primary intention of the study to evaluate efficacy and safety of exercise, a per-protocol analysis was performed.\r\n\r\n\r\nHRQoL measured using SF36 and KCCQ both of which are validated questionnaires\r\nMeasurements were made in the same way for both intervention and control \r\nThe person reporting this outcome is the participant and they are aware of the intervention received. Collation and analysis of the results were most likely carried out by study personnel who were blinded to the intervention recived by the study participant.\r\nThe assessment by the participants could have been affected by knowledge of the intervention as it is subjective. Exercise is generally believed to be a beneficial intervention in this patient group and it is possible that participants might have considered their HRQoL would be better if they had the intervention.\r\n\r\nThe trial was registered on clinicaltrials.gov before start of the study (NCT01935297) with researchers’ pre-specified intentions available in sufficient detail. There is no reason to believe that the data which produced this result was not analysed in accordance with a pre-specified analysis plan.\r\nThe authors provided results for all timepoints at which this outcome was assessed with all extra analysis intended as exploratory analysis to provide additional information on the group-specific impact of the intervention.\r\nThe authors reported all results. There is therefore no reason to believe that this result might have been selected from multiple eligible analyses of the data."]
["2020/11/27 01.17","3_C","LA","Sibilitz 2016","Heart 2016; 102: 1995-2003","Exercise","No Exercise","HRQoL (PC at end of intervention)","MD = -0.60 (95% CI -3.43, 2.23)","assignment to intervention (the 'intention-to-treat' effect)","NA",57.8,null,"Y","Y","The authors state that “Participants were allocated 1:1 to intervention or control using computer-generated allocation sequence with varying block sizes of 8, 6 and 4, concealed to the investigators by central telephone correspondence with the Copenhagen Trial Unit.”","N","“There was no evidence of baseline imbalances.” Table 1 shows good balance in patient characteristics between groups","Low","Low","The authors state that “Participants were allocated 1:1 to intervention or control using computer-generated allocation sequence with varying block sizes of 8, 6 and 4, concealed to the investigators by central telephone correspondence with the Copenhagen Trial Unit.”\r\n“There was no evidence of baseline imbalances.” Table 1 shows good balance in patient characteristics between groups",null,null,"Y","Y","Given the nature of an exercise-based CR intervention, participants are aware of their intervention and it might therefore not be possible to blind them, their carers, or the people delivering this intervention.","N","Although te authors do not expressesly mention if there were any deviations from the intended intervention, their CONSORT flow diagram of patients (fig 1 in article) shows that all participants were analysed in their initial intervention group.","NA",null,"NA",null,"Y","The analysis was based on intention to treat using a mixed model with repeated measures (MMRM) and adjusted for the stratification variable of LVEF, ensuring that missing data will not create bias as long as the values are missing at random.25 The MMRM was used for continuous outcomes (both primary and secondary outcomes). This model assumes normally (Gaussian) distributed residuals. However, the residuals were not normally distributed for the primary outcome, and therefore transformed. We used log-transformation, and when log-transformation did not result in normally distributed residuals, we used Box–Cox transformation. In the MMRM we assumed correlation within the individual patient, but no correlation between patients. The fixed effects for the primary outcome were randomisation group, time, interaction between random and time and LVEF.","NA",null,"Low","Low","Given the nature of an exercise-based CR intervention, participants are aware of their intervention and it might therefore not be possible to blind them, their carers, or the people delivering this intervention.\r\nAlthough te authors do not expressesly mention if there were any deviations from the intended intervention, their CONSORT flow diagram of patients (fig 1 in article) shows that all participants were analysed in their initial intervention group.\r\n\r\n\r\nThe analysis was based on intention to treat using a mixed model with repeated measures (MMRM) and adjusted for the stratification variable of LVEF, ensuring that missing data will not create bias as long as the values are missing at random.25 The MMRM was used for continuous outcomes (both primary and secondary outcomes). This model assumes normally (Gaussian) distributed residuals. However, the residuals were not normally distributed for the primary outcome, and therefore transformed. We used log-transformation, and when log-transformation did not result in normally distributed residuals, we used Box–Cox transformation. In the MMRM we assumed correlation within the individual patient, but no correlation between patients. The fixed effects for the primary outcome were randomisation group, time, interaction between random and time and LVEF.\r\n",null,null,"N","Considering the fact that the appropriate study population for an analysis of the intention to treat effect is all randomized participants, in this Trial,  less than 95% of the participants in either the exercise group or the control group provided data for this outcome. The authors do state that the drop outs were due to complications after surgery and withdrawal of consent with 9 people dropping out of the study before completing 1 month of exercise training or usual care.","N","There is no evidence to prove that the results was not biased by missing outcome data","PY","There is no considerable difference in the proportions of missing outcome data between the two groups.\r\nThe authors do state that the drop outs were due to complications after surgery and withdrawal of consent, but no mention was made to suggest that the intervention played a part in this withdrawal.\r\nReported reasons for missing outcome data are similar between both groups.\r\nThe circumstances of the trial do not make it likely that missingness in the outcome depends on its true value as more participants dropped out of the control group than from the exercise group.","N",null,"Some concerns","Some concerns","Considering the fact that the appropriate study population for an analysis of the intention to treat effect is all randomized participants, in this Trial,  less than 95% of the participants in either the exercise group or the control group provided data for this outcome. The authors do state that the drop outs were due to complications after surgery and withdrawal of consent with 9 people dropping out of the study before completing 1 month of exercise training or usual care.\r\nThere is no evidence to prove that the results was not biased by missing outcome data\r\nThere is no considerable difference in the proportions of missing outcome data between the two groups.\r\nThe authors do state that the drop outs were due to complications after surgery and withdrawal of consent, but no mention was made to suggest that the intervention played a part in this withdrawal.\r\nReported reasons for missing outcome data are similar between both groups.\r\nThe circumstances of the trial do not make it likely that missingness in the outcome depends on its true value as more participants dropped out of the control group than from the exercise group.\r\n",null,null,"N","HRQoL measured using SF36, a validated questionnaire","N","Measurements were made in the same way for both intervention and control ","Y","The person reporting this outcome is the participant and they are aware of the intervention they received. Collation and analysis of the results were most likely arried out by study personnel who were blinded. ","Y","“The trial applied central, stratified randomisation securing against selection bias, and blinded outcome assessment and blinded statistical analyses, reducing detection and interpretation bias”\r\nThe assessment by the participants could have been affected by knowledge of the intervention as it is subjective. Exercise is generally believed to be a beneficial intervention in this patient group and it is possible that participants might have considered their HRQoL would be better if they had the intervention.","PY",null,"High","High","HRQoL measured using SF36, a validated questionnaire\r\nMeasurements were made in the same way for both intervention and control \r\nThe person reporting this outcome is the participant and they are aware of the intervention they received. Collation and analysis of the results were most likely arried out by study personnel who were blinded. \r\n“The trial applied central, stratified randomisation securing against selection bias, and blinded outcome assessment and blinded statistical analyses, reducing detection and interpretation bias”\r\nThe assessment by the participants could have been affected by knowledge of the intervention as it is subjective. Exercise is generally believed to be a beneficial intervention in this patient group and it is possible that participants might have considered their HRQoL would be better if they had the intervention.\r\n",null,null,"Y","Trial registered on clinicaltrials.gov before start of the study  (NCT01558765) with researchers’ pre-specified intentions available in sufficient detail. There is therefore no reason to believe that the reults would not have been analysed in accordance with a pre-specified analysis plan.","N","The authors provided results for all timepoints at which this outcome was assessed within the scope of this article.","N","There is no evidence of multiple eligible analyses for this outcome.","Low","Low","Trial registered on clinicaltrials.gov before start of the study  (NCT01558765) with researchers’ pre-specified intentions available in sufficient detail. There is therefore no reason to believe that the reults would not have been analysed in accordance with a pre-specified analysis plan.\r\nThe authors provided results for all timepoints at which this outcome was assessed within the scope of this article.\r\nThere is no evidence of multiple eligible analyses for this outcome.",null,null,"High","High","The authors state that “Participants were allocated 1:1 to intervention or control using computer-generated allocation sequence with varying block sizes of 8, 6 and 4, concealed to the investigators by central telephone correspondence with the Copenhagen Trial Unit.”\r\n“There was no evidence of baseline imbalances.” Table 1 shows good balance in patient characteristics between groups\r\nGiven the nature of an exercise-based CR intervention, participants are aware of their intervention and it might therefore not be possible to blind them, their carers, or the people delivering this intervention.\r\nAlthough te authors do not expressesly mention if there were any deviations from the intended intervention, their CONSORT flow diagram of patients (fig 1 in article) shows that all participants were analysed in their initial intervention group.\r\n\r\n\r\nThe analysis was based on intention to treat using a mixed model with repeated measures (MMRM) and adjusted for the stratification variable of LVEF, ensuring that missing data will not create bias as long as the values are missing at random.25 The MMRM was used for continuous outcomes (both primary and secondary outcomes). This model assumes normally (Gaussian) distributed residuals. However, the residuals were not normally distributed for the primary outcome, and therefore transformed. We used log-transformation, and when log-transformation did not result in normally distributed residuals, we used Box–Cox transformation. In the MMRM we assumed correlation within the individual patient, but no correlation between patients. The fixed effects for the primary outcome were randomisation group, time, interaction between random and time and LVEF.\r\n\r\nConsidering the fact that the appropriate study population for an analysis of the intention to treat effect is all randomized participants, in this Trial,  less than 95% of the participants in either the exercise group or the control group provided data for this outcome. The authors do state that the drop outs were due to complications after surgery and withdrawal of consent with 9 people dropping out of the study before completing 1 month of exercise training or usual care.\r\nThere is no evidence to prove that the results was not biased by missing outcome data\r\nThere is no considerable difference in the proportions of missing outcome data between the two groups.\r\nThe authors do state that the drop outs were due to complications after surgery and withdrawal of consent, but no mention was made to suggest that the intervention played a part in this withdrawal.\r\nReported reasons for missing outcome data are similar between both groups.\r\nThe circumstances of the trial do not make it likely that missingness in the outcome depends on its true value as more participants dropped out of the control group than from the exercise group.\r\n\r\nHRQoL measured using SF36, a validated questionnaire\r\nMeasurements were made in the same way for both intervention and control \r\nThe person reporting this outcome is the participant and they are aware of the intervention they received. Collation and analysis of the results were most likely arried out by study personnel who were blinded. \r\n“The trial applied central, stratified randomisation securing against selection bias, and blinded outcome assessment and blinded statistical analyses, reducing detection and interpretation bias”\r\nThe assessment by the participants could have been affected by knowledge of the intervention as it is subjective. Exercise is generally believed to be a beneficial intervention in this patient group and it is possible that participants might have considered their HRQoL would be better if they had the intervention.\r\n\r\nTrial registered on clinicaltrials.gov before start of the study  (NCT01558765) with researchers’ pre-specified intentions available in sufficient detail. There is therefore no reason to believe that the reults would not have been analysed in accordance with a pre-specified analysis plan.\r\nThe authors provided results for all timepoints at which this outcome was assessed within the scope of this article.\r\nThere is no evidence of multiple eligible analyses for this outcome."]
["2020/12/07 19.30","2_D","LA","Pressler 2016","American Heart Journal vol 182; pp. 44-53","Exercise","No Exercise","HRQoL (MC at maximum follow up)","MD = -1 (95% CI -11.27, 9.27)","assignment to intervention (the 'intention-to-treat' effect)","NA",10," Journal article(s)","Y","Y","The authors state that “patients were randomly allocated 1:1 according to a computer-generated allocation program code”.\r\nAlthough there was no mention of allocation sequence concealment, the fact that they used a computer-generated program code would prevent the enrolling investigator or the participant from having any knowledge of the forthcoming allocation.","N","No differences for TG and UC with respect to age, proportion of females, The Society of Thoracic Surgeons mortality risk score, NYHA class, prexisting conditions, and medication were observed (see Table I). ","Low","Low","The authors state that “patients were randomly allocated 1:1 according to a computer-generated allocation program code”.\r\nAlthough there was no mention of allocation sequence concealment, the fact that they used a computer-generated program code would prevent the enrolling investigator or the participant from having any knowledge of the forthcoming allocation.\r\nNo differences for TG and UC with respect to age, proportion of females, The Society of Thoracic Surgeons mortality risk score, NYHA class, prexisting conditions, and medication were observed (see Table I). ",null,null,"Y","Y","Given the nature of an exercise-based CR intervention, participants are aware of their intervention and it might therefore not be possible to blind them, their carers, or the people delivering this intervention.","N","Although the authors do not specifically state if there were any deviations from the intended intervention, the flow of participants through the study (Fig 1 of 2016 paper) shows that no participant changed groups during the study and all changes to the intervention were either consistent with the intervention (i.e. drop out due to unrelated causes) or consistent with what could occur outside of the trial context (i.e. drop out due to unwillingness to continue participation).","NA",null,"NA",null,"Y","Data were tested for their distribution and the primary end point and key secondary outcomes were normally distributed; thus it was decided to present data as mean (SD). Baseline differences between groups were analyzed using the Student t test for independent samples for continuous variables and the Fisher exact test for categorical variables. Between-group differences in changes of the primary and secondary end points were analyzed using the Student t test for independent samples. For relevant effect sizes (mean differences between study groups), 95% CIs are presented. Because of the low number of dropouts that were all unrelated to the intervention and the primary intention of the study to evaluate efficacy and safety of exercise, a per-protocol analysis was performed. To account for observed differences in baseline parameters between the study groups, linear regression models using the change in the measure of interest as dependent variable and the study group as well as the baseline value of the measure of interest as independent variable were fit to the data. ","NA",null,"Low","Low","Given the nature of an exercise-based CR intervention, participants are aware of their intervention and it might therefore not be possible to blind them, their carers, or the people delivering this intervention.\r\nAlthough the authors do not specifically state if there were any deviations from the intended intervention, the flow of participants through the study (Fig 1 of 2016 paper) shows that no participant changed groups during the study and all changes to the intervention were either consistent with the intervention (i.e. drop out due to unrelated causes) or consistent with what could occur outside of the trial context (i.e. drop out due to unwillingness to continue participation).\r\n\r\n\r\nData were tested for their distribution and the primary end point and key secondary outcomes were normally distributed; thus it was decided to present data as mean (SD). Baseline differences between groups were analyzed using the Student t test for independent samples for continuous variables and the Fisher exact test for categorical variables. Between-group differences in changes of the primary and secondary end points were analyzed using the Student t test for independent samples. For relevant effect sizes (mean differences between study groups), 95% CIs are presented. Because of the low number of dropouts that were all unrelated to the intervention and the primary intention of the study to evaluate efficacy and safety of exercise, a per-protocol analysis was performed. To account for observed differences in baseline parameters between the study groups, linear regression models using the change in the measure of interest as dependent variable and the study group as well as the baseline value of the measure of interest as independent variable were fit to the data. \r\n",null,null,"N","Considering the fact that the appropriate study population for an analysis of the intention to treat effect is all randomized participants, in this Trial,  less than 95% of the participants in either the exercise group or the control group provided data for this outcome. ","N","There is no evidence to suggest that the result was not biased by missing outcome data","Y","Although reported reasons for missing outcome data are similar between both groups.There is no considerable difference in the proportions of missing outcome data between the two groups overall with 5 patient data missing from the exercise group and 8 patient data missing from the control group. Most of the missing data was due to death or other health conditions not necessarily related to the intervention. The circumstances of the trial do not make it likely that missingness in the outcome depends on its true value as more participants dropped out of the control group than from the exercise group.","PN",null,"Some concerns","Some concerns","Considering the fact that the appropriate study population for an analysis of the intention to treat effect is all randomized participants, in this Trial,  less than 95% of the participants in either the exercise group or the control group provided data for this outcome, as there were 3 overall drop outs. \r\nThere is no evidence to suggest that the result was not biased by missing outcome data\r\nAlthough reported reasons for missing outcome data are similar between both groups.There is no considerable difference in the proportions of missing outcome data between the two groups overall with 5 patient data missing from the exercise group and 8 patient data missing from the control group. Most of the missing data was due to death or other health conditions not necessarily related to the intervention. The circumstances of the trial do not make it likely that missingness in the outcome depends on its true value as more participants dropped out of the control group than from the exercise group.\r\n",null,null,"N","HRQoL measured using SF36 and KCCQ both of which are validated questionnaires","N","Measurements were made in the same way for both intervention and control ","Y","The person reporting this outcome is the participant and they are aware of the intervention received. Collation and analysis of the results were most likely carried out by study personnel who were blinded to the intervention recived by the study participant.","Y","The assessment by the participants could have been affected by knowledge of the intervention as it is subjective. Exercise is generally believed to be a beneficial intervention in this patient group and it is possible that participants might have considered their HRQoL would be better if they had the intervention.","PY",null,"High","High","HRQoL measured using SF36 and KCCQ both of which are validated questionnaires\r\nMeasurements were made in the same way for both intervention and control \r\nThe person reporting this outcome is the participant and they are aware of the intervention received. Collation and analysis of the results were most likely carried out by study personnel who were blinded to the intervention recived by the study participant.\r\nThe assessment by the participants could have been affected by knowledge of the intervention as it is subjective. Exercise is generally believed to be a beneficial intervention in this patient group and it is possible that participants might have considered their HRQoL would be better if they had the intervention.\r\n",null,null,"Y","The trial was registered on clinicaltrials.gov before start of the study (NCT01935297) with researchers’ pre-specified intentions available in sufficient detail. There is no reason to believe that the data which produced this result was not analysed in accordance with a pre-specified analysis plan.","N","The authors provided results for all timepoints at which this outcome was assessed with all extra analysis intended as exploratory analysis to provide additional information on the group-specific impact of the intervention.","N","The authors reported all results. There is therefore no reason to believe that this result might have been selected from multiple eligible analyses of the data.","Low","Low","The trial was registered on clinicaltrials.gov before start of the study (NCT01935297) with researchers’ pre-specified intentions available in sufficient detail. There is no reason to believe that the data which produced this result was not analysed in accordance with a pre-specified analysis plan.\r\nThe authors provided results for all timepoints at which this outcome was assessed with all extra analysis intended as exploratory analysis to provide additional information on the group-specific impact of the intervention.\r\nThe authors reported all results. There is therefore no reason to believe that this result might have been selected from multiple eligible analyses of the data.",null,null,"High","High","The authors state that “patients were randomly allocated 1:1 according to a computer-generated allocation program code”.\r\nAlthough there was no mention of allocation sequence concealment, the fact that they used a computer-generated program code would prevent the enrolling investigator or the participant from having any knowledge of the forthcoming allocation.\r\nNo differences for TG and UC with respect to age, proportion of females, The Society of Thoracic Surgeons mortality risk score, NYHA class, prexisting conditions, and medication were observed (see Table I). \r\nGiven the nature of an exercise-based CR intervention, participants are aware of their intervention and it might therefore not be possible to blind them, their carers, or the people delivering this intervention.\r\nAlthough the authors do not specifically state if there were any deviations from the intended intervention, the flow of participants through the study (Fig 1 of 2016 paper) shows that no participant changed groups during the study and all changes to the intervention were either consistent with the intervention (i.e. drop out due to unrelated causes) or consistent with what could occur outside of the trial context (i.e. drop out due to unwillingness to continue participation).\r\n\r\n\r\nData were tested for their distribution and the primary end point and key secondary outcomes were normally distributed; thus it was decided to present data as mean (SD). Baseline differences between groups were analyzed using the Student t test for independent samples for continuous variables and the Fisher exact test for categorical variables. Between-group differences in changes of the primary and secondary end points were analyzed using the Student t test for independent samples. For relevant effect sizes (mean differences between study groups), 95% CIs are presented. Because of the low number of dropouts that were all unrelated to the intervention and the primary intention of the study to evaluate efficacy and safety of exercise, a per-protocol analysis was performed. To account for observed differences in baseline parameters between the study groups, linear regression models using the change in the measure of interest as dependent variable and the study group as well as the baseline value of the measure of interest as independent variable were fit to the data. \r\n\r\nConsidering the fact that the appropriate study population for an analysis of the intention to treat effect is all randomized participants, in this Trial,  less than 95% of the participants in either the exercise group or the control group provided data for this outcome, as there were 3 overall drop outs. \r\nThere is no evidence to suggest that the result was not biased by missing outcome data\r\nAlthough reported reasons for missing outcome data are similar between both groups.There is no considerable difference in the proportions of missing outcome data between the two groups overall with 5 patient data missing from the exercise group and 8 patient data missing from the control group. Most of the missing data was due to death or other health conditions not necessarily related to the intervention. The circumstances of the trial do not make it likely that missingness in the outcome depends on its true value as more participants dropped out of the control group than from the exercise group.\r\n\r\nHRQoL measured using SF36 and KCCQ both of which are validated questionnaires\r\nMeasurements were made in the same way for both intervention and control \r\nThe person reporting this outcome is the participant and they are aware of the intervention received. Collation and analysis of the results were most likely carried out by study personnel who were blinded to the intervention recived by the study participant.\r\nThe assessment by the participants could have been affected by knowledge of the intervention as it is subjective. Exercise is generally believed to be a beneficial intervention in this patient group and it is possible that participants might have considered their HRQoL would be better if they had the intervention.\r\n\r\nThe trial was registered on clinicaltrials.gov before start of the study (NCT01935297) with researchers’ pre-specified intentions available in sufficient detail. There is no reason to believe that the data which produced this result was not analysed in accordance with a pre-specified analysis plan.\r\nThe authors provided results for all timepoints at which this outcome was assessed with all extra analysis intended as exploratory analysis to provide additional information on the group-specific impact of the intervention.\r\nThe authors reported all results. There is therefore no reason to believe that this result might have been selected from multiple eligible analyses of the data."]
["2020/11/27 02.36","3_D","LA","Sibilitz 2016","Heart 2016; 102: 1995-2003","Exercise","No Exercise","HRQoL (MC at maximum follow up)","MD = -1.5 (95% CI -4.93, 1.93)","assignment to intervention (the 'intention-to-treat' effect)","NA",90," Journal article(s)","Y","Y","The authors state that “Participants were allocated 1:1 to intervention or control using computer-generated allocation sequence with varying block sizes of 8, 6 and 4, concealed to the investigators by central telephone correspondence with the Copenhagen Trial Unit.”","N","“There was no evidence of baseline imbalances.” Table 1 shows good balance in patient characteristics between groups","Low","Low","The authors state that “Participants were allocated 1:1 to intervention or control using computer-generated allocation sequence with varying block sizes of 8, 6 and 4, concealed to the investigators by central telephone correspondence with the Copenhagen Trial Unit.”\r\n“There was no evidence of baseline imbalances.” Table 1 shows good balance in patient characteristics between groups",null,null,"Y","Y","Given the nature of an exercise-based CR intervention, participants are aware of their intervention and it might therefore not be possible to blind them, their carers, or the people delivering this intervention.","N","Although te authors do not expressesly mention if there were any deviations from the intended intervention, their CONSORT flow diagram of patients (fig 1 in article) shows that all participants were analysed in their initial intervention group.","NA",null,"NA",null,"Y","The analysis was based on intention to treat using a mixed model with repeated measures (MMRM) and adjusted for the stratification variable of LVEF, ensuring that missing data will not create bias as long as the values are missing at random.25 The MMRM was used for continuous outcomes (both primary and secondary outcomes). This model assumes normally (Gaussian) distributed residuals. However, the residuals were not normally distributed for the primary outcome, and therefore transformed. We used log-transformation, and when log-transformation did not result in normally distributed residuals, we used Box–Cox transformation. In the MMRM we assumed correlation within the individual patient, but no correlation between patients. The fixed effects for the primary outcome were randomisation group, time, interaction between random and time and LVEF.","NA",null,"Low","Low","Given the nature of an exercise-based CR intervention, participants are aware of their intervention and it might therefore not be possible to blind them, their carers, or the people delivering this intervention.\r\nAlthough te authors do not expressesly mention if there were any deviations from the intended intervention, their CONSORT flow diagram of patients (fig 1 in article) shows that all participants were analysed in their initial intervention group.\r\n\r\n\r\nThe analysis was based on intention to treat using a mixed model with repeated measures (MMRM) and adjusted for the stratification variable of LVEF, ensuring that missing data will not create bias as long as the values are missing at random.25 The MMRM was used for continuous outcomes (both primary and secondary outcomes). This model assumes normally (Gaussian) distributed residuals. However, the residuals were not normally distributed for the primary outcome, and therefore transformed. We used log-transformation, and when log-transformation did not result in normally distributed residuals, we used Box–Cox transformation. In the MMRM we assumed correlation within the individual patient, but no correlation between patients. The fixed effects for the primary outcome were randomisation group, time, interaction between random and time and LVEF.\r\n",null,null,"N","Considering the fact that the appropriate study population for an analysis of the intention to treat effect is all randomized participants, in this Trial,  less than 95% of the participants in either the exercise group or the control group provided data for this outcome. The authors do state that the drop outs were due to complications after surgery and withdrawal of consent with 9 people dropping out of the study before completing 1 month of exercise training or usual care.","N","There is no evidence to prove that the results was not biased by missing outcome data","Y","There is no considerable difference in the proportions of missing outcome data between the two groups.\r\nThe authors do state that the drop outs were due to complications after surgery and withdrawal of consent, but no mention was made to suggest that the intervention played a part in this withdrawal.\r\nReported reasons for missing outcome data are similar between both groups.\r\nThe circumstances of the trial do not make it likely that missingness in the outcome depends on its true value as more participants dropped out of the control group than from the exercise group.","PN",null,"Some concerns","Some concerns","Considering the fact that the appropriate study population for an analysis of the intention to treat effect is all randomized participants, in this Trial,  less than 95% of the participants in either the exercise group or the control group provided data for this outcome. The authors do state that the drop outs were due to complications after surgery and withdrawal of consent with 9 people dropping out of the study before completing 1 month of exercise training or usual care.\r\nThere is no evidence to prove that the results was not biased by missing outcome data\r\nThere is no considerable difference in the proportions of missing outcome data between the two groups.\r\nThe authors do state that the drop outs were due to complications after surgery and withdrawal of consent, but no mention was made to suggest that the intervention played a part in this withdrawal.\r\nReported reasons for missing outcome data are similar between both groups.\r\nThe circumstances of the trial do not make it likely that missingness in the outcome depends on its true value as more participants dropped out of the control group than from the exercise group.\r\n",null,null,"N","HRQoL measured using SF36, a validated questionnaire","N","Measurements were made in the same way for both intervention and control ","Y","The person reporting this outcome is the participant and they are aware of the intervention they received. Collation and analysis of the results were most likely arried out by study personnel who were blinded. ","Y","“The trial applied central, stratified randomisation securing against selection bias, and blinded outcome assessment and blinded statistical analyses, reducing detection and interpretation bias”\r\nThe assessment by the participants could have been affected by knowledge of the intervention as it is subjective. Exercise is generally believed to be a beneficial intervention in this patient group and it is possible that participants might have considered their HRQoL would be better if they had the intervention.","PY",null,"High","High","HRQoL measured using SF36, a validated questionnaire\r\nMeasurements were made in the same way for both intervention and control \r\nThe person reporting this outcome is the participant and they are aware of the intervention they received. Collation and analysis of the results were most likely arried out by study personnel who were blinded. \r\n“The trial applied central, stratified randomisation securing against selection bias, and blinded outcome assessment and blinded statistical analyses, reducing detection and interpretation bias”\r\nThe assessment by the participants could have been affected by knowledge of the intervention as it is subjective. Exercise is generally believed to be a beneficial intervention in this patient group and it is possible that participants might have considered their HRQoL would be better if they had the intervention.\r\n",null,null,"Y","Trial registered on clinicaltrials.gov before start of the study  (NCT01558765) with researchers’ pre-specified intentions available in sufficient detail. There is therefore no reason to believe that the reults would not have been analysed in accordance with a pre-specified analysis plan.","N","The authors provided results for all timepoints at which this outcome was assessed within the scope of this article.","N","There is no evidence of multiple eligible analyses for this outcome.","Low","Low","Trial registered on clinicaltrials.gov before start of the study  (NCT01558765) with researchers’ pre-specified intentions available in sufficient detail. There is therefore no reason to believe that the reults would not have been analysed in accordance with a pre-specified analysis plan.\r\nThe authors provided results for all timepoints at which this outcome was assessed within the scope of this article.\r\nThere is no evidence of multiple eligible analyses for this outcome.",null,null,"High","High","The authors state that “Participants were allocated 1:1 to intervention or control using computer-generated allocation sequence with varying block sizes of 8, 6 and 4, concealed to the investigators by central telephone correspondence with the Copenhagen Trial Unit.”\r\n“There was no evidence of baseline imbalances.” Table 1 shows good balance in patient characteristics between groups\r\nGiven the nature of an exercise-based CR intervention, participants are aware of their intervention and it might therefore not be possible to blind them, their carers, or the people delivering this intervention.\r\nAlthough te authors do not expressesly mention if there were any deviations from the intended intervention, their CONSORT flow diagram of patients (fig 1 in article) shows that all participants were analysed in their initial intervention group.\r\n\r\n\r\nThe analysis was based on intention to treat using a mixed model with repeated measures (MMRM) and adjusted for the stratification variable of LVEF, ensuring that missing data will not create bias as long as the values are missing at random.25 The MMRM was used for continuous outcomes (both primary and secondary outcomes). This model assumes normally (Gaussian) distributed residuals. However, the residuals were not normally distributed for the primary outcome, and therefore transformed. We used log-transformation, and when log-transformation did not result in normally distributed residuals, we used Box–Cox transformation. In the MMRM we assumed correlation within the individual patient, but no correlation between patients. The fixed effects for the primary outcome were randomisation group, time, interaction between random and time and LVEF.\r\n\r\nConsidering the fact that the appropriate study population for an analysis of the intention to treat effect is all randomized participants, in this Trial,  less than 95% of the participants in either the exercise group or the control group provided data for this outcome. The authors do state that the drop outs were due to complications after surgery and withdrawal of consent with 9 people dropping out of the study before completing 1 month of exercise training or usual care.\r\nThere is no evidence to prove that the results was not biased by missing outcome data\r\nThere is no considerable difference in the proportions of missing outcome data between the two groups.\r\nThe authors do state that the drop outs were due to complications after surgery and withdrawal of consent, but no mention was made to suggest that the intervention played a part in this withdrawal.\r\nReported reasons for missing outcome data are similar between both groups.\r\nThe circumstances of the trial do not make it likely that missingness in the outcome depends on its true value as more participants dropped out of the control group than from the exercise group.\r\n\r\nHRQoL measured using SF36, a validated questionnaire\r\nMeasurements were made in the same way for both intervention and control \r\nThe person reporting this outcome is the participant and they are aware of the intervention they received. Collation and analysis of the results were most likely arried out by study personnel who were blinded. \r\n“The trial applied central, stratified randomisation securing against selection bias, and blinded outcome assessment and blinded statistical analyses, reducing detection and interpretation bias”\r\nThe assessment by the participants could have been affected by knowledge of the intervention as it is subjective. Exercise is generally believed to be a beneficial intervention in this patient group and it is possible that participants might have considered their HRQoL would be better if they had the intervention.\r\n\r\nTrial registered on clinicaltrials.gov before start of the study  (NCT01558765) with researchers’ pre-specified intentions available in sufficient detail. There is therefore no reason to believe that the reults would not have been analysed in accordance with a pre-specified analysis plan.\r\nThe authors provided results for all timepoints at which this outcome was assessed within the scope of this article.\r\nThere is no evidence of multiple eligible analyses for this outcome."]
["2021/02/09 15.07","3_E","LA","Sibilitz 2016","Heart 2016; 102: 1995-2003","Exercise","No Exercise","HRQoL (PC at maximum follow up)","MD = -1 (95% CI -3.79, 1.79)","assignment to intervention (the 'intention-to-treat' effect)","NA",93.8," Journal article(s)","Y","Y","The authors state that “Participants were allocated 1:1 to intervention or control using computer-generated allocation sequence with varying block sizes of 8, 6 and 4, concealed to the investigators by central telephone correspondence with the Copenhagen Trial Unit.”\r\n","N","“There was no evidence of baseline imbalances.” Table 1 shows good balance in patient characteristics between groups","Low","Low","The authors state that “Participants were allocated 1:1 to intervention or control using computer-generated allocation sequence with varying block sizes of 8, 6 and 4, concealed to the investigators by central telephone correspondence with the Copenhagen Trial Unit.”\r\n\r\n“There was no evidence of baseline imbalances.” Table 1 shows good balance in patient characteristics between groups",null,null,"Y","Y","Given the nature of an exercise-based CR intervention, participants are aware of their intervention and it might therefore not be possible to blind them, their carers, or the people delivering this intervention.\r\n","N","Although te authors do not expressesly mention if there were any deviations from the intended intervention, their CONSORT flow diagram of patients (fig 1 in article) shows that all participants were analysed in their initial intervention group.","NA",null,"NA",null,"Y","The analysis was based on intention to treat using a mixed model with repeated measures (MMRM) and adjusted for the stratification variable of LVEF, ensuring that missing data will not create bias as long as the values are missing at random.25 The MMRM was used for continuous outcomes (both primary and secondary outcomes). This model assumes normally (Gaussian) distributed residuals. However, the residuals were not normally distributed for the primary outcome, and therefore transformed. We used log-transformation, and when log-transformation did not result in normally distributed residuals, we used Box–Cox transformation. In the MMRM we assumed correlation within the individual patient, but no correlation between patients. The fixed effects for the primary outcome were randomisation group, time, interaction between random and time and LVEF.","NA",null,"Low","Low","Given the nature of an exercise-based CR intervention, participants are aware of their intervention and it might therefore not be possible to blind them, their carers, or the people delivering this intervention.\r\n\r\nAlthough te authors do not expressesly mention if there were any deviations from the intended intervention, their CONSORT flow diagram of patients (fig 1 in article) shows that all participants were analysed in their initial intervention group.\r\n\r\n\r\nThe analysis was based on intention to treat using a mixed model with repeated measures (MMRM) and adjusted for the stratification variable of LVEF, ensuring that missing data will not create bias as long as the values are missing at random.25 The MMRM was used for continuous outcomes (both primary and secondary outcomes). This model assumes normally (Gaussian) distributed residuals. However, the residuals were not normally distributed for the primary outcome, and therefore transformed. We used log-transformation, and when log-transformation did not result in normally distributed residuals, we used Box–Cox transformation. In the MMRM we assumed correlation within the individual patient, but no correlation between patients. The fixed effects for the primary outcome were randomisation group, time, interaction between random and time and LVEF.\r\n",null,null,"N","Considering the fact that the appropriate study population for an analysis of the intention to treat effect is all randomized participants, in this Trial,  less than 95% of the participants in either the exercise group or the control group provided data for this outcome. The authors do state that the drop outs were due to complications after surgery and withdrawal of consent with 9 people dropping out of the study before completing 1 month of exercise training or usual care.","N","There is no evidence to prove that the results was not biased by missing outcome data","Y","There is no considerable difference in the proportions of missing outcome data between the two groups.\r\nThe authors do state that the drop outs were due to complications after surgery and withdrawal of consent, but no mention was made to suggest that the intervention played a part in this withdrawal.\r\nReported reasons for missing outcome data are similar between both groups.\r\nThe circumstances of the trial do not make it likely that missingness in the outcome depends on its true value as more participants dropped out of the control group than from the exercise group.\r\n","PN",null,"Some concerns","Some concerns","Considering the fact that the appropriate study population for an analysis of the intention to treat effect is all randomized participants, in this Trial,  less than 95% of the participants in either the exercise group or the control group provided data for this outcome. The authors do state that the drop outs were due to complications after surgery and withdrawal of consent with 9 people dropping out of the study before completing 1 month of exercise training or usual care.\r\nThere is no evidence to prove that the results was not biased by missing outcome data\r\nThere is no considerable difference in the proportions of missing outcome data between the two groups.\r\nThe authors do state that the drop outs were due to complications after surgery and withdrawal of consent, but no mention was made to suggest that the intervention played a part in this withdrawal.\r\nReported reasons for missing outcome data are similar between both groups.\r\nThe circumstances of the trial do not make it likely that missingness in the outcome depends on its true value as more participants dropped out of the control group than from the exercise group.\r\n\r\n",null,null,"N","HRQoL measured using SF36, a validated questionnaire","N","Measurements were made in the same way for both intervention and control ","Y","The person reporting this outcome is the participant and they are aware of the intervention they received. Collation and analysis of the results were most likely arried out by study personnel who were blinded. \r\n“The trial applied central, stratified randomisation securing against selection bias, and blinded outcome assessment and blinded statistical analyses, reducing detection and interpretation bias”","Y","\r\nThe assessment by the participants could have been affected by knowledge of the intervention as it is subjective. Exercise is generally believed to be a beneficial intervention in this patient group and it is possible that participants might have considered their HRQoL would be better if they had the intervention.\r\n","PY",null,"High","High","HRQoL measured using SF36, a validated questionnaire\r\nMeasurements were made in the same way for both intervention and control \r\nThe person reporting this outcome is the participant and they are aware of the intervention they received. Collation and analysis of the results were most likely arried out by study personnel who were blinded. \r\n“The trial applied central, stratified randomisation securing against selection bias, and blinded outcome assessment and blinded statistical analyses, reducing detection and interpretation bias”The assessment by the participants could have been affected by knowledge of the intervention as it is subjective. Exercise is generally believed to be a beneficial intervention in this patient group and it is possible that participants might have considered their HRQoL would be better if they had the intervention.\r\n\r\n",null,null,"Y","Trial registered on clinicaltrials.gov before start of the study  (NCT01558765) with researchers’ pre-specified intentions available in sufficient detail. There is therefore no reason to believe that the reults would not have been analysed in accordance with a pre-specified analysis plan.","N","The authors provided results for all timepoints at which this outcome was assessed within the scope of this article.","N","There is no evidence of multiple eligible analyses for this outcome.","Low","Low","Trial registered on clinicaltrials.gov before start of the study  (NCT01558765) with researchers’ pre-specified intentions available in sufficient detail. There is therefore no reason to believe that the reults would not have been analysed in accordance with a pre-specified analysis plan.\r\nThe authors provided results for all timepoints at which this outcome was assessed within the scope of this article.\r\nThere is no evidence of multiple eligible analyses for this outcome.",null,null,"High","High","The authors state that “Participants were allocated 1:1 to intervention or control using computer-generated allocation sequence with varying block sizes of 8, 6 and 4, concealed to the investigators by central telephone correspondence with the Copenhagen Trial Unit.”\r\n\r\n“There was no evidence of baseline imbalances.” Table 1 shows good balance in patient characteristics between groups\r\nGiven the nature of an exercise-based CR intervention, participants are aware of their intervention and it might therefore not be possible to blind them, their carers, or the people delivering this intervention.\r\n\r\nAlthough te authors do not expressesly mention if there were any deviations from the intended intervention, their CONSORT flow diagram of patients (fig 1 in article) shows that all participants were analysed in their initial intervention group.\r\n\r\n\r\nThe analysis was based on intention to treat using a mixed model with repeated measures (MMRM) and adjusted for the stratification variable of LVEF, ensuring that missing data will not create bias as long as the values are missing at random.25 The MMRM was used for continuous outcomes (both primary and secondary outcomes). This model assumes normally (Gaussian) distributed residuals. However, the residuals were not normally distributed for the primary outcome, and therefore transformed. We used log-transformation, and when log-transformation did not result in normally distributed residuals, we used Box–Cox transformation. In the MMRM we assumed correlation within the individual patient, but no correlation between patients. The fixed effects for the primary outcome were randomisation group, time, interaction between random and time and LVEF.\r\n\r\nConsidering the fact that the appropriate study population for an analysis of the intention to treat effect is all randomized participants, in this Trial,  less than 95% of the participants in either the exercise group or the control group provided data for this outcome. The authors do state that the drop outs were due to complications after surgery and withdrawal of consent with 9 people dropping out of the study before completing 1 month of exercise training or usual care.\r\nThere is no evidence to prove that the results was not biased by missing outcome data\r\nThere is no considerable difference in the proportions of missing outcome data between the two groups.\r\nThe authors do state that the drop outs were due to complications after surgery and withdrawal of consent, but no mention was made to suggest that the intervention played a part in this withdrawal.\r\nReported reasons for missing outcome data are similar between both groups.\r\nThe circumstances of the trial do not make it likely that missingness in the outcome depends on its true value as more participants dropped out of the control group than from the exercise group.\r\n\r\n\r\nHRQoL measured using SF36, a validated questionnaire\r\nMeasurements were made in the same way for both intervention and control \r\nThe person reporting this outcome is the participant and they are aware of the intervention they received. Collation and analysis of the results were most likely arried out by study personnel who were blinded. \r\n“The trial applied central, stratified randomisation securing against selection bias, and blinded outcome assessment and blinded statistical analyses, reducing detection and interpretation bias”The assessment by the participants could have been affected by knowledge of the intervention as it is subjective. Exercise is generally believed to be a beneficial intervention in this patient group and it is possible that participants might have considered their HRQoL would be better if they had the intervention.\r\n\r\n\r\nTrial registered on clinicaltrials.gov before start of the study  (NCT01558765) with researchers’ pre-specified intentions available in sufficient detail. There is therefore no reason to believe that the reults would not have been analysed in accordance with a pre-specified analysis plan.\r\nThe authors provided results for all timepoints at which this outcome was assessed within the scope of this article.\r\nThere is no evidence of multiple eligible analyses for this outcome."]
["2021/02/09 15.08","2_E","LA","Pressler 2016","American Heart Journal vol 182; pp. 44-53","Exercise","No Exercise","HRQoL (PC at maximum follow up)","MD = 1.10 (95% CI -9.7, 11.9)","assignment to intervention (the 'intention-to-treat' effect)","NA",6.2," Journal article(s)","Y","Y","The authors state that “patients were randomly allocated 1:1 according to a computer-generated allocation program code”.\r\nAlthough there was no mention of allocation sequence concealment, the fact that they used a computer-generated program code would prevent the enrolling investigator or the participant from having any knowledge of the forthcoming allocation.\r\n","N","No differences for TG and UC with respect to age, proportion of females, The Society of Thoracic Surgeons mortality risk score, NYHA class, prexisting conditions, and medication were observed (see Table I). ","Low","Low","The authors state that “patients were randomly allocated 1:1 according to a computer-generated allocation program code”.\r\nAlthough there was no mention of allocation sequence concealment, the fact that they used a computer-generated program code would prevent the enrolling investigator or the participant from having any knowledge of the forthcoming allocation.\r\n\r\nNo differences for TG and UC with respect to age, proportion of females, The Society of Thoracic Surgeons mortality risk score, NYHA class, prexisting conditions, and medication were observed (see Table I). ",null,null,"Y","Y","Given the nature of an exercise-based CR intervention, participants are aware of their intervention and it might therefore not be possible to blind them, their carers, or the people delivering this intervention.\r\n","N","Although the authors do not specifically state if there were any deviations from the intended intervention, the flow of participants through the study (Fig 1 of 2016 paper) shows that no participant changed groups during the study and all changes to the intervention were either consistent with the intervention (i.e. drop out due to unrelated causes) or consistent with what could occur outside of the trial context (i.e. drop out due to unwillingness to continue participation).","NA",null,"NA",null,"Y","Data were tested for their distribution and the primary end point and key secondary outcomes were normally distributed; thus it was decided to present data as mean (SD). Baseline differences between groups were analyzed using the Student t test for independent samples for continuous variables and the Fisher exact test for categorical variables. Between-group differences in changes of the primary and secondary end points were analyzed using the Student t test for independent samples. For relevant effect sizes (mean differences between study groups), 95% CIs are presented. Because of the low number of dropouts that were all unrelated to the intervention and the primary intention of the study to evaluate efficacy and safety of exercise, a per-protocol analysis was performed. To account for observed differences in baseline parameters between the study groups, linear regression models using the change in the measure of interest as dependent variable and the study group as well as the baseline value of the measure of interest as independent variable were fit to the data. ","NA",null,"Low","Low","Given the nature of an exercise-based CR intervention, participants are aware of their intervention and it might therefore not be possible to blind them, their carers, or the people delivering this intervention.\r\n\r\nAlthough the authors do not specifically state if there were any deviations from the intended intervention, the flow of participants through the study (Fig 1 of 2016 paper) shows that no participant changed groups during the study and all changes to the intervention were either consistent with the intervention (i.e. drop out due to unrelated causes) or consistent with what could occur outside of the trial context (i.e. drop out due to unwillingness to continue participation).\r\n\r\n\r\nData were tested for their distribution and the primary end point and key secondary outcomes were normally distributed; thus it was decided to present data as mean (SD). Baseline differences between groups were analyzed using the Student t test for independent samples for continuous variables and the Fisher exact test for categorical variables. Between-group differences in changes of the primary and secondary end points were analyzed using the Student t test for independent samples. For relevant effect sizes (mean differences between study groups), 95% CIs are presented. Because of the low number of dropouts that were all unrelated to the intervention and the primary intention of the study to evaluate efficacy and safety of exercise, a per-protocol analysis was performed. To account for observed differences in baseline parameters between the study groups, linear regression models using the change in the measure of interest as dependent variable and the study group as well as the baseline value of the measure of interest as independent variable were fit to the data. \r\n",null,null,"N","Considering the fact that the appropriate study population for an analysis of the intention to treat effect is all randomized participants, in this Trial,  less than 95% of the participants in either the exercise group or the control group provided data for this outcome. ","N","There is no evidence to suggest that the result was not biased by missing outcome data","Y","Although reported reasons for missing outcome data are similar between both groups.There is no considerable difference in the proportions of missing outcome data between the two groups overall with 5 patient data missing from the exercise group and 8 patient data missing from the control group. Most of the missing data was due to death or other health conditions not necessarily related to the intervention. The circumstances of the trial do not make it likely that missingness in the outcome depends on its true value as more participants dropped out of the control group than from the exercise group.","PN",null,"Some concerns","Some concerns","Considering the fact that the appropriate study population for an analysis of the intention to treat effect is all randomized participants, in this Trial,  less than 95% of the participants in either the exercise group or the control group provided data for this outcome, as there were 3 overall drop outs. \r\nThere is no evidence to suggest that the result was not biased by missing outcome data\r\nAlthough reported reasons for missing outcome data are similar between both groups.There is no considerable difference in the proportions of missing outcome data between the two groups overall with 5 patient data missing from the exercise group and 8 patient data missing from the control group. Most of the missing data was due to death or other health conditions not necessarily related to the intervention. The circumstances of the trial do not make it likely that missingness in the outcome depends on its true value as more participants dropped out of the control group than from the exercise group.\r\n",null,null,"N","HRQoL measured using SF36 and KCCQ both of which are validated questionnaires","N","Measurements were made in the same way for both intervention and control ","Y","The person reporting this outcome is the participant and they are aware of the intervention received. Collation and analysis of the results were most likely carried out by study personnel who were blinded to the intervention recived by the study participant.","Y","\r\nThe assessment by the participants could have been affected by knowledge of the intervention as it is subjective. Exercise is generally believed to be a beneficial intervention in this patient group and it is possible that participants might have considered their HRQoL would be better if they had the intervention.","PY",null,"High","High","HRQoL measured using SF36 and KCCQ both of which are validated questionnaires\r\nMeasurements were made in the same way for both intervention and control \r\nThe person reporting this outcome is the participant and they are aware of the intervention received. Collation and analysis of the results were most likely carried out by study personnel who were blinded to the intervention recived by the study participant.The assessment by the participants could have been affected by knowledge of the intervention as it is subjective. Exercise is generally believed to be a beneficial intervention in this patient group and it is possible that participants might have considered their HRQoL would be better if they had the intervention.\r\n",null,null,"Y","The trial was registered on clinicaltrials.gov before start of the study (NCT01935297) with researchers’ pre-specified intentions available in sufficient detail. There is no reason to believe that the data which produced this result was not analysed in accordance with a pre-specified analysis plan.","N","The authors provided results for all timepoints at which this outcome was assessed with all extra analysis intended as exploratory analysis to provide additional information on the group-specific impact of the intervention.","N","The authors reported all results. There is therefore no reason to believe that this result might have been selected from multiple eligible analyses of the data.","Low","Low","The trial was registered on clinicaltrials.gov before start of the study (NCT01935297) with researchers’ pre-specified intentions available in sufficient detail. There is no reason to believe that the data which produced this result was not analysed in accordance with a pre-specified analysis plan.\r\nThe authors provided results for all timepoints at which this outcome was assessed with all extra analysis intended as exploratory analysis to provide additional information on the group-specific impact of the intervention.\r\nThe authors reported all results. There is therefore no reason to believe that this result might have been selected from multiple eligible analyses of the data.",null,null,"High","High","The authors state that “patients were randomly allocated 1:1 according to a computer-generated allocation program code”.\r\nAlthough there was no mention of allocation sequence concealment, the fact that they used a computer-generated program code would prevent the enrolling investigator or the participant from having any knowledge of the forthcoming allocation.\r\n\r\nNo differences for TG and UC with respect to age, proportion of females, The Society of Thoracic Surgeons mortality risk score, NYHA class, prexisting conditions, and medication were observed (see Table I). \r\nGiven the nature of an exercise-based CR intervention, participants are aware of their intervention and it might therefore not be possible to blind them, their carers, or the people delivering this intervention.\r\n\r\nAlthough the authors do not specifically state if there were any deviations from the intended intervention, the flow of participants through the study (Fig 1 of 2016 paper) shows that no participant changed groups during the study and all changes to the intervention were either consistent with the intervention (i.e. drop out due to unrelated causes) or consistent with what could occur outside of the trial context (i.e. drop out due to unwillingness to continue participation).\r\n\r\n\r\nData were tested for their distribution and the primary end point and key secondary outcomes were normally distributed; thus it was decided to present data as mean (SD). Baseline differences between groups were analyzed using the Student t test for independent samples for continuous variables and the Fisher exact test for categorical variables. Between-group differences in changes of the primary and secondary end points were analyzed using the Student t test for independent samples. For relevant effect sizes (mean differences between study groups), 95% CIs are presented. Because of the low number of dropouts that were all unrelated to the intervention and the primary intention of the study to evaluate efficacy and safety of exercise, a per-protocol analysis was performed. To account for observed differences in baseline parameters between the study groups, linear regression models using the change in the measure of interest as dependent variable and the study group as well as the baseline value of the measure of interest as independent variable were fit to the data. \r\n\r\nConsidering the fact that the appropriate study population for an analysis of the intention to treat effect is all randomized participants, in this Trial,  less than 95% of the participants in either the exercise group or the control group provided data for this outcome, as there were 3 overall drop outs. \r\nThere is no evidence to suggest that the result was not biased by missing outcome data\r\nAlthough reported reasons for missing outcome data are similar between both groups.There is no considerable difference in the proportions of missing outcome data between the two groups overall with 5 patient data missing from the exercise group and 8 patient data missing from the control group. Most of the missing data was due to death or other health conditions not necessarily related to the intervention. The circumstances of the trial do not make it likely that missingness in the outcome depends on its true value as more participants dropped out of the control group than from the exercise group.\r\n\r\nHRQoL measured using SF36 and KCCQ both of which are validated questionnaires\r\nMeasurements were made in the same way for both intervention and control \r\nThe person reporting this outcome is the participant and they are aware of the intervention received. Collation and analysis of the results were most likely carried out by study personnel who were blinded to the intervention recived by the study participant.The assessment by the participants could have been affected by knowledge of the intervention as it is subjective. Exercise is generally believed to be a beneficial intervention in this patient group and it is possible that participants might have considered their HRQoL would be better if they had the intervention.\r\n\r\nThe trial was registered on clinicaltrials.gov before start of the study (NCT01935297) with researchers’ pre-specified intentions available in sufficient detail. There is no reason to believe that the data which produced this result was not analysed in accordance with a pre-specified analysis plan.\r\nThe authors provided results for all timepoints at which this outcome was assessed with all extra analysis intended as exploratory analysis to provide additional information on the group-specific impact of the intervention.\r\nThe authors reported all results. There is therefore no reason to believe that this result might have been selected from multiple eligible analyses of the data."]
["2021/02/09 17.30","4_A","MHB","Sibilitz 2016","Heart 2016; 102; 1995-2003","Exercise","No Exercise","All-Cause Hospitalisation","RR = 2.72 (95% CI 0.11, 65.56)","assignment to intervention (the 'intention-to-treat' effect)","NA",100," Journal article(s); Trial protocol","Y","Y","Patients were allocated to intervention or control using computer-generated allocation sequence with varying block sizes of 8, 6, or 4, concealed to the investigators by central telephone correspondence with the Copenhagen Trial Unit.","N","see table 1","Low","Low","Patients were allocated to intervention or control using computer-generated allocation sequence with varying block sizes of 8, 6, or 4, concealed to the investigators by central telephone correspondence with the Copenhagen Trial Unit.\r\nsee table 1",null,null,"Y","Y","\"Blinding of clinicians and participants is impossible in a rehabilitation trial.\"","PN","\"A major concern is that the control group might have received different interventions at the local hospitals, which might diminish the impact of our experimental intervention.\" p. 2002","NA",null,"NA",null,"PY","Count data only; just one event observed","NA",null,"Low","Low","\"Blinding of clinicians and participants is impossible in a rehabilitation trial.\"\r\n\"A major concern is that the control group might have received different interventions at the local hospitals, which might diminish the impact of our experimental intervention.\" p. 2002\r\n\r\n\r\nCount data only; just one event observed\r\n",null,null,"NI","There is no information as to whether all-cause hospitalisation data were sought for all participants","PN","1 rehospitalisation out of 147 heart valve surgery patients over six months seems very low. ","PY","\"dropouts were due to complications after surgery\" which may well have involved rehospitalisation","PY",null,"High","High","There is no information as to whether all-cause hospitalisation data were sought for all participants\r\n1 rehospitalisation out of 147 heart valve surgery patients over six months seems very low. \r\n\"dropouts were due to complications after surgery\" which may well have involved rehospitalisation\r\n",null,null,"PY","Reporting adverse events is probably a substantially different and less comprehensive measurement method compared to other methods of measuring all-cause hospitalisation","PN","It is possible but unlikely that adverse events could have been investigated differently in the intervention group because assignment was not blinded","NA",null,"NA",null,"NA",null,"High","High","Reporting adverse events is probably a substantially different and less comprehensive measurement method compared to other methods of measuring all-cause hospitalisation\r\nIt is possible but unlikely that adverse events could have been investigated differently in the intervention group because assignment was not blinded\r\n\r\n\r\n",null,null,"N","The protocol does not specify all-cause hospitalisation as a primary or secondary outcome, and does not state how adverse events will be defined or analysed.","PN","All-cause hospitalisation was not mentioned as an outcome in the study protocol and definitions of adverse events were not provided","PN","only one event was observed","Some concerns","Some concerns","The protocol does not specify all-cause hospitalisation as a primary or secondary outcome, and does not state how adverse events will be defined or analysed.\r\nAll-cause hospitalisation was not mentioned as an outcome in the study protocol and definitions of adverse events were not provided\r\nonly one event was observed",null,null,"High","High","Patients were allocated to intervention or control using computer-generated allocation sequence with varying block sizes of 8, 6, or 4, concealed to the investigators by central telephone correspondence with the Copenhagen Trial Unit.\r\nsee table 1\r\n\"Blinding of clinicians and participants is impossible in a rehabilitation trial.\"\r\n\"A major concern is that the control group might have received different interventions at the local hospitals, which might diminish the impact of our experimental intervention.\" p. 2002\r\n\r\n\r\nCount data only; just one event observed\r\n\r\nThere is no information as to whether all-cause hospitalisation data were sought for all participants\r\n1 rehospitalisation out of 147 heart valve surgery patients over six months seems very low. \r\n\"dropouts were due to complications after surgery\" which may well have involved rehospitalisation\r\n\r\nReporting adverse events is probably a substantially different and less comprehensive measurement method compared to other methods of measuring all-cause hospitalisation\r\nIt is possible but unlikely that adverse events could have been investigated differently in the intervention group because assignment was not blinded\r\n\r\n\r\n\r\nThe protocol does not specify all-cause hospitalisation as a primary or secondary outcome, and does not state how adverse events will be defined or analysed.\r\nAll-cause hospitalisation was not mentioned as an outcome in the study protocol and definitions of adverse events were not provided\r\nonly one event was observed"]
["2021/02/09 17.47","4_B","MHB","Sibilitz 2016","Heart 2016; 102: 1995-2003","Exercise","No Exercise","HRQoL (MC End of Intervention)","MD = 0.8 (95% CI -2.46, 4.06)","assignment to intervention (the 'intention-to-treat' effect)","NA",78.2," Journal article(s); Trial protocol","Y","Y","Patients were allocated to intervention or control using computer-generated allocation sequence with varying block sizes of 8, 6, or 4, concealed to the investigators by central telephone correspondence with the Copenhagen Trial Unit.","N","see Table 1","Low","Low","Patients were allocated to intervention or control using computer-generated allocation sequence with varying block sizes of 8, 6, or 4, concealed to the investigators by central telephone correspondence with the Copenhagen Trial Unit.\r\nsee Table 1",null,null,"Y","Y","\"Blinding of clinicians and participants is impossible in a rehabilitation trial.\"","PN","\"A major concern is that the control group might have received different interventions at the local hospitals, which might diminish the impact of our experimental intervention.\" p. 2002","NA",null,"NA",null,"Y","The analysis was based on intention to treat using a mixed model with repeated measures (MMRM) and adjusted for the stratification variable","NA",null,"Low","Low","\"Blinding of clinicians and participants is impossible in a rehabilitation trial.\"\r\n\"A major concern is that the control group might have received different interventions at the local hospitals, which might diminish the impact of our experimental intervention.\" p. 2002\r\n\r\n\r\nThe analysis was based on intention to treat using a mixed model with repeated measures (MMRM) and adjusted for the stratification variable\r\n",null,null,"Y","Data available for this outcome for 65/72 intervention and 61/75 control group","NA",null,"NA",null,"NA",null,"Low","Low","Data available for this outcome for 65/72 intervention and 61/75 control group\r\n\r\n\r\n",null,null,"N","mental health was measured by SF-36, Mental Component Scale","PN","same validated scale used in both groups","Y","self-reported by participants aware of their allocation","PY","possible, but unlikely as there was no difference between groups","PN",null,"Some concerns","Some concerns","mental health was measured by SF-36, Mental Component Scale\r\nsame validated scale used in both groups\r\nself-reported by participants aware of their allocation\r\npossible, but unlikely as there was no difference between groups\r\n",null,null,"PY","The analysis seems in accordance with the analysis implied by the protocol, although a detailed pre-specified analysis plan was not identified.","PN","The outcome measurements in the report were specified in the protocol and results are reported for all time points recorded.","PN","\"No interaction between intervention and time was observedfor SF-36 MCSbetween groups at 6 months\"","Low","Low","The analysis seems in accordance with the analysis implied by the protocol, although a detailed pre-specified analysis plan was not identified.\r\nThe outcome measurements in the report were specified in the protocol and results are reported for all time points recorded.\r\n\"No interaction between intervention and time was observedfor SF-36 MCSbetween groups at 6 months\"",null,null,"Some concerns","Some concerns","Patients were allocated to intervention or control using computer-generated allocation sequence with varying block sizes of 8, 6, or 4, concealed to the investigators by central telephone correspondence with the Copenhagen Trial Unit.\r\nsee Table 1\r\n\"Blinding of clinicians and participants is impossible in a rehabilitation trial.\"\r\n\"A major concern is that the control group might have received different interventions at the local hospitals, which might diminish the impact of our experimental intervention.\" p. 2002\r\n\r\n\r\nThe analysis was based on intention to treat using a mixed model with repeated measures (MMRM) and adjusted for the stratification variable\r\n\r\nData available for this outcome for 65/72 intervention and 61/75 control group\r\n\r\n\r\n\r\nmental health was measured by SF-36, Mental Component Scale\r\nsame validated scale used in both groups\r\nself-reported by participants aware of their allocation\r\npossible, but unlikely as there was no difference between groups\r\n\r\nThe analysis seems in accordance with the analysis implied by the protocol, although a detailed pre-specified analysis plan was not identified.\r\nThe outcome measurements in the report were specified in the protocol and results are reported for all time points recorded.\r\n\"No interaction between intervention and time was observedfor SF-36 MCSbetween groups at 6 months\""]
["2021/02/09 18.03","4_C","MHB","Sibilitz 2016","Heart 2016; 102: 1995-2003","Exercise","No Exercise","HRQoL (PC End of Intervention)","MD = -0.6 (95% CI -3.43, 2.23)","assignment to intervention (the 'intention-to-treat' effect)","NA",57.8," Journal article(s); Trial protocol","Y","Y","Patients were allocated to intervention or control using computer-generated allocation sequence with varying block sizes of 8, 6, or 4, concealed to the investigators by central telephone correspondence with the Copenhagen Trial Unit.","N","see Table 1","Low","Low","Patients were allocated to intervention or control using computer-generated allocation sequence with varying block sizes of 8, 6, or 4, concealed to the investigators by central telephone correspondence with the Copenhagen Trial Unit.\r\nsee Table 1",null,null,"Y","Y","\"Blinding of clinicians and participants is impossible in a rehabilitation trial.\"","PN","\"A major concern is that the control group might have received different interventions at the local hospitals, which might diminish the impact of our experimental intervention.\" p. 2003","NA",null,"NA",null,"Y","The analysis was based on intention to treat using a mixed model with repeated measures (MMRM) and adjusted for the stratification variable","NA",null,"Low","Low","\"Blinding of clinicians and participants is impossible in a rehabilitation trial.\"\r\n\"A major concern is that the control group might have received different interventions at the local hospitals, which might diminish the impact of our experimental intervention.\" p. 2003\r\n\r\n\r\nThe analysis was based on intention to treat using a mixed model with repeated measures (MMRM) and adjusted for the stratification variable\r\n",null,null,"Y","Data were available for 65/72 treated and 61/75 controls for this outcome","NA",null,"NA",null,"NA",null,"Low","Low","Data were available for 65/72 treated and 61/75 controls for this outcome\r\n\r\n\r\n",null,null,"N","Physical HRQoL was measured with the Physical Component Scale of SF-36","PN","same validated scale used in both groups","Y","self-reported by participants aware of their allocation","PY","possible, but unlikely as there was no difference between groups","PN",null,"Some concerns","Some concerns","Physical HRQoL was measured with the Physical Component Scale of SF-36\r\nsame validated scale used in both groups\r\nself-reported by participants aware of their allocation\r\npossible, but unlikely as there was no difference between groups\r\n",null,null,"PY","The analysis seems in accordance with the analysis implied by the protocol, although a detailed pre-specified analysis plan was not identified and this particular component of SF-36 was not mentioned in the protocol.","PN","The outcome measurements are reported for 1, 4, and 6 months follow up.","PN","There is no statistically significant difference between groups in the reported outcome.","Low","Low","The analysis seems in accordance with the analysis implied by the protocol, although a detailed pre-specified analysis plan was not identified and this particular component of SF-36 was not mentioned in the protocol.\r\nThe outcome measurements are reported for 1, 4, and 6 months follow up.\r\nThere is no statistically significant difference between groups in the reported outcome.",null,null,"Some concerns","Some concerns","Patients were allocated to intervention or control using computer-generated allocation sequence with varying block sizes of 8, 6, or 4, concealed to the investigators by central telephone correspondence with the Copenhagen Trial Unit.\r\nsee Table 1\r\n\"Blinding of clinicians and participants is impossible in a rehabilitation trial.\"\r\n\"A major concern is that the control group might have received different interventions at the local hospitals, which might diminish the impact of our experimental intervention.\" p. 2003\r\n\r\n\r\nThe analysis was based on intention to treat using a mixed model with repeated measures (MMRM) and adjusted for the stratification variable\r\n\r\nData were available for 65/72 treated and 61/75 controls for this outcome\r\n\r\n\r\n\r\nPhysical HRQoL was measured with the Physical Component Scale of SF-36\r\nsame validated scale used in both groups\r\nself-reported by participants aware of their allocation\r\npossible, but unlikely as there was no difference between groups\r\n\r\nThe analysis seems in accordance with the analysis implied by the protocol, although a detailed pre-specified analysis plan was not identified and this particular component of SF-36 was not mentioned in the protocol.\r\nThe outcome measurements are reported for 1, 4, and 6 months follow up.\r\nThere is no statistically significant difference between groups in the reported outcome."]
["2021/02/09 18.26","4_D","MHB","Sibilitz 2016","Heart 2016; 102: 1995-2003","Exercise","No Exercise","HRQoL (MC Maximum Follow-up)","MD = -1.5 (95% CI -4.93, 1.93)","assignment to intervention (the 'intention-to-treat' effect)","NA",90," Journal article(s); Trial protocol","Y","Y","Patients were allocated to intervention or control using computer-generated allocation sequence with varying block sizes of 8, 6, or 4, concealed to the investigators by central telephone correspondence with the Copenhagen Trial Unit.","N","see Table 1","Low","Low","Patients were allocated to intervention or control using computer-generated allocation sequence with varying block sizes of 8, 6, or 4, concealed to the investigators by central telephone correspondence with the Copenhagen Trial Unit.\r\nsee Table 1",null,null,"Y","Y","\"Blinding of clinicians and participants is impossible in a rehabilitation trial.\"","PN","\"A major concern is that the control group might have received different interventions at the local hospitals, which might diminish the impact of our experimental intervention.\" p. 2004","NA",null,"NA",null,"Y","\"The analysis was based on intention to treat using a mixed model with repeated measures (MMRM) and adjusted for the stratification variable\"","NA",null,"Low","Low","\"Blinding of clinicians and participants is impossible in a rehabilitation trial.\"\r\n\"A major concern is that the control group might have received different interventions at the local hospitals, which might diminish the impact of our experimental intervention.\" p. 2004\r\n\r\n\r\n\"The analysis was based on intention to treat using a mixed model with repeated measures (MMRM) and adjusted for the stratification variable\"\r\n",null,null,"PY","at 6 months data were available for 64/72 treated and 58/75 control, which seems reasonable for this type of intervention and length of follow up","NA",null,"NA",null,"NA",null,"Low","Low","at 6 months data were available for 64/72 treated and 58/75 control, which seems reasonable for this type of intervention and length of follow up\r\n\r\n\r\n",null,null,"N","mental health was measured by SF-36, Mental Component Scale","PN","same validated scale used in both groups","Y","self-reported by participants aware of their allocation","PY","possible, but unlikely as there was no difference between groups","PN",null,"Some concerns","Some concerns","mental health was measured by SF-36, Mental Component Scale\r\nsame validated scale used in both groups\r\nself-reported by participants aware of their allocation\r\npossible, but unlikely as there was no difference between groups\r\n",null,null,"PY","The analysis seems in accordance with the analysis implied by the protocol, although a detailed pre-specified analysis plan was not identified.","PN","The outcome measurements in the report were specified in the protocol and results are reported for all time points recorded.","PN","There is no statistically significant difference between groups in the reported outcome.","Low","Low","The analysis seems in accordance with the analysis implied by the protocol, although a detailed pre-specified analysis plan was not identified.\r\nThe outcome measurements in the report were specified in the protocol and results are reported for all time points recorded.\r\nThere is no statistically significant difference between groups in the reported outcome.",null,null,"Some concerns","Some concerns","Patients were allocated to intervention or control using computer-generated allocation sequence with varying block sizes of 8, 6, or 4, concealed to the investigators by central telephone correspondence with the Copenhagen Trial Unit.\r\nsee Table 1\r\n\"Blinding of clinicians and participants is impossible in a rehabilitation trial.\"\r\n\"A major concern is that the control group might have received different interventions at the local hospitals, which might diminish the impact of our experimental intervention.\" p. 2004\r\n\r\n\r\n\"The analysis was based on intention to treat using a mixed model with repeated measures (MMRM) and adjusted for the stratification variable\"\r\n\r\nat 6 months data were available for 64/72 treated and 58/75 control, which seems reasonable for this type of intervention and length of follow up\r\n\r\n\r\n\r\nmental health was measured by SF-36, Mental Component Scale\r\nsame validated scale used in both groups\r\nself-reported by participants aware of their allocation\r\npossible, but unlikely as there was no difference between groups\r\n\r\nThe analysis seems in accordance with the analysis implied by the protocol, although a detailed pre-specified analysis plan was not identified.\r\nThe outcome measurements in the report were specified in the protocol and results are reported for all time points recorded.\r\nThere is no statistically significant difference between groups in the reported outcome."]
["2021/02/09 18.42","4_E","MHB","Sibilitz 2016","Heart 2016; 102: 1995-2003","Exercise","No Exercise","HRQoL (PC Maximum Follow-up)","MD = -1 (95% CI -3.79, 1.79)","assignment to intervention (the 'intention-to-treat' effect)","NA",93.8," Journal article(s); Trial protocol","Y","Y","Patients were allocated to intervention or control using computer-generated allocation sequence with varying block sizes of 8, 6, or 4, concealed to the investigators by central telephone correspondence with the Copenhagen Trial Unit.","N","see Table 1","Low","Low","Patients were allocated to intervention or control using computer-generated allocation sequence with varying block sizes of 8, 6, or 4, concealed to the investigators by central telephone correspondence with the Copenhagen Trial Unit.\r\nsee Table 1",null,null,"Y","Y","\"Blinding of clinicians and participants is impossible in a rehabilitation trial.\"","PN","\"A major concern is that the control group might have received different interventions at the local hospitals, which might diminish the impact of our experimental intervention.\" p. 2005","NA",null,"NA",null,"Y","The analysis was based on intention to treat using a mixed model with repeated measures (MMRM) and adjusted for the stratification variable","NA",null,"Low","Low","\"Blinding of clinicians and participants is impossible in a rehabilitation trial.\"\r\n\"A major concern is that the control group might have received different interventions at the local hospitals, which might diminish the impact of our experimental intervention.\" p. 2005\r\n\r\n\r\nThe analysis was based on intention to treat using a mixed model with repeated measures (MMRM) and adjusted for the stratification variable\r\n",null,null,"Y","Data were available for 64/72 treated and 58/75 control, which seems reasonable for this type of intervention","NA",null,"NA",null,"NA",null,"Low","Low","Data were available for 64/72 treated and 58/75 control, which seems reasonable for this type of intervention\r\n\r\n\r\n",null,null,"N","Physical HRQoL was measured with the Physical Component Scale of SF-36","PN","same validated scale used in both groups","Y","self-reported by participants aware of their allocation","PY","possible, but unlikely as there was no difference between groups","PN",null,"Some concerns","Some concerns","Physical HRQoL was measured with the Physical Component Scale of SF-36\r\nsame validated scale used in both groups\r\nself-reported by participants aware of their allocation\r\npossible, but unlikely as there was no difference between groups\r\n",null,null,"PY","The analysis seems in accordance with the analysis implied by the protocol, although a detailed pre-specified analysis plan was not identified and this particular component of SF-36 was not mentioned in the protocol.","PN","results are reported for all time points recorded.","PN","There is no statistically significant difference between groups in the reported outcome.","Low","Low","The analysis seems in accordance with the analysis implied by the protocol, although a detailed pre-specified analysis plan was not identified and this particular component of SF-36 was not mentioned in the protocol.\r\nresults are reported for all time points recorded.\r\nThere is no statistically significant difference between groups in the reported outcome.",null,null,"Some concerns","Some concerns","Patients were allocated to intervention or control using computer-generated allocation sequence with varying block sizes of 8, 6, or 4, concealed to the investigators by central telephone correspondence with the Copenhagen Trial Unit.\r\nsee Table 1\r\n\"Blinding of clinicians and participants is impossible in a rehabilitation trial.\"\r\n\"A major concern is that the control group might have received different interventions at the local hospitals, which might diminish the impact of our experimental intervention.\" p. 2005\r\n\r\n\r\nThe analysis was based on intention to treat using a mixed model with repeated measures (MMRM) and adjusted for the stratification variable\r\n\r\nData were available for 64/72 treated and 58/75 control, which seems reasonable for this type of intervention\r\n\r\n\r\n\r\nPhysical HRQoL was measured with the Physical Component Scale of SF-36\r\nsame validated scale used in both groups\r\nself-reported by participants aware of their allocation\r\npossible, but unlikely as there was no difference between groups\r\n\r\nThe analysis seems in accordance with the analysis implied by the protocol, although a detailed pre-specified analysis plan was not identified and this particular component of SF-36 was not mentioned in the protocol.\r\nresults are reported for all time points recorded.\r\nThere is no statistically significant difference between groups in the reported outcome."]

{"sheet":"Summary","index":2,"n_rows":17,"n_cols":27,"rows_kept":17,"cut":false,"hidden":false,"merged":[]}
["Unique ID","Reviewer","Study ID","Reference","Experimental","Comparator","Outcome","Result","Aim","Effect of adhering to intervention?","Weight","Randomization process","Deviations from intended interventions","Mising outcome data","Measurement of the outcome","Selection of the reported result","Overall Bias",null,null,null,null,"Randomization process","Deviations from intended interventions","Mising outcome data","Measurement of the outcome","Selection of the reported result","Overall Bias"]
["1_A","LA","Lin 2004","Chinese Journal of Clinical Rehabilitation","Exercise ","No Exercise","All-cause Mortality","RR =4.46 (95% CI 0.22, 90.78)","assignment to intervention (the 'intention-to-treat' effect)","NA",9.9,"Some concerns","Some concerns","High","Low","Low","High",null,null,null,"Assignment to intervention (the 'intention-to-treat' effect)"]
["2_A","LA","Pressler 2018","European Journal of Preventive Cardiology","Exercise","No Exercise","All-cause Mortality","RR = 0.43 (95% CI 0.10, 1.85) (results from fig 1 in article)","assignment to intervention (the 'intention-to-treat' effect)","NA",90.1,"Low","Low","Low","Low","Low","Low",null,null,null,"Total number of study = 16"]
["3_A","LA","Sibilitz 2016","Heart 2016; 102: 1995-2003","Exercise","No Exercise","All-cause Hospitalisation","RR = 2.72 (95% CI 0.11, 65.56)","assignment to intervention (the 'intention-to-treat' effect)","NA",100,"Low","Low","Some concerns","Low","Low","Some concerns",null,null,null,"Low risk",99,99,46.5,19.600000000000001,90.2,8.8000000000000007]
["2_B","LA","Pressler 2016","American Heart Journal vol 182; pp. 44-53","Exercise","No Exercise","HRQoL (MC at end of intervention)","MD = 3 (95% CI -3.16, 9.16)","assignment to intervention (the 'intention-to-treat' effect)","NA",21.8,"Low","Low","Low","High","Low","High",null,null,null,"Some concerns",1,1,42.8,31.4,9.8000000000000007,41.2]
["3_B","LA","Sibilitz 2016","Heart 2016; 102: 1995-2003","Exercise","No Exercise","HRQoL (MC at end of intervention)","MD = 0.80 (95% CI -2.46, 4.06)","assignment to intervention (the 'intention-to-treat' effect)","NA",78.2,"Low","Low","Some concerns","High","Low","High",null,null,null,"High risk",0,0,10.8,49,0,50]
["2_C","LA","Pressler 2016","American Heart Journal vol 182; pp. 44-53","Exercise","No Exercise","HRQoL (PC at end of intervention)","MD = 7.9 (95% CI 0.73, 15.07)","assignment to intervention (the 'intention-to-treat' effect)","NA",42.2,"Low","Low","Low","High","Low","High",null,null,null,"Adhering to intervention (the 'per-protocol' effect)"]
["3_C","LA","Sibilitz 2016","Heart 2016; 102: 1995-2003","Exercise","No Exercise","HRQoL (PC at end of intervention)","MD = -0.60 (95% CI -3.43, 2.23)","assignment to intervention (the 'intention-to-treat' effect)","NA",57.8,"Low","Low","Some concerns","High","Low","High",null,null,null,"Total number of study = 0"]
["2_D","LA","Pressler 2016","American Heart Journal vol 182; pp. 44-53","Exercise","No Exercise","HRQoL (MC at maximum follow up)","MD = -1 (95% CI -11.27, 9.27)","assignment to intervention (the 'intention-to-treat' effect)","NA",10,"Low","Low","Some concerns","High","Low","High",null,null,null,"Low risk"]
["3_D","LA","Sibilitz 2016","Heart 2016; 102: 1995-2003","Exercise","No Exercise","HRQoL (MC at maximum follow up)","MD = -1.5 (95% CI -4.93, 1.93)","assignment to intervention (the 'intention-to-treat' effect)","NA",90,"Low","Low","Some concerns","High","Low","High",null,null,null,"Some concerns"]
["3_E","LA","Sibilitz 2016","Heart 2016; 102: 1995-2003","Exercise","No Exercise","HRQoL (PC at maximum follow up)","MD = -1 (95% CI -3.79, 1.79)","assignment to intervention (the 'intention-to-treat' effect)","NA",93.8,"Low","Low","Some concerns","High","Low","High",null,null,null,"High risk"]
["2_E","LA","Pressler 2016","American Heart Journal vol 182; pp. 44-53","Exercise","No Exercise","HRQoL (PC at maximum follow up)","MD = 1.10 (95% CI -9.7, 11.9)","assignment to intervention (the 'intention-to-treat' effect)","NA",6.2,"Low","Low","Some concerns","High","Low","High"]
["4_A","MHB","Sibilitz 2016","Heart 2016; 102; 1995-2003","Exercise","No Exercise","All-Cause Hospitalisation","RR = 2.72 (95% CI 0.11, 65.56)","assignment to intervention (the 'intention-to-treat' effect)","NA",100,"Low","Low","High","High","Some concerns","High"]
["4_B","MHB","Sibilitz 2016","Heart 2016; 102: 1995-2003","Exercise","No Exercise","HRQoL (MC End of Intervention)","MD = 0.8 (95% CI -2.46, 4.06)","assignment to intervention (the 'intention-to-treat' effect)","NA",78.2,"Low","Low","Low","Some concerns","Low","Some concerns"]
["4_C","MHB","Sibilitz 2016","Heart 2016; 102: 1995-2003","Exercise","No Exercise","HRQoL (PC End of Intervention)","MD = -0.6 (95% CI -3.43, 2.23)","assignment to intervention (the 'intention-to-treat' effect)","NA",57.8,"Low","Low","Low","Some concerns","Low","Some concerns"]
["4_D","MHB","Sibilitz 2016","Heart 2016; 102: 1995-2003","Exercise","No Exercise","HRQoL (MC Maximum Follow-up)","MD = -1.5 (95% CI -4.93, 1.93)","assignment to intervention (the 'intention-to-treat' effect)","NA",90,"Low","Low","Low","Some concerns","Low","Some concerns"]
["4_E","MHB","Sibilitz 2016","Heart 2016; 102: 1995-2003","Exercise","No Exercise","HRQoL (PC Maximum Follow-up)","MD = -1 (95% CI -3.79, 1.79)","assignment to intervention (the 'intention-to-treat' effect)","NA",93.8,"Low","Low","Low","Some concerns","Low","Some concerns"]

{"sheet":"Figure (ITT)","index":3,"n_rows":17,"n_cols":16,"rows_kept":17,"cut":false,"hidden":false,"merged":[]}
["Intention-to-treat","Unique ID","Study ID","Experimental","Comparator","Outcome","Weight","D1","D2","D3","D4","D5","Overall"]
[null,"1_A","Lin 2004","Exercise ","No Exercise","All-cause Mortality",9.9,null,null,null,null,null,null,null,null,"Low risk"]
[null,"2_A","Pressler 2018","Exercise","No Exercise","All-cause Mortality",90.1,null,null,null,null,null,null,null,null,"Some concerns"]
[null,"3_A","Sibilitz 2016","Exercise","No Exercise","All-cause Hospitalisation",100,null,null,null,null,null,null,null,null,"High risk"]
[null,"2_B","Pressler 2016","Exercise","No Exercise","HRQoL (MC at end of intervention)",21.8]
[null,"3_B","Sibilitz 2016","Exercise","No Exercise","HRQoL (MC at end of intervention)",78.2,null,null,null,null,null,null,null,"D1","Randomisation process"]
[null,"2_C","Pressler 2016","Exercise","No Exercise","HRQoL (PC at end of intervention)",42.2,null,null,null,null,null,null,null,"D2","Deviations from the intended interventions"]
[null,"3_C","Sibilitz 2016","Exercise","No Exercise","HRQoL (PC at end of intervention)",57.8,null,null,null,null,null,null,null,"D3","Missing outcome data"]
[null,"2_D","Pressler 2016","Exercise","No Exercise","HRQoL (MC at maximum follow up)",10,null,null,null,null,null,null,null,"D4","Measurement of the outcome"]
[null,"3_D","Sibilitz 2016","Exercise","No Exercise","HRQoL (MC at maximum follow up)",90,null,null,null,null,null,null,null,"D5","Selection of the reported result"]
[null,"3_E","Sibilitz 2016","Exercise","No Exercise","HRQoL (PC at maximum follow up)",93.8]
[null,"2_E","Pressler 2016","Exercise","No Exercise","HRQoL (PC at maximum follow up)",6.2]
[null,"4_A","Sibilitz 2016","Exercise","No Exercise","All-Cause Hospitalisation",100]
[null,"4_B","Sibilitz 2016","Exercise","No Exercise","HRQoL (MC End of Intervention)",78.2]
[null,"4_C","Sibilitz 2016","Exercise","No Exercise","HRQoL (PC End of Intervention)",57.8]
[null,"4_D","Sibilitz 2016","Exercise","No Exercise","HRQoL (MC Maximum Follow-up)",90]
[null,"4_E","Sibilitz 2016","Exercise","No Exercise","HRQoL (PC Maximum Follow-up)",93.8]

{"sheet":"Figure (PP)","index":4,"n_rows":1,"n_cols":13,"rows_kept":1,"cut":false,"hidden":false,"merged":[]}
["Per-protocol","Unique ID","Study ID","Experimental","Comparator","Outcome","Weight","D1","D2","D3","D4","D5","Overall"]

{"sheet":"Print 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["Unique ID","1_A","Study ID","Lin 2004","Assessor","LA"]
["Ref or Label","Chinese Journal of Clinical Rehabilitation","Aim","assignment to intervention (the 'intention-to-treat' effect)\n\n"]
["Experimental","Exercise ","Comparator","No Exercise","Source"," Journal article(s)"]
["Outcome","All-cause Mortality","Results","RR =4.46 (95% CI 0.22, 90.78)","Weight",9.9]
["Domain","Signalling question",null,null,"Response","Comments"]
["Bias arising from the randomization process","1.1 Was the allocation sequence random?",null,null,"NI","The only information provided about randomization is a statement stating that the patients were randomly divided into experimental or control groups.\r\n\r\nThere is no reference to concealment of allocation sequence. "]
[null,"1.2 Was the allocation sequence concealed until participants were enrolled and assigned to interventions?",null,null,"NI"]
[null,"1.3 Did baseline differences between intervention groups suggest a problem with the randomization process?",null,null,"N","There seemed to be no imbalance between the two study groups according to baseline characteristics."]
[null,"Risk of bias judgement",null,null,"Some concerns"]
["Bias due to deviations from intended interventions","2.1.Were participants aware of their assigned intervention during the trial?",null,null,"Y","Given the nature of an exercise-based CR intervention, participants are aware of their intervention and it might therefore not be possible to blind them, their carers, or the people delivering this intervention."]
[null,"2.2.Were carers and people delivering the interventions aware of participants' assigned intervention during the trial?",null,null,"Y"]
[null,"2.3. If Y/PY/NI to 2.1 or 2.2: Were there deviations from the intended intervention that arose because of the experimental context?",null,null,"NI","The authors did not provide any information to help us ascertain whether people may or may not have deviated from the intended intervention."]
[null,"2.4 If Y/PY to 2.3: Were these deviations likely to have affected the outcome?",null,null,"NA"]
[null,"2.5. If Y/PY/NI to 2.4: Were these deviations from intended intervention balanced between groups?",null,null,"NA"]
[null,"2.6 Was an appropriate analysis used to estimate the effect of assignment to intervention?",null,null,"NI","The authors did not state if any analysis was carried out to estimate the effect of assignment to the intervention."]
[null,"2.7 If N/PN/NI to 2.6: Was there potential for a substantial impact (on the result) of the failure to analyse participants in the group to which they were randomized?",null,null,"PN","There is no reason to believe that participants were excluded from the analysis or assessed in the wrong intervention group."]
[null,"Risk of bias judgement",null,null,"Some concerns"]
["Bias due to missing outcome data","3.1 Were data for this outcome available for all, or nearly all, participants randomized?",null,null,"PN","The authors reported that only participants who did not drop out and were not lost to follow-up were included in analysis."]
[null,"3.2 If N/PN/NI to 3.1: Is there evidence that result was not biased by missing outcome data?",null,null,"PN"," The authors state that they used available case analysis but this does not account for missing data."]
[null,"3.3 If N/PN to 3.2: Could missingness in the outcome depend on its true value?",null,null,"PY","Eventhough the outcome is mortality and it is centrally registered, because the trial only included participants who were not lost to follow up, this might have affected the number of recorded deaths by this trial. The authors do not provide enough information to allow us further assess whether or not the missingness depended on its true value"]
[null,"3.4 If Y/PY/NI to 3.3: Is it likely that missingness in the outcome depended on its true value?",null,null,"PY"]
[null,"Risk of bias judgement",null,null,"High","The authors reported that only participants who did not drop out and were not lost to follow-up were included in analysis.\n The authors state that they used available case analysis but this does not account for missing data.\nEventhough the outcome is mortality and it is centrally registered, because the trial only included participants who were not lost to follow up, this might have affected the number of recorded deaths by this trial. The authors do not provide enough information to allow us further assess whether or not the missingness depended on its true value\n"]
["Bias in measurement of the outcome","4.1 Was the method of measuring the outcome inappropriate?",null,null,"N","Mortality is reported from a central database."]
[null,"4.2 Could measurement or ascertainment of the outcome have differed between intervention groups?",null,null,"N","Because of the nature of the outcome and due to it being reported centrally, measurement or ascertainment could not have differed between the two groups."]
[null,"4.3 Were outcome assessors aware of the intervention received by study participants?",null,null,"NI","The authors do not provisde any information with regards to blinding of the outcome assessors/assessment."]
[null,"4.4 If Y/PY/NI to 4.3: Could assessment of the outcome have been influenced by knowledge of intervention received?",null,null,"N","Knowledge of the assigned intervention is unlikely to influence all-cause mortality as this is an observer-reported outcome that does not involve judgement."]
[null,"4.5 If Y/PY/NI to 4.4: Is it likely that assessment of the outcome was influenced by knowledge of intervention received?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low","Mortality is reported from a central database.\r\nBecause of the nature of the outcome and due to it being reported centrally, measurement or ascertainment could not have differed between the two groups.\r\nThe authors do not provisde any information with regards to blinding of the outcome assessors/assessment.\r\nKnowledge of the assigned intervention is unlikely to influence all-cause mortality as this is an observer-reported outcome that does not involve judgement.\r\n"]
["Bias in selection of the reported result","5.1 Were the data that produced this result analysed in accordance with a pre-specified analysis plan that was finalized before unblinded outcome data were available for analysis?",null,null,"PY","Although there is no published protocol for this study and the authors make no mention as to if there was a pre-specified analysis plan, all-cause mortality is centrally recorded and as such there can not be selection of this outcome."]
[null,"5.2 ... multiple eligible outcome measurements (e.g. scales, definitions, time points) within the outcome domain?",null,null,"N","All-cause mortality is centrally recorded and as such there can not be selection of this outcome."]
[null,"5.3 ... multiple eligible analyses of the data?",null,null,"PN","All-cause mortality is centrally recorded and as such there can not be selection of this outcome."]
[null,"Risk of bias judgement",null,null,"Low","Although there is no published protocol for this study and the authors make no mention as to if there was a pre-specified analysis plan, all-cause mortality is centrally recorded and as such there can not be selection of this outcome.\r\nAll-cause mortality is centrally recorded and as such there can not be selection of this outcome.\r\nAll-cause mortality is centrally recorded and as such there can not be selection of this outcome."]
["Overall bias","Risk of bias judgement",null,null,"High","\r\n\r\nThe authors reported that only participants who did not drop out and were not lost to follow-up were included in analysis.\r\n The authors state that they used available case analysis but this does not account for missing data.\r\nEventhough the outcome is mortality and it is centrally registered, because the trial only included participants who were not lost to follow up, this might have affected the number of recorded deaths by this trial. The authors do not provide enough information to allow us further assess whether or not the missingness depended on its true value\r\n\r\nMortality is reported from a central database.\r\nBecause of the nature of the outcome and due to it being reported centrally, measurement or ascertainment could not have differed between the two groups.\r\nThe authors do not provisde any information with regards to blinding of the outcome assessors/assessment.\r\nKnowledge of the assigned intervention is unlikely to influence all-cause mortality as this is an observer-reported outcome that does not involve judgement.\r\n\r\nAlthough there is no published protocol for this study and the authors make no mention as to if there was a pre-specified analysis plan, all-cause mortality is centrally recorded and as such there can not be selection of this outcome.\r\nAll-cause mortality is centrally recorded and as such there can not be selection of this outcome.\r\nAll-cause mortality is centrally recorded and as such there can not be selection of this outcome."]
[]
[]
["Unique ID","2_A","Study ID","Pressler 2018","Assessor","LA"]
["Ref or Label","European Journal of Preventive Cardiology","Aim","assignment to intervention (the 'intention-to-treat' effect)\n\n"]
["Experimental","Exercise","Comparator","No Exercise","Source"," Journal article(s)"]
["Outcome","All-cause Mortality","Results","RR = 0.43 (95% CI 0.10, 1.85) (results from fig 1 in article)","Weight",90.1]
["Domain","Signalling question",null,null,"Response","Comments"]
["Bias arising from the randomization process","1.1 Was the allocation sequence random?",null,null,"Y","The authors state that “patients were randomly allocated 1:1 according to a computer-generated allocation program code”.\r\n\r\nAlthough there was no mention of allocation sequence concealment, the fact that they used a computer-generated program code would prevent the enrolling investigator or the participant from having any knowledge of the forthcoming allocation."]
[null,"1.2 Was the allocation sequence concealed until participants were enrolled and assigned to interventions?",null,null,"PY"]
[null,"1.3 Did baseline differences between intervention groups suggest a problem with the randomization process?",null,null,"N","No differences for TG and UC with respect to age, proportion of females, The Society of Thoracic Surgeons mortality risk score, NYHA class, prexisting conditions, and medication were observed (see Table I). "]
[null,"Risk of bias judgement",null,null,"Low","The authors state that “patients were randomly allocated 1:1 according to a computer-generated allocation program code”.\r\n\r\nAlthough there was no mention of allocation sequence concealment, the fact that they used a computer-generated program code would prevent the enrolling investigator or the participant from having any knowledge of the forthcoming allocation.\r\nNo differences for TG and UC with respect to age, proportion of females, The Society of Thoracic Surgeons mortality risk score, NYHA class, prexisting conditions, and medication were observed (see Table I). "]
["Bias due to deviations from intended interventions","2.1.Were participants aware of their assigned intervention during the trial?",null,null,"Y","Given the nature of an exercise-based CR intervention, participants are aware of their intervention and it might therefore not be possible to blind them, their carers, or the people delivering this intervention."]
[null,"2.2.Were carers and people delivering the interventions aware of participants' assigned intervention during the trial?",null,null,"Y"]
[null,"2.3. If Y/PY/NI to 2.1 or 2.2: Were there deviations from the intended intervention that arose because of the experimental context?",null,null,"PN","Although the authors do not specifically state if there were any deviations from the intended intervention, the flow of participants through the study (Fig 1 of 2016 paper and fig 1 of 2018 paper) shows that no participant changed groups during the study and all changes to the intervention were either consistent with the intervention (i.e. drop out due to unrelated causes) or consistent with what could occur outside of the trial context (i.e. drop out due to unwillingness to continue participation)."]
[null,"2.4 If Y/PY to 2.3: Were these deviations likely to have affected the outcome?",null,null,"NA"]
[null,"2.5. If Y/PY/NI to 2.4: Were these deviations from intended intervention balanced between groups?",null,null,"NA"]
[null,"2.6 Was an appropriate analysis used to estimate the effect of assignment to intervention?",null,null,"Y","Data were tested for their distribution and the primary end point and key secondary outcomes were normally distributed; thus it was decided to present data as mean (SD). Baseline differences between groups were analyzed using the Student t test for independent samples for continuous variables and the Fisher exact test for categorical variables. Between-group differences in changes of the primary and secondary end points were analyzed using the Student t test for independent samples. For relevant effect sizes (mean differences between study groups), 95% CIs are presented. Because of the low number of dropouts that were all unrelated to the intervention and the primary intention of the study to evaluate efficacy and safety of exercise, a per-protocol analysis was performed. To account for observed differences in baseline parameters between the study groups, linear regression models using the change in the measure of interest as dependent variable and the study group as well as the baseline value of the measure of interest as independent variable were fit to the data. "]
[null,"2.7 If N/PN/NI to 2.6: Was there potential for a substantial impact (on the result) of the failure to analyse participants in the group to which they were randomized?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low","Given the nature of an exercise-based CR intervention, participants are aware of their intervention and it might therefore not be possible to blind them, their carers, or the people delivering this intervention.\r\nAlthough the authors do not specifically state if there were any deviations from the intended intervention, the flow of participants through the study (Fig 1 of 2016 paper and fig 1 of 2018 paper) shows that no participant changed groups during the study and all changes to the intervention were either consistent with the intervention (i.e. drop out due to unrelated causes) or consistent with what could occur outside of the trial context (i.e. drop out due to unwillingness to continue participation).\r\n\r\n\r\nData were tested for their distribution and the primary end point and key secondary outcomes were normally distributed; thus it was decided to present data as mean (SD). Baseline differences between groups were analyzed using the Student t test for independent samples for continuous variables and the Fisher exact test for categorical variables. Between-group differences in changes of the primary and secondary end points were analyzed using the Student t test for independent samples. For relevant effect sizes (mean differences between study groups), 95% CIs are presented. Because of the low number of dropouts that were all unrelated to the intervention and the primary intention of the study to evaluate efficacy and safety of exercise, a per-protocol analysis was performed. To account for observed differences in baseline parameters between the study groups, linear regression models using the change in the measure of interest as dependent variable and the study group as well as the baseline value of the measure of interest as independent variable were fit to the data. \r\n"]
["Bias due to missing outcome data","3.1 Were data for this outcome available for all, or nearly all, participants randomized?",null,null,"Y","Outcome data was present for all participants."]
[null,"3.2 If N/PN/NI to 3.1: Is there evidence that result was not biased by missing outcome data?",null,null,"NA"]
[null,"3.3 If N/PN to 3.2: Could missingness in the outcome depend on its true value?",null,null,"NA"]
[null,"3.4 If Y/PY/NI to 3.3: Is it likely that missingness in the outcome depended on its true value?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low"]
["Bias in measurement of the outcome","4.1 Was the method of measuring the outcome inappropriate?",null,null,"N","Mortality is reported from a central database."]
[null,"4.2 Could measurement or ascertainment of the outcome have differed between intervention groups?",null,null,"N","Because of the nature of the outcome and due to it being reported centrally, measurement or ascertainment could not have differed between the two groups."]
[null,"4.3 Were outcome assessors aware of the intervention received by study participants?",null,null,"N","The authors state that 'All endpoints were performed and supervised by experienced staﬀ blinded to original group assignments'."]
[null,"4.4 If Y/PY/NI to 4.3: Could assessment of the outcome have been influenced by knowledge of intervention received?",null,null,"NA"]
[null,"4.5 If Y/PY/NI to 4.4: Is it likely that assessment of the outcome was influenced by knowledge of intervention received?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low","Mortality is reported from a central database.\r\nBecause of the nature of the outcome and due to it being reported centrally, measurement or ascertainment could not have differed between the two groups.\r\nThe authours state that 'All endpoints were performed and supervised by experienced staﬀ blinded to original group assignments'.\r\n\r\n"]
["Bias in selection of the reported result","5.1 Were the data that produced this result analysed in accordance with a pre-specified analysis plan that was finalized before unblinded outcome data were available for analysis?",null,null,"Y","The trial was registered on clinicaltrials.gov before start of the study (NCT01935297) with researchers’ pre-specified intentions available in sufficient detail. All-cause mortality is however centrally recorded and as such there can not be selection of this outcome."]
[null,"5.2 ... multiple eligible outcome measurements (e.g. scales, definitions, time points) within the outcome domain?",null,null,"N","The authors provided results for all timepoints at which this outcome was assessed with all extra analysis intended as exploratory analysis to provide additional information on the group-specific impact of the intervention."]
[null,"5.3 ... multiple eligible analyses of the data?",null,null,"N","The authors reported all results "]
[null,"Risk of bias judgement",null,null,"Low","The trial was registered on clinicaltrials.gov before start of the study (NCT01935297) with researchers’ pre-specified intentions available in sufficient detail. All-cause mortality is however centrally recorded and as such there can not be selection of this outcome.\r\nThe authors provided results for all timepoints at which this outcome was assessed with all extra analysis intended as exploratory analysis to provide additional information on the group-specific impact of the intervention.\r\nThe authors reported all results "]
["Overall bias","Risk of bias judgement",null,null,"Low","The authors state that “patients were randomly allocated 1:1 according to a computer-generated allocation program code”.\r\n\r\nAlthough there was no mention of allocation sequence concealment, the fact that they used a computer-generated program code would prevent the enrolling investigator or the participant from having any knowledge of the forthcoming allocation.\r\nNo differences for TG and UC with respect to age, proportion of females, The Society of Thoracic Surgeons mortality risk score, NYHA class, prexisting conditions, and medication were observed (see Table I). \r\nGiven the nature of an exercise-based CR intervention, participants are aware of their intervention and it might therefore not be possible to blind them, their carers, or the people delivering this intervention.\r\nAlthough the authors do not specifically state if there were any deviations from the intended intervention, the flow of participants through the study (Fig 1 of 2016 paper and fig 1 of 2018 paper) shows that no participant changed groups during the study and all changes to the intervention were either consistent with the intervention (i.e. drop out due to unrelated causes) or consistent with what could occur outside of the trial context (i.e. drop out due to unwillingness to continue participation).\r\n\r\n\r\nData were tested for their distribution and the primary end point and key secondary outcomes were normally distributed; thus it was decided to present data as mean (SD). Baseline differences between groups were analyzed using the Student t test for independent samples for continuous variables and the Fisher exact test for categorical variables. Between-group differences in changes of the primary and secondary end points were analyzed using the Student t test for independent samples. For relevant effect sizes (mean differences between study groups), 95% CIs are presented. Because of the low number of dropouts that were all unrelated to the intervention and the primary intention of the study to evaluate efficacy and safety of exercise, a per-protocol analysis was performed. To account for observed differences in baseline parameters between the study groups, linear regression models using the change in the measure of interest as dependent variable and the study group as well as the baseline value of the measure of interest as independent variable were fit to the data. \r\n\r\n\r\nMortality is reported from a central database.\r\nBecause of the nature of the outcome and due to it being reported centrally, measurement or ascertainment could not have differed between the two groups.\r\nThe authours state that 'All endpoints were performed and supervised by experienced staﬀ blinded to original group assignments'.\r\n\r\n\r\nThe trial was registered on clinicaltrials.gov before start of the study (NCT01935297) with researchers’ pre-specified intentions available in sufficient detail. All-cause mortality is however centrally recorded and as such there can not be selection of this outcome.\r\nThe authors provided results for all timepoints at which this outcome was assessed with all extra analysis intended as exploratory analysis to provide additional information on the group-specific impact of the intervention.\r\nThe authors reported all results "]
[]
[]
["Unique ID","3_A","Study ID","Sibilitz 2016","Assessor","LA"]
["Ref or Label","Heart 2016; 102: 1995-2003","Aim","assignment to intervention (the 'intention-to-treat' effect)\n\n"]
["Experimental","Exercise","Comparator","No Exercise","Source"," Journal article(s); Trial protocol"]
["Outcome","All-cause Hospitalisation","Results","RR = 2.72 (95% CI 0.11, 65.56)","Weight",100]
["Domain","Signalling question",null,null,"Response","Comments"]
["Bias arising from the randomization process","1.1 Was the allocation sequence random?",null,null,"Y","The authors state that “Participants were allocated 1:1 to intervention or control using computer-generated allocation sequence with varying block sizes of 8, 6 and 4, concealed to the investigators by central telephone correspondence with the Copenhagen Trial Unit.”"]
[null,"1.2 Was the allocation sequence concealed until participants were enrolled and assigned to interventions?",null,null,"Y"]
[null,"1.3 Did baseline differences between intervention groups suggest a problem with the randomization process?",null,null,"N","“There was no evidence of baseline imbalances.” Table 1 shows good balance in patient characteristics between groups"]
[null,"Risk of bias judgement",null,null,"Low","The authors state that “Participants were allocated 1:1 to intervention or control using computer-generated allocation sequence with varying block sizes of 8, 6 and 4, concealed to the investigators by central telephone correspondence with the Copenhagen Trial Unit.”\r\n“There was no evidence of baseline imbalances.” Table 1 shows good balance in patient characteristics between groups"]
["Bias due to deviations from intended interventions","2.1.Were participants aware of their assigned intervention during the trial?",null,null,"Y","Given the nature of an exercise-based CR intervention, participants are aware of their intervention and it might therefore not be possible to blind them, their carers, or the people delivering this intervention."]
[null,"2.2.Were carers and people delivering the interventions aware of participants' assigned intervention during the trial?",null,null,"Y"]
[null,"2.3. If Y/PY/NI to 2.1 or 2.2: Were there deviations from the intended intervention that arose because of the experimental context?",null,null,"PN","Although te authors do not expressesly mention if there were any deviations from the intended intervention, their CONSORT flow diagram of patients (fig 1 in article) shows that all participants were analysed in their initial intervention group."]
[null,"2.4 If Y/PY to 2.3: Were these deviations likely to have affected the outcome?",null,null,"NA"]
[null,"2.5. If Y/PY/NI to 2.4: Were these deviations from intended intervention balanced between groups?",null,null,"NA"]
[null,"2.6 Was an appropriate analysis used to estimate the effect of assignment to intervention?",null,null,"Y","The analysis was based on intention to treat using a mixed model with repeated measures (MMRM) and adjusted for the stratification variable of LVEF, ensuring that missing data will not create bias as long as the values are missing at random.25 The MMRM was used for continuous outcomes (both primary and secondary outcomes). This model assumes normally (Gaussian) distributed residuals. However, the residuals were not normally distributed for the primary outcome, and therefore transformed. We used log-transformation, and when log-transformation did not result in normally distributed residuals, we used Box–Cox transformation. In the MMRM we assumed correlation within the individual patient, but no correlation between patients. The fixed effects for the primary outcome were randomisation group, time, interaction between random and time and LVEF."]
[null,"2.7 If N/PN/NI to 2.6: Was there potential for a substantial impact (on the result) of the failure to analyse participants in the group to which they were randomized?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low","Given the nature of an exercise-based CR intervention, participants are aware of their intervention and it might therefore not be possible to blind them, their carers, or the people delivering this intervention.\r\nAlthough te authors do not expressesly mention if there were any deviations from the intended intervention, their CONSORT flow diagram of patients (fig 1 in article) shows that all participants were analysed in their initial intervention group.\r\n\r\n\r\nThe analysis was based on intention to treat using a mixed model with repeated measures (MMRM) and adjusted for the stratification variable of LVEF, ensuring that missing data will not create bias as long as the values are missing at random.25 The MMRM was used for continuous outcomes (both primary and secondary outcomes). This model assumes normally (Gaussian) distributed residuals. However, the residuals were not normally distributed for the primary outcome, and therefore transformed. We used log-transformation, and when log-transformation did not result in normally distributed residuals, we used Box–Cox transformation. In the MMRM we assumed correlation within the individual patient, but no correlation between patients. The fixed effects for the primary outcome were randomisation group, time, interaction between random and time and LVEF.\r\n"]
["Bias due to missing outcome data","3.1 Were data for this outcome available for all, or nearly all, participants randomized?",null,null,"N","Considering the fact that the appropriate study population for an analysis of the intention to treat effect is all randomized participants, in this Trial, less than 95% of the participants in either the exercise group or the control group provided data for this outcome. The authors do state that the drop outs were due to complications after surgery and withdrawal of consent with 9 people dropping out of the study before completing 1 month of exercise training or usual care."]
[null,"3.2 If N/PN/NI to 3.1: Is there evidence that result was not biased by missing outcome data?",null,null,"N","There is no evidence to prove that the results was not biased by missing outcome data as the only sensitivity analysis carried out was for VO2.  "]
[null,"3.3 If N/PN to 3.2: Could missingness in the outcome depend on its true value?",null,null,"PY","There is no considerable difference in the proportions of missing outcome data between the two groups.\r\nThe authors do state that the drop outs were due to complications after surgery and withdrawal of consent, but no mention was made to suggest that the intervention played a part in this withdrawal.\r\nReported reasons for missing outcome data are similar between both groups.\r\nThe circumstances of the trial do not make it likely that missingness in the outcome depends on its true value as more participants dropped out of the control group than from the exercise group."]
[null,"3.4 If Y/PY/NI to 3.3: Is it likely that missingness in the outcome depended on its true value?",null,null,"N"]
[null,"Risk of bias judgement",null,null,"Some concerns","Considering the fact that the appropriate study population for an analysis of the intention to treat effect is all randomized participants, in this Trial, less than 95% of the participants in either the exercise group or the control group provided data for this outcome. The authors do state that the drop outs were due to complications after surgery and withdrawal of consent with 9 people dropping out of the study before completing 1 month of exercise training or usual care.\r\nThere is no evidence to prove that the results was not biased by missing outcome data as the only sensitivity analysis carried out was for VO2.  \r\nThere is no considerable difference in the proportions of missing outcome data between the two groups.\r\nThe authors do state that the drop outs were due to complications after surgery and withdrawal of consent, but no mention was made to suggest that the intervention played a part in this withdrawal.\r\nReported reasons for missing outcome data are similar between both groups.\r\nThe circumstances of the trial do not make it likely that missingness in the outcome depends on its true value as more participants dropped out of the control group than from the exercise group.\r\n"]
["Bias in measurement of the outcome","4.1 Was the method of measuring the outcome inappropriate?",null,null,"N","Hospitalisation like mortality is centrally reported."]
[null,"4.2 Could measurement or ascertainment of the outcome have differed between intervention groups?",null,null,"N","Because of its central reporting, measurement or ascertainment could not have differed between the two groups."]
[null,"4.3 Were outcome assessors aware of the intervention received by study participants?",null,null,"N","“The trial applied central, stratified randomisation securing against selection bias, and blinded outcome assessment and blinded statistical analyses, reducing detection and interpretation bias”"]
[null,"4.4 If Y/PY/NI to 4.3: Could assessment of the outcome have been influenced by knowledge of intervention received?",null,null,"NA"]
[null,"4.5 If Y/PY/NI to 4.4: Is it likely that assessment of the outcome was influenced by knowledge of intervention received?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low","Hospitalisation like mortality is centrally reported.\r\nBecause of its central reporting, measurement or ascertainment could not have differed between the two groups.\r\n“The trial applied central, stratified randomisation securing against selection bias, and blinded outcome assessment and blinded statistical analyses, reducing detection and interpretation bias”\r\n\r\n"]
["Bias in selection of the reported result","5.1 Were the data that produced this result analysed in accordance with a pre-specified analysis plan that was finalized before unblinded outcome data were available for analysis?",null,null,"Y","Trial registered on clinicaltrials.gov before start of the study  (NCT01558765) with researchers’ pre-specified intentions available in sufficient detail. The central recording of all-cause hospitalisations however makes it an outcome which can not be selected against."]
[null,"5.2 ... multiple eligible outcome measurements (e.g. scales, definitions, time points) within the outcome domain?",null,null,"N","The authors provided results for all timepoints at which this outcome was assessed (6months) within the scope of this article."]
[null,"5.3 ... multiple eligible analyses of the data?",null,null,"N","There is no evidence of multiple eligible analyses for this outcome."]
[null,"Risk of bias judgement",null,null,"Low","Trial registered on clinicaltrials.gov before start of the study  (NCT01558765) with researchers’ pre-specified intentions available in sufficient detail. The central recording of all-cause hospitalisations however makes it an outcome which can not be selected against.\r\nThe authors provided results for all timepoints at which this outcome was assessed (6months) within the scope of this article.\r\nThere is no evidence of multiple eligible analyses for this outcome."]
["Overall bias","Risk of bias judgement",null,null,"Some concerns","The authors state that “Participants were allocated 1:1 to intervention or control using computer-generated allocation sequence with varying block sizes of 8, 6 and 4, concealed to the investigators by central telephone correspondence with the Copenhagen Trial Unit.”\r\n“There was no evidence of baseline imbalances.” Table 1 shows good balance in patient characteristics between groups\r\nGiven the nature of an exercise-based CR intervention, participants are aware of their intervention and it might therefore not be possible to blind them, their carers, or the people delivering this intervention.\r\nAlthough te authors do not expressesly mention if there were any deviations from the intended intervention, their CONSORT flow diagram of patients (fig 1 in article) shows that all participants were analysed in their initial intervention group.\r\n\r\n\r\nThe analysis was based on intention to treat using a mixed model with repeated measures (MMRM) and adjusted for the stratification variable of LVEF, ensuring that missing data will not create bias as long as the values are missing at random.25 The MMRM was used for continuous outcomes (both primary and secondary outcomes). This model assumes normally (Gaussian) distributed residuals. However, the residuals were not normally distributed for the primary outcome, and therefore transformed. We used log-transformation, and when log-transformation did not result in normally distributed residuals, we used Box–Cox transformation. In the MMRM we assumed correlation within the individual patient, but no correlation between patients. The fixed effects for the primary outcome were randomisation group, time, interaction between random and time and LVEF.\r\n\r\nLess than 95% of the participants in either the exercise group or the control group provided data for this outcome. The authors do state that the drop outs were due to complications after surgery and withdrawal of consent with 9 people dropping out of the study before completing 1 month of exercise training or usual care.\r\nThere is no evidence to prove that the results was not biased by missing outcome data as the only sensitivity analysis carried out was for VO2.  \r\nThere is no considerable difference in the proportions of missing outcome data between the two groups.\r\nThe authors do state that the drop outs were due to complications after surgery and withdrawal of consent, but no mention was made to suggest that the intervention played a part in this withdrawal.\r\nReported reasons for missing outcome data are similar between both groups.\r\nThe circumstances of the trial do not make it likely that missingness in the outcome depends on its true value as more participants dropped out of the control group than from the exercise group.\r\n\r\nHospitalisation like mortality is centrally reported.\r\nBecause of its central reporting, measurement or ascertainment could not have differed between the two groups.\r\n“The trial applied central, stratified randomisation securing against selection bias, and blinded outcome assessment and blinded statistical analyses, reducing detection and interpretation bias”\r\n\r\n\r\nTrial registered on clinicaltrials.gov before start of the study  (NCT01558765) with researchers’ pre-specified intentions available in sufficient detail. The central recording of all-cause hospitalisations however makes it an outcome which can not be selected against.\r\nThe authors provided results for all timepoints at which this outcome was assessed (6months) within the scope of this article.\r\nThere is no evidence of multiple eligible analyses for this outcome."]
[]
[]
["Unique ID","2_B","Study ID","Pressler 2016","Assessor","LA"]
["Ref or Label","American Heart Journal vol 182; pp. 44-53","Aim","assignment to intervention (the 'intention-to-treat' effect)\n\n"]
["Experimental","Exercise","Comparator","No Exercise","Source"," Journal article(s)"]
["Outcome","HRQoL (MC at end of intervention)","Results","MD = 3 (95% CI -3.16, 9.16)","Weight",21.8]
["Domain","Signalling question",null,null,"Response","Comments"]
["Bias arising from the randomization process","1.1 Was the allocation sequence random?",null,null,"Y","The authors state that “patients were randomly allocated 1:1 according to a computer-generated allocation program code”.\r\nAlthough there was no mention of allocation sequence concealment, the fact that they used a computer-generated program code would prevent the enrolling investigator or the participant from having any knowledge of the forthcoming allocation."]
[null,"1.2 Was the allocation sequence concealed until participants were enrolled and assigned to interventions?",null,null,"PY"]
[null,"1.3 Did baseline differences between intervention groups suggest a problem with the randomization process?",null,null,"N","No differences for TG and UC with respect to age, proportion of females, The Society of Thoracic Surgeons mortality risk score, NYHA class, prexisting conditions, and medication were observed (see Table I)."]
[null,"Risk of bias judgement",null,null,"Low","The authors state that “patients were randomly allocated 1:1 according to a computer-generated allocation program code”.\r\nAlthough there was no mention of allocation sequence concealment, the fact that they used a computer-generated program code would prevent the enrolling investigator or the participant from having any knowledge of the forthcoming allocation.\r\nNo differences for TG and UC with respect to age, proportion of females, The Society of Thoracic Surgeons mortality risk score, NYHA class, prexisting conditions, and medication were observed (see Table I)."]
["Bias due to deviations from intended interventions","2.1.Were participants aware of their assigned intervention during the trial?",null,null,"Y","Given the nature of an exercise-based CR intervention, participants are aware of their intervention and it might therefore not be possible to blind them, their carers, or the people delivering this intervention."]
[null,"2.2.Were carers and people delivering the interventions aware of participants' assigned intervention during the trial?",null,null,"Y"]
[null,"2.3. If Y/PY/NI to 2.1 or 2.2: Were there deviations from the intended intervention that arose because of the experimental context?",null,null,"PN","Although the authors do not specifically state if there were any deviations from the intended intervention, the flow of participants through the study (Fig 1 of 2016 paper and fig 1 of 2018 paper) shows that no participant changed groups during the study and all changes to the intervention were either consistent with the intervention (i.e. drop out due to unrelated causes) or consistent with what could occur outside of the trial context (i.e. drop out due to unwillingness to continue participation)."]
[null,"2.4 If Y/PY to 2.3: Were these deviations likely to have affected the outcome?",null,null,"NA"]
[null,"2.5. If Y/PY/NI to 2.4: Were these deviations from intended intervention balanced between groups?",null,null,"NA"]
[null,"2.6 Was an appropriate analysis used to estimate the effect of assignment to intervention?",null,null,"Y","Data were tested for their distribution and the primary end point and key secondary outcomes were normally distributed; thus it was decided to present data as mean (SD). Baseline differences between groups were analyzed using the Student t test for independent samples for continuous variables and the Fisher exact test for categorical variables. Between-group differences in changes of the primary and secondary end points were analyzed using the Student t test for independent samples. For relevant effect sizes (mean differences between study groups), 95% CIs are presented. Because of the low number of dropouts that were all unrelated to the intervention and the primary intention of the study to evaluate efficacy and safety of exercise, a per-protocol analysis was performed. To account for observed differences in baseline parameters between the study groups, linear regression models using the change in the measure of interest as dependent variable and the study group as well as the baseline value of the measure of interest as independent variable were fit to the data. "]
[null,"2.7 If N/PN/NI to 2.6: Was there potential for a substantial impact (on the result) of the failure to analyse participants in the group to which they were randomized?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low","Given the nature of an exercise-based CR intervention, participants are aware of their intervention and it might therefore not be possible to blind them, their carers, or the people delivering this intervention.\r\nAlthough the authors do not specifically state if there were any deviations from the intended intervention, the flow of participants through the study (Fig 1 of 2016 paper and fig 1 of 2018 paper) shows that no participant changed groups during the study and all changes to the intervention were either consistent with the intervention (i.e. drop out due to unrelated causes) or consistent with what could occur outside of the trial context (i.e. drop out due to unwillingness to continue participation).\r\n\r\n\r\nData were tested for their distribution and the primary end point and key secondary outcomes were normally distributed; thus it was decided to present data as mean (SD). Baseline differences between groups were analyzed using the Student t test for independent samples for continuous variables and the Fisher exact test for categorical variables. Between-group differences in changes of the primary and secondary end points were analyzed using the Student t test for independent samples. For relevant effect sizes (mean differences between study groups), 95% CIs are presented. Because of the low number of dropouts that were all unrelated to the intervention and the primary intention of the study to evaluate efficacy and safety of exercise, a per-protocol analysis was performed. To account for observed differences in baseline parameters between the study groups, linear regression models using the change in the measure of interest as dependent variable and the study group as well as the baseline value of the measure of interest as independent variable were fit to the data. \r\n"]
["Bias due to missing outcome data","3.1 Were data for this outcome available for all, or nearly all, participants randomized?",null,null,"N","Considering the fact that the appropriate study population for an analysis of the intention to treat effect is all randomized participants, in this Trial,  less than 95% of the participants in either the exercise group or the control group provided data for this outcome, as there were 3 overall drop outs (2/15 in exercise group and 1/15 in control group). "]
[null,"3.2 If N/PN/NI to 3.1: Is there evidence that result was not biased by missing outcome data?",null,null,"Y","Because of the low number of dropouts that were all unrelated to the intervention and the primary intention of the study to evaluate efficacy and safety of exercise, a per-protocol analysis was performed."]
[null,"3.3 If N/PN to 3.2: Could missingness in the outcome depend on its true value?",null,null,"NA"]
[null,"3.4 If Y/PY/NI to 3.3: Is it likely that missingness in the outcome depended on its true value?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low","Considering the fact that the appropriate study population for an analysis of the intention to treat effect is all randomized participants, in this Trial,  less than 95% of the participants in either the exercise group or the control group provided data for this outcome, as there were 3 overall drop outs (2/15 in exercise group and 1/15 in control group). \r\nBecause of the low number of dropouts that were all unrelated to the intervention and the primary intention of the study to evaluate efficacy and safety of exercise, a per-protocol analysis was performed.\r\n\r\n"]
["Bias in measurement of the outcome","4.1 Was the method of measuring the outcome inappropriate?",null,null,"N","HRQoL measured using SF36 and KCCQ both of which are validated questionnaires"]
[null,"4.2 Could measurement or ascertainment of the outcome have differed between intervention groups?",null,null,"N","Measurements were made in the same way for both intervention and control "]
[null,"4.3 Were outcome assessors aware of the intervention received by study participants?",null,null,"Y","The person reporting this outcome is the participant and they are aware of the intervention received. Collation and analysis of the results were most likely carried out by study personnel who were blinded to the intervention recived by the study participant."]
[null,"4.4 If Y/PY/NI to 4.3: Could assessment of the outcome have been influenced by knowledge of intervention received?",null,null,"Y","The assessment by the participants could have been affected by knowledge of the intervention as it is subjective. Exercise is generally believed to be a beneficial intervention in this patient group and it is possible that participants might have considered their HRQoL would be better if they had the intervention."]
[null,"4.5 If Y/PY/NI to 4.4: Is it likely that assessment of the outcome was influenced by knowledge of intervention received?",null,null,"PY"]
[null,"Risk of bias judgement",null,null,"High","HRQoL measured using SF36 and KCCQ both of which are validated questionnaires\r\nMeasurements were made in the same way for both intervention and control \r\nThe person reporting this outcome is the participant and they are aware of the intervention received. Collation and analysis of the results were most likely carried out by study personnel who were blinded to the intervention recived by the study participant.\r\nThe assessment by the participants could have been affected by knowledge of the intervention as it is subjective. Exercise is generally believed to be a beneficial intervention in this patient group and it is possible that participants might have considered their HRQoL would be better if they had the intervention.\r\n"]
["Bias in selection of the reported result","5.1 Were the data that produced this result analysed in accordance with a pre-specified analysis plan that was finalized before unblinded outcome data were available for analysis?",null,null,"Y","The trial was registered on clinicaltrials.gov before start of the study (NCT01935297) with researchers’ pre-specified intentions available in sufficient detail. There is no reason to believe that the data which produced this result was not analysed in accordance with a pre-specified analysis plan."]
[null,"5.2 ... multiple eligible outcome measurements (e.g. scales, definitions, time points) within the outcome domain?",null,null,"N","The authors provided results for all timepoints at which this outcome was assessed with all extra analysis intended as exploratory analysis to provide additional information on the group-specific impact of the intervention."]
[null,"5.3 ... multiple eligible analyses of the data?",null,null,"N","The authors reported all results. There is therefore no reason to believe that this result might have been selected from multiple eligible analyses of the data."]
[null,"Risk of bias judgement",null,null,"Low","The trial was registered on clinicaltrials.gov before start of the study (NCT01935297) with researchers’ pre-specified intentions available in sufficient detail. There is no reason to believe that the data which produced this result was not analysed in accordance with a pre-specified analysis plan.\r\nThe authors provided results for all timepoints at which this outcome was assessed with all extra analysis intended as exploratory analysis to provide additional information on the group-specific impact of the intervention.\r\nThe authors reported all results. There is therefore no reason to believe that this result might have been selected from multiple eligible analyses of the data."]
["Overall bias","Risk of bias judgement",null,null,"High","The authors state that “patients were randomly allocated 1:1 according to a computer-generated allocation program code”.\r\nAlthough there was no mention of allocation sequence concealment, the fact that they used a computer-generated program code would prevent the enrolling investigator or the participant from having any knowledge of the forthcoming allocation.\r\nNo differences for TG and UC with respect to age, proportion of females, The Society of Thoracic Surgeons mortality risk score, NYHA class, prexisting conditions, and medication were observed (see Table I).\r\nGiven the nature of an exercise-based CR intervention, participants are aware of their intervention and it might therefore not be possible to blind them, their carers, or the people delivering this intervention.\r\nAlthough the authors do not specifically state if there were any deviations from the intended intervention, the flow of participants through the study (Fig 1 of 2016 paper and fig 1 of 2018 paper) shows that no participant changed groups during the study and all changes to the intervention were either consistent with the intervention (i.e. drop out due to unrelated causes) or consistent with what could occur outside of the trial context (i.e. drop out due to unwillingness to continue participation).\r\n\r\n\r\nData were tested for their distribution and the primary end point and key secondary outcomes were normally distributed; thus it was decided to present data as mean (SD). Baseline differences between groups were analyzed using the Student t test for independent samples for continuous variables and the Fisher exact test for categorical variables. Between-group differences in changes of the primary and secondary end points were analyzed using the Student t test for independent samples. For relevant effect sizes (mean differences between study groups), 95% CIs are presented. Because of the low number of dropouts that were all unrelated to the intervention and the primary intention of the study to evaluate efficacy and safety of exercise, a per-protocol analysis was performed. To account for observed differences in baseline parameters between the study groups, linear regression models using the change in the measure of interest as dependent variable and the study group as well as the baseline value of the measure of interest as independent variable were fit to the data. \r\n\r\nConsidering the fact that the appropriate study population for an analysis of the intention to treat effect is all randomized participants, in this Trial,  less than 95% of the participants in either the exercise group or the control group provided data for this outcome, as there were 3 overall drop outs. \r\nBecause of the low number of dropouts that were all unrelated to the intervention and the primary intention of the study to evaluate efficacy and safety of exercise, a per-protocol analysis was performed.\r\n\r\n\r\nHRQoL measured using SF36 and KCCQ both of which are validated questionnaires\r\nMeasurements were made in the same way for both intervention and control \r\nThe person reporting this outcome is the participant and they are aware of the intervention received. Collation and analysis of the results were most likely carried out by study personnel who were blinded to the intervention recived by the study participant.\r\nThe assessment by the participants could have been affected by knowledge of the intervention as it is subjective. Exercise is generally believed to be a beneficial intervention in this patient group and it is possible that participants might have considered their HRQoL would be better if they had the intervention.\r\n\r\nThe trial was registered on clinicaltrials.gov before start of the study (NCT01935297) with researchers’ pre-specified intentions available in sufficient detail. There is no reason to believe that the data which produced this result was not analysed in accordance with a pre-specified analysis plan. \r\nThe authors provided results for all timepoints at which this outcome was assessed with all extra analysis intended as exploratory analysis to provide additional information on the group-specific impact of the intervention.\r\nThe authors reported all results. There is therefore no reason to believe that this result might have been selected from multiple eligible analyses of the data."]
[]
[]
["Unique ID","3_B","Study ID","Sibilitz 2016","Assessor","LA"]
["Ref or Label","Heart 2016; 102: 1995-2003","Aim","assignment to intervention (the 'intention-to-treat' effect)\n\n"]
["Experimental","Exercise","Comparator","No Exercise","Source"," Journal article(s)"]
["Outcome","HRQoL (MC at end of intervention)","Results","MD = 0.80 (95% CI -2.46, 4.06)","Weight",78.2]
["Domain","Signalling question",null,null,"Response","Comments"]
["Bias arising from the randomization process","1.1 Was the allocation sequence random?",null,null,"Y","The authors state that “Participants were allocated 1:1 to intervention or control using computer-generated allocation sequence with varying block sizes of 8, 6 and 4, concealed to the investigators by central telephone correspondence with the Copenhagen Trial Unit.”"]
[null,"1.2 Was the allocation sequence concealed until participants were enrolled and assigned to interventions?",null,null,"Y"]
[null,"1.3 Did baseline differences between intervention groups suggest a problem with the randomization process?",null,null,"N","“There was no evidence of baseline imbalances.” Table 1 shows good balance in patient characteristics between groups"]
[null,"Risk of bias judgement",null,null,"Low","The authors state that “Participants were allocated 1:1 to intervention or control using computer-generated allocation sequence with varying block sizes of 8, 6 and 4, concealed to the investigators by central telephone correspondence with the Copenhagen Trial Unit.”\r\n“There was no evidence of baseline imbalances.” Table 1 shows good balance in patient characteristics between groups"]
["Bias due to deviations from intended interventions","2.1.Were participants aware of their assigned intervention during the trial?",null,null,"Y","Given the nature of an exercise-based CR intervention, participants are aware of their intervention and it might therefore not be possible to blind them, their carers, or the people delivering this intervention."]
[null,"2.2.Were carers and people delivering the interventions aware of participants' assigned intervention during the trial?",null,null,"Y"]
[null,"2.3. If Y/PY/NI to 2.1 or 2.2: Were there deviations from the intended intervention that arose because of the experimental context?",null,null,"PN","Although te authors do not expressesly mention if there were any deviations from the intended intervention, their CONSORT flow diagram of patients (fig 1 in article) shows that all participants were analysed in their initial intervention group."]
[null,"2.4 If Y/PY to 2.3: Were these deviations likely to have affected the outcome?",null,null,"NA"]
[null,"2.5. If Y/PY/NI to 2.4: Were these deviations from intended intervention balanced between groups?",null,null,"NA"]
[null,"2.6 Was an appropriate analysis used to estimate the effect of assignment to intervention?",null,null,"Y","The analysis was based on intention to treat using a mixed model with repeated measures (MMRM) and adjusted for the stratification variable of LVEF, ensuring that missing data will not create bias as long as the values are missing at random.25 The MMRM was used for continuous outcomes (both primary and secondary outcomes). This model assumes normally (Gaussian) distributed residuals. However, the residuals were not normally distributed for the primary outcome, and therefore transformed. We used log-transformation, and when log-transformation did not result in normally distributed residuals, we used Box–Cox transformation. In the MMRM we assumed correlation within the individual patient, but no correlation between patients. The fixed effects for the primary outcome were randomisation group, time, interaction between random and time and LVEF."]
[null,"2.7 If N/PN/NI to 2.6: Was there potential for a substantial impact (on the result) of the failure to analyse participants in the group to which they were randomized?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low","Given the nature of an exercise-based CR intervention, participants are aware of their intervention and it might therefore not be possible to blind them, their carers, or the people delivering this intervention.\r\nAlthough te authors do not expressesly mention if there were any deviations from the intended intervention, their CONSORT flow diagram of patients (fig 1 in article) shows that all participants were analysed in their initial intervention group.\r\n\r\n\r\nThe analysis was based on intention to treat using a mixed model with repeated measures (MMRM) and adjusted for the stratification variable of LVEF, ensuring that missing data will not create bias as long as the values are missing at random.25 The MMRM was used for continuous outcomes (both primary and secondary outcomes). This model assumes normally (Gaussian) distributed residuals. However, the residuals were not normally distributed for the primary outcome, and therefore transformed. We used log-transformation, and when log-transformation did not result in normally distributed residuals, we used Box–Cox transformation. In the MMRM we assumed correlation within the individual patient, but no correlation between patients. The fixed effects for the primary outcome were randomisation group, time, interaction between random and time and LVEF.\r\n"]
["Bias due to missing outcome data","3.1 Were data for this outcome available for all, or nearly all, participants randomized?",null,null,"N","Considering the fact that the appropriate study population for an analysis of the intention to treat effect is all randomized participants, in this Trial,  less than 95% of the participants in either the exercise group or the control group provided data for this outcome. The authors do state that the drop outs were due to complications after surgery and withdrawal of consent with 9 people dropping out of the study before completing 1 month of exercise training or usual care."]
[null,"3.2 If N/PN/NI to 3.1: Is there evidence that result was not biased by missing outcome data?",null,null,"N","There is no evidence to prove that the results was not biased by missing outcome data"]
[null,"3.3 If N/PN to 3.2: Could missingness in the outcome depend on its true value?",null,null,"PY","There is no considerable difference in the proportions of missing outcome data between the two groups.\r\nThe authors do state that the drop outs were due to complications after surgery and withdrawal of consent, but no mention was made to suggest that the intervention played a part in this withdrawal.\r\nReported reasons for missing outcome data are similar between both groups.\r\nThe circumstances of the trial do not make it likely that missingness in the outcome depends on its true value as more participants dropped out of the control group than from the exercise group."]
[null,"3.4 If Y/PY/NI to 3.3: Is it likely that missingness in the outcome depended on its true value?",null,null,"N"]
[null,"Risk of bias judgement",null,null,"Some concerns","Considering the fact that the appropriate study population for an analysis of the intention to treat effect is all randomized participants, in this Trial,  less than 95% of the participants in either the exercise group or the control group provided data for this outcome. The authors do state that the drop outs were due to complications after surgery and withdrawal of consent with 9 people dropping out of the study before completing 1 month of exercise training or usual care.\r\nThere is no evidence to prove that the results was not biased by missing outcome data\r\nThere is no considerable difference in the proportions of missing outcome data between the two groups.\r\nThe authors do state that the drop outs were due to complications after surgery and withdrawal of consent, but no mention was made to suggest that the intervention played a part in this withdrawal.\r\nReported reasons for missing outcome data are similar between both groups.\r\nThe circumstances of the trial do not make it likely that missingness in the outcome depends on its true value as more participants dropped out of the control group than from the exercise group.\r\n"]
["Bias in measurement of the outcome","4.1 Was the method of measuring the outcome inappropriate?",null,null,"N","HRQoL measured using SF36, a validated questionnaire"]
[null,"4.2 Could measurement or ascertainment of the outcome have differed between intervention groups?",null,null,"N","Measurements were made in the same way for both intervention and control "]
[null,"4.3 Were outcome assessors aware of the intervention received by study participants?",null,null,"Y","The person reporting this outcome is the participant and they are aware of the intervention they received. Collation and analysis of the results were most likely arried out by study personnel who were blinded. \r\n“The trial applied central, stratified randomisation securing against selection bias, and blinded outcome assessment and blinded statistical analyses, reducing detection and interpretation bias”"]
[null,"4.4 If Y/PY/NI to 4.3: Could assessment of the outcome have been influenced by knowledge of intervention received?",null,null,"Y","The assessment by the participants could have been affected by knowledge of the intervention as it is subjective. Exercise is generally believed to be a beneficial intervention in this patient group and it is possible that participants might have considered their HRQoL would be better if they had the intervention."]
[null,"4.5 If Y/PY/NI to 4.4: Is it likely that assessment of the outcome was influenced by knowledge of intervention received?",null,null,"PY"]
[null,"Risk of bias judgement",null,null,"High","HRQoL measured using SF36, a validated questionnaire\r\nMeasurements were made in the same way for both intervention and control \r\nThe person reporting this outcome is the participant and they are aware of the intervention they received. Collation and analysis of the results were most likely arried out by study personnel who were blinded. \r\n“The trial applied central, stratified randomisation securing against selection bias, and blinded outcome assessment and blinded statistical analyses, reducing detection and interpretation bias”\r\nThe assessment by the participants could have been affected by knowledge of the intervention as it is subjective. Exercise is generally believed to be a beneficial intervention in this patient group and it is possible that participants might have considered their HRQoL would be better if they had the intervention.\r\n"]
["Bias in selection of the reported result","5.1 Were the data that produced this result analysed in accordance with a pre-specified analysis plan that was finalized before unblinded outcome data were available for analysis?",null,null,"Y","Trial registered on clinicaltrials.gov before start of the study  (NCT01558765) with researchers’ pre-specified intentions available in sufficient detail. There is therefore no reason to believe that the reults would not have been analysed in accordance with a pre-specified analysis plan."]
[null,"5.2 ... multiple eligible outcome measurements (e.g. scales, definitions, time points) within the outcome domain?",null,null,"N","The authors provided results for all timepoints at which this outcome was assessed within the scope of this article."]
[null,"5.3 ... multiple eligible analyses of the data?",null,null,"N","There is no evidence of multiple eligible analyses for this outcome."]
[null,"Risk of bias judgement",null,null,"Low","Trial registered on clinicaltrials.gov before start of the study  (NCT01558765) with researchers’ pre-specified intentions available in sufficient detail. There is therefore no reason to believe that the reults would not have been analysed in accordance with a pre-specified analysis plan.\r\nThe authors provided results for all timepoints at which this outcome was assessed within the scope of this article.\r\nThere is no evidence of multiple eligible analyses for this outcome."]
["Overall bias","Risk of bias judgement",null,null,"High","The authors state that “Participants were allocated 1:1 to intervention or control using computer-generated allocation sequence with varying block sizes of 8, 6 and 4, concealed to the investigators by central telephone correspondence with the Copenhagen Trial Unit.”\r\n“There was no evidence of baseline imbalances.” Table 1 shows good balance in patient characteristics between groups\r\nGiven the nature of an exercise-based CR intervention, participants are aware of their intervention and it might therefore not be possible to blind them, their carers, or the people delivering this intervention.\r\nAlthough te authors do not expressesly mention if there were any deviations from the intended intervention, their CONSORT flow diagram of patients (fig 1 in article) shows that all participants were analysed in their initial intervention group.\r\n\r\n\r\nThe analysis was based on intention to treat using a mixed model with repeated measures (MMRM) and adjusted for the stratification variable of LVEF, ensuring that missing data will not create bias as long as the values are missing at random.25 The MMRM was used for continuous outcomes (both primary and secondary outcomes). This model assumes normally (Gaussian) distributed residuals. However, the residuals were not normally distributed for the primary outcome, and therefore transformed. We used log-transformation, and when log-transformation did not result in normally distributed residuals, we used Box–Cox transformation. In the MMRM we assumed correlation within the individual patient, but no correlation between patients. The fixed effects for the primary outcome were randomisation group, time, interaction between random and time and LVEF.\r\n\r\nConsidering the fact that the appropriate study population for an analysis of the intention to treat effect is all randomized participants, in this Trial,  less than 95% of the participants in either the exercise group or the control group provided data for this outcome. The authors do state that the drop outs were due to complications after surgery and withdrawal of consent with 9 people dropping out of the study before completing 1 month of exercise training or usual care.\r\nThere is no evidence to prove that the results was not biased by missing outcome data\r\nThere is no considerable difference in the proportions of missing outcome data between the two groups.\r\nThe authors do state that the drop outs were due to complications after surgery and withdrawal of consent, but no mention was made to suggest that the intervention played a part in this withdrawal.\r\nReported reasons for missing outcome data are similar between both groups.\r\nThe circumstances of the trial do not make it likely that missingness in the outcome depends on its true value as more participants dropped out of the control group than from the exercise group.\r\n\r\nHRQoL measured using SF36, a validated questionnaire\r\nMeasurements were made in the same way for both intervention and control \r\nThe person reporting this outcome is the participant and they are aware of the intervention they received. Collation and analysis of the results were most likely arried out by study personnel who were blinded. \r\n“The trial applied central, stratified randomisation securing against selection bias, and blinded outcome assessment and blinded statistical analyses, reducing detection and interpretation bias”\r\nThe assessment by the participants could have been affected by knowledge of the intervention as it is subjective. Exercise is generally believed to be a beneficial intervention in this patient group and it is possible that participants might have considered their HRQoL would be better if they had the intervention.\r\n\r\nTrial registered on clinicaltrials.gov before start of the study  (NCT01558765) with researchers’ pre-specified intentions available in sufficient detail. There is therefore no reason to believe that the reults would not have been analysed in accordance with a pre-specified analysis plan.\r\nThe authors provided results for all timepoints at which this outcome was assessed within the scope of this article.\r\nThere is no evidence of multiple eligible analyses for this outcome."]
[]
[]
["Unique ID","2_C","Study ID","Pressler 2016","Assessor","LA"]
["Ref or Label","American Heart Journal vol 182; pp. 44-53","Aim","assignment to intervention (the 'intention-to-treat' effect)\n\n"]
["Experimental","Exercise","Comparator","No Exercise","Source"," Journal article(s)"]
["Outcome","HRQoL (PC at end of intervention)","Results","MD = 7.9 (95% CI 0.73, 15.07)","Weight",42.2]
["Domain","Signalling question",null,null,"Response","Comments"]
["Bias arising from the randomization process","1.1 Was the allocation sequence random?",null,null,"Y","The authors state that “patients were randomly allocated 1:1 according to a computer-generated allocation program code”.\r\n\r\nAlthough there was no mention of allocation sequence concealment, the fact that they used a computer-generated program code would prevent the enrolling investigator or the participant from having any knowledge of the forthcoming allocation."]
[null,"1.2 Was the allocation sequence concealed until participants were enrolled and assigned to interventions?",null,null,"PY"]
[null,"1.3 Did baseline differences between intervention groups suggest a problem with the randomization process?",null,null,"N","No differences for TG and UC with respect to age, proportion of females, The Society of Thoracic Surgeons mortality risk score, NYHA class, prexisting conditions, and medication were observed (see Table I). "]
[null,"Risk of bias judgement",null,null,"Low","The authors state that “patients were randomly allocated 1:1 according to a computer-generated allocation program code”.\r\n\r\nAlthough there was no mention of allocation sequence concealment, the fact that they used a computer-generated program code would prevent the enrolling investigator or the participant from having any knowledge of the forthcoming allocation.\r\nNo differences for TG and UC with respect to age, proportion of females, The Society of Thoracic Surgeons mortality risk score, NYHA class, prexisting conditions, and medication were observed (see Table I). "]
["Bias due to deviations from intended interventions","2.1.Were participants aware of their assigned intervention during the trial?",null,null,"Y","Given the nature of an exercise-based CR intervention, participants are aware of their intervention and it might therefore not be possible to blind them, their carers, or the people delivering this intervention."]
[null,"2.2.Were carers and people delivering the interventions aware of participants' assigned intervention during the trial?",null,null,"Y"]
[null,"2.3. If Y/PY/NI to 2.1 or 2.2: Were there deviations from the intended intervention that arose because of the experimental context?",null,null,"N","Although the authors do not specifically state if there were any deviations from the intended intervention, the flow of participants through the study (Fig 1 of 2016 paper) shows that no participant changed groups during the study and all changes to the intervention were either consistent with the intervention (i.e. drop out due to unrelated causes) or consistent with what could occur outside of the trial context (i.e. drop out due to unwillingness to continue participation)."]
[null,"2.4 If Y/PY to 2.3: Were these deviations likely to have affected the outcome?",null,null,"NA"]
[null,"2.5. If Y/PY/NI to 2.4: Were these deviations from intended intervention balanced between groups?",null,null,"NA"]
[null,"2.6 Was an appropriate analysis used to estimate the effect of assignment to intervention?",null,null,"Y","Data were tested for their distribution and the primary end point and key secondary outcomes were normally distributed; thus it was decided to present data as mean (SD). Baseline differences between groups were analyzed using the Student t test for independent samples for continuous variables and the Fisher exact test for categorical variables. Between-group differences in changes of the primary and secondary end points were analyzed using the Student t test for independent samples. For relevant effect sizes (mean differences between study groups), 95% CIs are presented. Because of the low number of dropouts that were all unrelated to the intervention and the primary intention of the study to evaluate efficacy and safety of exercise, a per-protocol analysis was performed. To account for observed differences in baseline parameters between the study groups, linear regression models using the change in the measure of interest as dependent variable and the study group as well as the baseline value of the measure of interest as independent variable were fit to the data. "]
[null,"2.7 If N/PN/NI to 2.6: Was there potential for a substantial impact (on the result) of the failure to analyse participants in the group to which they were randomized?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low","Given the nature of an exercise-based CR intervention, participants are aware of their intervention and it might therefore not be possible to blind them, their carers, or the people delivering this intervention.\r\nAlthough the authors do not specifically state if there were any deviations from the intended intervention, the flow of participants through the study (Fig 1 of 2016 paper) shows that no participant changed groups during the study and all changes to the intervention were either consistent with the intervention (i.e. drop out due to unrelated causes) or consistent with what could occur outside of the trial context (i.e. drop out due to unwillingness to continue participation).\r\n\r\n\r\nData were tested for their distribution and the primary end point and key secondary outcomes were normally distributed; thus it was decided to present data as mean (SD). Baseline differences between groups were analyzed using the Student t test for independent samples for continuous variables and the Fisher exact test for categorical variables. Between-group differences in changes of the primary and secondary end points were analyzed using the Student t test for independent samples. For relevant effect sizes (mean differences between study groups), 95% CIs are presented. Because of the low number of dropouts that were all unrelated to the intervention and the primary intention of the study to evaluate efficacy and safety of exercise, a per-protocol analysis was performed. To account for observed differences in baseline parameters between the study groups, linear regression models using the change in the measure of interest as dependent variable and the study group as well as the baseline value of the measure of interest as independent variable were fit to the data. \r\n"]
["Bias due to missing outcome data","3.1 Were data for this outcome available for all, or nearly all, participants randomized?",null,null,"N","Considering the fact that the appropriate study population for an analysis of the intention to treat effect is all randomized participants, in this Trial,  less than 95% of the participants in either the exercise group or the control group provided data for this outcome, as there were 3 overall drop outs (2/15 in exercise group and 1/15 in control group). "]
[null,"3.2 If N/PN/NI to 3.1: Is there evidence that result was not biased by missing outcome data?",null,null,"Y","Because of the low number of dropouts that were all unrelated to the intervention and the primary intention of the study to evaluate efficacy and safety of exercise, a per-protocol analysis was performed."]
[null,"3.3 If N/PN to 3.2: Could missingness in the outcome depend on its true value?",null,null,"NA"]
[null,"3.4 If Y/PY/NI to 3.3: Is it likely that missingness in the outcome depended on its true value?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low","Considering the fact that the appropriate study population for an analysis of the intention to treat effect is all randomized participants, in this Trial,  less than 95% of the participants in either the exercise group or the control group provided data for this outcome, as there were 3 overall drop outs (2/15 in exercise group and 1/15 in control group). \r\nBecause of the low number of dropouts that were all unrelated to the intervention and the primary intention of the study to evaluate efficacy and safety of exercise, a per-protocol analysis was performed.\r\n\r\n"]
["Bias in measurement of the outcome","4.1 Was the method of measuring the outcome inappropriate?",null,null,"N","HRQoL measured using SF36 and KCCQ both of which are validated questionnaires"]
[null,"4.2 Could measurement or ascertainment of the outcome have differed between intervention groups?",null,null,"N","Measurements were made in the same way for both intervention and control "]
[null,"4.3 Were outcome assessors aware of the intervention received by study participants?",null,null,"Y","The person reporting this outcome is the participant and they are aware of the intervention received. Collation and analysis of the results were most likely carried out by study personnel who were blinded to the intervention recived by the study participant."]
[null,"4.4 If Y/PY/NI to 4.3: Could assessment of the outcome have been influenced by knowledge of intervention received?",null,null,"Y","The assessment by the participants could have been affected by knowledge of the intervention as it is subjective. Exercise is generally believed to be a beneficial intervention in this patient group and it is possible that participants might have considered their HRQoL would be better if they had the intervention."]
[null,"4.5 If Y/PY/NI to 4.4: Is it likely that assessment of the outcome was influenced by knowledge of intervention received?",null,null,"PY"]
[null,"Risk of bias judgement",null,null,"High","HRQoL measured using SF36 and KCCQ both of which are validated questionnaires\r\nMeasurements were made in the same way for both intervention and control \r\nThe person reporting this outcome is the participant and they are aware of the intervention received. Collation and analysis of the results were most likely carried out by study personnel who were blinded to the intervention recived by the study participant.\r\nThe assessment by the participants could have been affected by knowledge of the intervention as it is subjective. Exercise is generally believed to be a beneficial intervention in this patient group and it is possible that participants might have considered their HRQoL would be better if they had the intervention.\r\n"]
["Bias in selection of the reported result","5.1 Were the data that produced this result analysed in accordance with a pre-specified analysis plan that was finalized before unblinded outcome data were available for analysis?",null,null,"Y","The trial was registered on clinicaltrials.gov before start of the study (NCT01935297) with researchers’ pre-specified intentions available in sufficient detail. There is no reason to believe that the data which produced this result was not analysed in accordance with a pre-specified analysis plan."]
[null,"5.2 ... multiple eligible outcome measurements (e.g. scales, definitions, time points) within the outcome domain?",null,null,"N","The authors provided results for all timepoints at which this outcome was assessed with all extra analysis intended as exploratory analysis to provide additional information on the group-specific impact of the intervention."]
[null,"5.3 ... multiple eligible analyses of the data?",null,null,"N","The authors reported all results. There is therefore no reason to believe that this result might have been selected from multiple eligible analyses of the data."]
[null,"Risk of bias judgement",null,null,"Low","The trial was registered on clinicaltrials.gov before start of the study (NCT01935297) with researchers’ pre-specified intentions available in sufficient detail. There is no reason to believe that the data which produced this result was not analysed in accordance with a pre-specified analysis plan.\r\nThe authors provided results for all timepoints at which this outcome was assessed with all extra analysis intended as exploratory analysis to provide additional information on the group-specific impact of the intervention.\r\nThe authors reported all results. There is therefore no reason to believe that this result might have been selected from multiple eligible analyses of the data."]
["Overall bias","Risk of bias judgement",null,null,"High","The authors state that “patients were randomly allocated 1:1 according to a computer-generated allocation program code”.\r\n\r\nAlthough there was no mention of allocation sequence concealment, the fact that they used a computer-generated program code would prevent the enrolling investigator or the participant from having any knowledge of the forthcoming allocation.\r\nNo differences for TG and UC with respect to age, proportion of females, The Society of Thoracic Surgeons mortality risk score, NYHA class, prexisting conditions, and medication were observed (see Table I). \r\nGiven the nature of an exercise-based CR intervention, participants are aware of their intervention and it might therefore not be possible to blind them, their carers, or the people delivering this intervention.\r\nAlthough the authors do not specifically state if there were any deviations from the intended intervention, the flow of participants through the study (Fig 1 of 2016 paper) shows that no participant changed groups during the study and all changes to the intervention were either consistent with the intervention (i.e. drop out due to unrelated causes) or consistent with what could occur outside of the trial context (i.e. drop out due to unwillingness to continue participation).\r\n\r\n\r\nData were tested for their distribution and the primary end point and key secondary outcomes were normally distributed; thus it was decided to present data as mean (SD). Baseline differences between groups were analyzed using the Student t test for independent samples for continuous variables and the Fisher exact test for categorical variables. Between-group differences in changes of the primary and secondary end points were analyzed using the Student t test for independent samples. For relevant effect sizes (mean differences between study groups), 95% CIs are presented. Because of the low number of dropouts that were all unrelated to the intervention and the primary intention of the study to evaluate efficacy and safety of exercise, a per-protocol analysis was performed. To account for observed differences in baseline parameters between the study groups, linear regression models using the change in the measure of interest as dependent variable and the study group as well as the baseline value of the measure of interest as independent variable were fit to the data. \r\n\r\nConsidering the fact that the appropriate study population for an analysis of the intention to treat effect is all randomized participants, in this Trial,  less than 95% of the participants in either the exercise group or the control group provided data for this outcome, as there were 3 overall drop outs. \r\nBecause of the low number of dropouts that were all unrelated to the intervention and the primary intention of the study to evaluate efficacy and safety of exercise, a per-protocol analysis was performed.\r\n\r\n\r\nHRQoL measured using SF36 and KCCQ both of which are validated questionnaires\r\nMeasurements were made in the same way for both intervention and control \r\nThe person reporting this outcome is the participant and they are aware of the intervention received. Collation and analysis of the results were most likely carried out by study personnel who were blinded to the intervention recived by the study participant.\r\nThe assessment by the participants could have been affected by knowledge of the intervention as it is subjective. Exercise is generally believed to be a beneficial intervention in this patient group and it is possible that participants might have considered their HRQoL would be better if they had the intervention.\r\n\r\nThe trial was registered on clinicaltrials.gov before start of the study (NCT01935297) with researchers’ pre-specified intentions available in sufficient detail. There is no reason to believe that the data which produced this result was not analysed in accordance with a pre-specified analysis plan.\r\nThe authors provided results for all timepoints at which this outcome was assessed with all extra analysis intended as exploratory analysis to provide additional information on the group-specific impact of the intervention.\r\nThe authors reported all results. There is therefore no reason to believe that this result might have been selected from multiple eligible analyses of the data."]
[]
[]
["Unique ID","3_C","Study ID","Sibilitz 2016","Assessor","LA"]
["Ref or Label","Heart 2016; 102: 1995-2003","Aim","assignment to intervention (the 'intention-to-treat' effect)\n\n"]
["Experimental","Exercise","Comparator","No Exercise","Source"]
["Outcome","HRQoL (PC at end of intervention)","Results","MD = -0.60 (95% CI -3.43, 2.23)","Weight",57.8]
["Domain","Signalling question",null,null,"Response","Comments"]
["Bias arising from the randomization process","1.1 Was the allocation sequence random?",null,null,"Y","The authors state that “Participants were allocated 1:1 to intervention or control using computer-generated allocation sequence with varying block sizes of 8, 6 and 4, concealed to the investigators by central telephone correspondence with the Copenhagen Trial Unit.”"]
[null,"1.2 Was the allocation sequence concealed until participants were enrolled and assigned to interventions?",null,null,"Y"]
[null,"1.3 Did baseline differences between intervention groups suggest a problem with the randomization process?",null,null,"N","“There was no evidence of baseline imbalances.” Table 1 shows good balance in patient characteristics between groups"]
[null,"Risk of bias judgement",null,null,"Low","The authors state that “Participants were allocated 1:1 to intervention or control using computer-generated allocation sequence with varying block sizes of 8, 6 and 4, concealed to the investigators by central telephone correspondence with the Copenhagen Trial Unit.”\r\n“There was no evidence of baseline imbalances.” Table 1 shows good balance in patient characteristics between groups"]
["Bias due to deviations from intended interventions","2.1.Were participants aware of their assigned intervention during the trial?",null,null,"Y","Given the nature of an exercise-based CR intervention, participants are aware of their intervention and it might therefore not be possible to blind them, their carers, or the people delivering this intervention."]
[null,"2.2.Were carers and people delivering the interventions aware of participants' assigned intervention during the trial?",null,null,"Y"]
[null,"2.3. If Y/PY/NI to 2.1 or 2.2: Were there deviations from the intended intervention that arose because of the experimental context?",null,null,"N","Although te authors do not expressesly mention if there were any deviations from the intended intervention, their CONSORT flow diagram of patients (fig 1 in article) shows that all participants were analysed in their initial intervention group."]
[null,"2.4 If Y/PY to 2.3: Were these deviations likely to have affected the outcome?",null,null,"NA"]
[null,"2.5. If Y/PY/NI to 2.4: Were these deviations from intended intervention balanced between groups?",null,null,"NA"]
[null,"2.6 Was an appropriate analysis used to estimate the effect of assignment to intervention?",null,null,"Y","The analysis was based on intention to treat using a mixed model with repeated measures (MMRM) and adjusted for the stratification variable of LVEF, ensuring that missing data will not create bias as long as the values are missing at random.25 The MMRM was used for continuous outcomes (both primary and secondary outcomes). This model assumes normally (Gaussian) distributed residuals. However, the residuals were not normally distributed for the primary outcome, and therefore transformed. We used log-transformation, and when log-transformation did not result in normally distributed residuals, we used Box–Cox transformation. In the MMRM we assumed correlation within the individual patient, but no correlation between patients. The fixed effects for the primary outcome were randomisation group, time, interaction between random and time and LVEF."]
[null,"2.7 If N/PN/NI to 2.6: Was there potential for a substantial impact (on the result) of the failure to analyse participants in the group to which they were randomized?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low","Given the nature of an exercise-based CR intervention, participants are aware of their intervention and it might therefore not be possible to blind them, their carers, or the people delivering this intervention.\r\nAlthough te authors do not expressesly mention if there were any deviations from the intended intervention, their CONSORT flow diagram of patients (fig 1 in article) shows that all participants were analysed in their initial intervention group.\r\n\r\n\r\nThe analysis was based on intention to treat using a mixed model with repeated measures (MMRM) and adjusted for the stratification variable of LVEF, ensuring that missing data will not create bias as long as the values are missing at random.25 The MMRM was used for continuous outcomes (both primary and secondary outcomes). This model assumes normally (Gaussian) distributed residuals. However, the residuals were not normally distributed for the primary outcome, and therefore transformed. We used log-transformation, and when log-transformation did not result in normally distributed residuals, we used Box–Cox transformation. In the MMRM we assumed correlation within the individual patient, but no correlation between patients. The fixed effects for the primary outcome were randomisation group, time, interaction between random and time and LVEF.\r\n"]
["Bias due to missing outcome data","3.1 Were data for this outcome available for all, or nearly all, participants randomized?",null,null,"N","Considering the fact that the appropriate study population for an analysis of the intention to treat effect is all randomized participants, in this Trial,  less than 95% of the participants in either the exercise group or the control group provided data for this outcome. The authors do state that the drop outs were due to complications after surgery and withdrawal of consent with 9 people dropping out of the study before completing 1 month of exercise training or usual care."]
[null,"3.2 If N/PN/NI to 3.1: Is there evidence that result was not biased by missing outcome data?",null,null,"N","There is no evidence to prove that the results was not biased by missing outcome data"]
[null,"3.3 If N/PN to 3.2: Could missingness in the outcome depend on its true value?",null,null,"PY","There is no considerable difference in the proportions of missing outcome data between the two groups.\r\nThe authors do state that the drop outs were due to complications after surgery and withdrawal of consent, but no mention was made to suggest that the intervention played a part in this withdrawal.\r\nReported reasons for missing outcome data are similar between both groups.\r\nThe circumstances of the trial do not make it likely that missingness in the outcome depends on its true value as more participants dropped out of the control group than from the exercise group."]
[null,"3.4 If Y/PY/NI to 3.3: Is it likely that missingness in the outcome depended on its true value?",null,null,"N"]
[null,"Risk of bias judgement",null,null,"Some concerns","Considering the fact that the appropriate study population for an analysis of the intention to treat effect is all randomized participants, in this Trial,  less than 95% of the participants in either the exercise group or the control group provided data for this outcome. The authors do state that the drop outs were due to complications after surgery and withdrawal of consent with 9 people dropping out of the study before completing 1 month of exercise training or usual care.\r\nThere is no evidence to prove that the results was not biased by missing outcome data\r\nThere is no considerable difference in the proportions of missing outcome data between the two groups.\r\nThe authors do state that the drop outs were due to complications after surgery and withdrawal of consent, but no mention was made to suggest that the intervention played a part in this withdrawal.\r\nReported reasons for missing outcome data are similar between both groups.\r\nThe circumstances of the trial do not make it likely that missingness in the outcome depends on its true value as more participants dropped out of the control group than from the exercise group.\r\n"]
["Bias in measurement of the outcome","4.1 Was the method of measuring the outcome inappropriate?",null,null,"N","HRQoL measured using SF36, a validated questionnaire"]
[null,"4.2 Could measurement or ascertainment of the outcome have differed between intervention groups?",null,null,"N","Measurements were made in the same way for both intervention and control "]
[null,"4.3 Were outcome assessors aware of the intervention received by study participants?",null,null,"Y","The person reporting this outcome is the participant and they are aware of the intervention they received. Collation and analysis of the results were most likely arried out by study personnel who were blinded. "]
[null,"4.4 If Y/PY/NI to 4.3: Could assessment of the outcome have been influenced by knowledge of intervention received?",null,null,"Y","“The trial applied central, stratified randomisation securing against selection bias, and blinded outcome assessment and blinded statistical analyses, reducing detection and interpretation bias”\r\nThe assessment by the participants could have been affected by knowledge of the intervention as it is subjective. Exercise is generally believed to be a beneficial intervention in this patient group and it is possible that participants might have considered their HRQoL would be better if they had the intervention."]
[null,"4.5 If Y/PY/NI to 4.4: Is it likely that assessment of the outcome was influenced by knowledge of intervention received?",null,null,"PY"]
[null,"Risk of bias judgement",null,null,"High","HRQoL measured using SF36, a validated questionnaire\r\nMeasurements were made in the same way for both intervention and control \r\nThe person reporting this outcome is the participant and they are aware of the intervention they received. Collation and analysis of the results were most likely arried out by study personnel who were blinded. \r\n“The trial applied central, stratified randomisation securing against selection bias, and blinded outcome assessment and blinded statistical analyses, reducing detection and interpretation bias”\r\nThe assessment by the participants could have been affected by knowledge of the intervention as it is subjective. Exercise is generally believed to be a beneficial intervention in this patient group and it is possible that participants might have considered their HRQoL would be better if they had the intervention.\r\n"]
["Bias in selection of the reported result","5.1 Were the data that produced this result analysed in accordance with a pre-specified analysis plan that was finalized before unblinded outcome data were available for analysis?",null,null,"Y","Trial registered on clinicaltrials.gov before start of the study  (NCT01558765) with researchers’ pre-specified intentions available in sufficient detail. There is therefore no reason to believe that the reults would not have been analysed in accordance with a pre-specified analysis plan."]
[null,"5.2 ... multiple eligible outcome measurements (e.g. scales, definitions, time points) within the outcome domain?",null,null,"N","The authors provided results for all timepoints at which this outcome was assessed within the scope of this article."]
[null,"5.3 ... multiple eligible analyses of the data?",null,null,"N","There is no evidence of multiple eligible analyses for this outcome."]
[null,"Risk of bias judgement",null,null,"Low","Trial registered on clinicaltrials.gov before start of the study  (NCT01558765) with researchers’ pre-specified intentions available in sufficient detail. There is therefore no reason to believe that the reults would not have been analysed in accordance with a pre-specified analysis plan.\r\nThe authors provided results for all timepoints at which this outcome was assessed within the scope of this article.\r\nThere is no evidence of multiple eligible analyses for this outcome."]
["Overall bias","Risk of bias judgement",null,null,"High","The authors state that “Participants were allocated 1:1 to intervention or control using computer-generated allocation sequence with varying block sizes of 8, 6 and 4, concealed to the investigators by central telephone correspondence with the Copenhagen Trial Unit.”\r\n“There was no evidence of baseline imbalances.” Table 1 shows good balance in patient characteristics between groups\r\nGiven the nature of an exercise-based CR intervention, participants are aware of their intervention and it might therefore not be possible to blind them, their carers, or the people delivering this intervention.\r\nAlthough te authors do not expressesly mention if there were any deviations from the intended intervention, their CONSORT flow diagram of patients (fig 1 in article) shows that all participants were analysed in their initial intervention group.\r\n\r\n\r\nThe analysis was based on intention to treat using a mixed model with repeated measures (MMRM) and adjusted for the stratification variable of LVEF, ensuring that missing data will not create bias as long as the values are missing at random.25 The MMRM was used for continuous outcomes (both primary and secondary outcomes). This model assumes normally (Gaussian) distributed residuals. However, the residuals were not normally distributed for the primary outcome, and therefore transformed. We used log-transformation, and when log-transformation did not result in normally distributed residuals, we used Box–Cox transformation. In the MMRM we assumed correlation within the individual patient, but no correlation between patients. The fixed effects for the primary outcome were randomisation group, time, interaction between random and time and LVEF.\r\n\r\nConsidering the fact that the appropriate study population for an analysis of the intention to treat effect is all randomized participants, in this Trial,  less than 95% of the participants in either the exercise group or the control group provided data for this outcome. The authors do state that the drop outs were due to complications after surgery and withdrawal of consent with 9 people dropping out of the study before completing 1 month of exercise training or usual care.\r\nThere is no evidence to prove that the results was not biased by missing outcome data\r\nThere is no considerable difference in the proportions of missing outcome data between the two groups.\r\nThe authors do state that the drop outs were due to complications after surgery and withdrawal of consent, but no mention was made to suggest that the intervention played a part in this withdrawal.\r\nReported reasons for missing outcome data are similar between both groups.\r\nThe circumstances of the trial do not make it likely that missingness in the outcome depends on its true value as more participants dropped out of the control group than from the exercise group.\r\n\r\nHRQoL measured using SF36, a validated questionnaire\r\nMeasurements were made in the same way for both intervention and control \r\nThe person reporting this outcome is the participant and they are aware of the intervention they received. Collation and analysis of the results were most likely arried out by study personnel who were blinded. \r\n“The trial applied central, stratified randomisation securing against selection bias, and blinded outcome assessment and blinded statistical analyses, reducing detection and interpretation bias”\r\nThe assessment by the participants could have been affected by knowledge of the intervention as it is subjective. Exercise is generally believed to be a beneficial intervention in this patient group and it is possible that participants might have considered their HRQoL would be better if they had the intervention.\r\n\r\nTrial registered on clinicaltrials.gov before start of the study  (NCT01558765) with researchers’ pre-specified intentions available in sufficient detail. There is therefore no reason to believe that the reults would not have been analysed in accordance with a pre-specified analysis plan.\r\nThe authors provided results for all timepoints at which this outcome was assessed within the scope of this article.\r\nThere is no evidence of multiple eligible analyses for this outcome."]
[]
[]
["Unique ID","2_D","Study ID","Pressler 2016","Assessor","LA"]
["Ref or Label","American Heart Journal vol 182; pp. 44-53","Aim","assignment to intervention (the 'intention-to-treat' effect)\n\n"]
["Experimental","Exercise","Comparator","No Exercise","Source"," Journal article(s)"]
["Outcome","HRQoL (MC at maximum follow up)","Results","MD = -1 (95% CI -11.27, 9.27)","Weight",10]
["Domain","Signalling question",null,null,"Response","Comments"]
["Bias arising from the randomization process","1.1 Was the allocation sequence random?",null,null,"Y","The authors state that “patients were randomly allocated 1:1 according to a computer-generated allocation program code”.\r\nAlthough there was no mention of allocation sequence concealment, the fact that they used a computer-generated program code would prevent the enrolling investigator or the participant from having any knowledge of the forthcoming allocation."]
[null,"1.2 Was the allocation sequence concealed until participants were enrolled and assigned to interventions?",null,null,"Y"]
[null,"1.3 Did baseline differences between intervention groups suggest a problem with the randomization process?",null,null,"N","No differences for TG and UC with respect to age, proportion of females, The Society of Thoracic Surgeons mortality risk score, NYHA class, prexisting conditions, and medication were observed (see Table I). "]
[null,"Risk of bias judgement",null,null,"Low","The authors state that “patients were randomly allocated 1:1 according to a computer-generated allocation program code”.\r\nAlthough there was no mention of allocation sequence concealment, the fact that they used a computer-generated program code would prevent the enrolling investigator or the participant from having any knowledge of the forthcoming allocation.\r\nNo differences for TG and UC with respect to age, proportion of females, The Society of Thoracic Surgeons mortality risk score, NYHA class, prexisting conditions, and medication were observed (see Table I). "]
["Bias due to deviations from intended interventions","2.1.Were participants aware of their assigned intervention during the trial?",null,null,"Y","Given the nature of an exercise-based CR intervention, participants are aware of their intervention and it might therefore not be possible to blind them, their carers, or the people delivering this intervention."]
[null,"2.2.Were carers and people delivering the interventions aware of participants' assigned intervention during the trial?",null,null,"Y"]
[null,"2.3. If Y/PY/NI to 2.1 or 2.2: Were there deviations from the intended intervention that arose because of the experimental context?",null,null,"N","Although the authors do not specifically state if there were any deviations from the intended intervention, the flow of participants through the study (Fig 1 of 2016 paper) shows that no participant changed groups during the study and all changes to the intervention were either consistent with the intervention (i.e. drop out due to unrelated causes) or consistent with what could occur outside of the trial context (i.e. drop out due to unwillingness to continue participation)."]
[null,"2.4 If Y/PY to 2.3: Were these deviations likely to have affected the outcome?",null,null,"NA"]
[null,"2.5. If Y/PY/NI to 2.4: Were these deviations from intended intervention balanced between groups?",null,null,"NA"]
[null,"2.6 Was an appropriate analysis used to estimate the effect of assignment to intervention?",null,null,"Y","Data were tested for their distribution and the primary end point and key secondary outcomes were normally distributed; thus it was decided to present data as mean (SD). Baseline differences between groups were analyzed using the Student t test for independent samples for continuous variables and the Fisher exact test for categorical variables. Between-group differences in changes of the primary and secondary end points were analyzed using the Student t test for independent samples. For relevant effect sizes (mean differences between study groups), 95% CIs are presented. Because of the low number of dropouts that were all unrelated to the intervention and the primary intention of the study to evaluate efficacy and safety of exercise, a per-protocol analysis was performed. To account for observed differences in baseline parameters between the study groups, linear regression models using the change in the measure of interest as dependent variable and the study group as well as the baseline value of the measure of interest as independent variable were fit to the data. "]
[null,"2.7 If N/PN/NI to 2.6: Was there potential for a substantial impact (on the result) of the failure to analyse participants in the group to which they were randomized?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low","Given the nature of an exercise-based CR intervention, participants are aware of their intervention and it might therefore not be possible to blind them, their carers, or the people delivering this intervention.\r\nAlthough the authors do not specifically state if there were any deviations from the intended intervention, the flow of participants through the study (Fig 1 of 2016 paper) shows that no participant changed groups during the study and all changes to the intervention were either consistent with the intervention (i.e. drop out due to unrelated causes) or consistent with what could occur outside of the trial context (i.e. drop out due to unwillingness to continue participation).\r\n\r\n\r\nData were tested for their distribution and the primary end point and key secondary outcomes were normally distributed; thus it was decided to present data as mean (SD). Baseline differences between groups were analyzed using the Student t test for independent samples for continuous variables and the Fisher exact test for categorical variables. Between-group differences in changes of the primary and secondary end points were analyzed using the Student t test for independent samples. For relevant effect sizes (mean differences between study groups), 95% CIs are presented. Because of the low number of dropouts that were all unrelated to the intervention and the primary intention of the study to evaluate efficacy and safety of exercise, a per-protocol analysis was performed. To account for observed differences in baseline parameters between the study groups, linear regression models using the change in the measure of interest as dependent variable and the study group as well as the baseline value of the measure of interest as independent variable were fit to the data. \r\n"]
["Bias due to missing outcome data","3.1 Were data for this outcome available for all, or nearly all, participants randomized?",null,null,"N","Considering the fact that the appropriate study population for an analysis of the intention to treat effect is all randomized participants, in this Trial,  less than 95% of the participants in either the exercise group or the control group provided data for this outcome. "]
[null,"3.2 If N/PN/NI to 3.1: Is there evidence that result was not biased by missing outcome data?",null,null,"N","There is no evidence to suggest that the result was not biased by missing outcome data"]
[null,"3.3 If N/PN to 3.2: Could missingness in the outcome depend on its true value?",null,null,"Y","Although reported reasons for missing outcome data are similar between both groups.There is no considerable difference in the proportions of missing outcome data between the two groups overall with 5 patient data missing from the exercise group and 8 patient data missing from the control group. Most of the missing data was due to death or other health conditions not necessarily related to the intervention. The circumstances of the trial do not make it likely that missingness in the outcome depends on its true value as more participants dropped out of the control group than from the exercise group."]
[null,"3.4 If Y/PY/NI to 3.3: Is it likely that missingness in the outcome depended on its true value?",null,null,"PN"]
[null,"Risk of bias judgement",null,null,"Some concerns","Considering the fact that the appropriate study population for an analysis of the intention to treat effect is all randomized participants, in this Trial,  less than 95% of the participants in either the exercise group or the control group provided data for this outcome, as there were 3 overall drop outs. \r\nThere is no evidence to suggest that the result was not biased by missing outcome data\r\nAlthough reported reasons for missing outcome data are similar between both groups.There is no considerable difference in the proportions of missing outcome data between the two groups overall with 5 patient data missing from the exercise group and 8 patient data missing from the control group. Most of the missing data was due to death or other health conditions not necessarily related to the intervention. The circumstances of the trial do not make it likely that missingness in the outcome depends on its true value as more participants dropped out of the control group than from the exercise group.\r\n"]
["Bias in measurement of the outcome","4.1 Was the method of measuring the outcome inappropriate?",null,null,"N","HRQoL measured using SF36 and KCCQ both of which are validated questionnaires"]
[null,"4.2 Could measurement or ascertainment of the outcome have differed between intervention groups?",null,null,"N","Measurements were made in the same way for both intervention and control "]
[null,"4.3 Were outcome assessors aware of the intervention received by study participants?",null,null,"Y","The person reporting this outcome is the participant and they are aware of the intervention received. Collation and analysis of the results were most likely carried out by study personnel who were blinded to the intervention recived by the study participant."]
[null,"4.4 If Y/PY/NI to 4.3: Could assessment of the outcome have been influenced by knowledge of intervention received?",null,null,"Y","The assessment by the participants could have been affected by knowledge of the intervention as it is subjective. Exercise is generally believed to be a beneficial intervention in this patient group and it is possible that participants might have considered their HRQoL would be better if they had the intervention."]
[null,"4.5 If Y/PY/NI to 4.4: Is it likely that assessment of the outcome was influenced by knowledge of intervention received?",null,null,"PY"]
[null,"Risk of bias judgement",null,null,"High","HRQoL measured using SF36 and KCCQ both of which are validated questionnaires\r\nMeasurements were made in the same way for both intervention and control \r\nThe person reporting this outcome is the participant and they are aware of the intervention received. Collation and analysis of the results were most likely carried out by study personnel who were blinded to the intervention recived by the study participant.\r\nThe assessment by the participants could have been affected by knowledge of the intervention as it is subjective. Exercise is generally believed to be a beneficial intervention in this patient group and it is possible that participants might have considered their HRQoL would be better if they had the intervention.\r\n"]
["Bias in selection of the reported result","5.1 Were the data that produced this result analysed in accordance with a pre-specified analysis plan that was finalized before unblinded outcome data were available for analysis?",null,null,"Y","The trial was registered on clinicaltrials.gov before start of the study (NCT01935297) with researchers’ pre-specified intentions available in sufficient detail. There is no reason to believe that the data which produced this result was not analysed in accordance with a pre-specified analysis plan."]
[null,"5.2 ... multiple eligible outcome measurements (e.g. scales, definitions, time points) within the outcome domain?",null,null,"N","The authors provided results for all timepoints at which this outcome was assessed with all extra analysis intended as exploratory analysis to provide additional information on the group-specific impact of the intervention."]
[null,"5.3 ... multiple eligible analyses of the data?",null,null,"N","The authors reported all results. There is therefore no reason to believe that this result might have been selected from multiple eligible analyses of the data."]
[null,"Risk of bias judgement",null,null,"Low","The trial was registered on clinicaltrials.gov before start of the study (NCT01935297) with researchers’ pre-specified intentions available in sufficient detail. There is no reason to believe that the data which produced this result was not analysed in accordance with a pre-specified analysis plan.\r\nThe authors provided results for all timepoints at which this outcome was assessed with all extra analysis intended as exploratory analysis to provide additional information on the group-specific impact of the intervention.\r\nThe authors reported all results. There is therefore no reason to believe that this result might have been selected from multiple eligible analyses of the data."]
["Overall bias","Risk of bias judgement",null,null,"High","The authors state that “patients were randomly allocated 1:1 according to a computer-generated allocation program code”.\r\nAlthough there was no mention of allocation sequence concealment, the fact that they used a computer-generated program code would prevent the enrolling investigator or the participant from having any knowledge of the forthcoming allocation.\r\nNo differences for TG and UC with respect to age, proportion of females, The Society of Thoracic Surgeons mortality risk score, NYHA class, prexisting conditions, and medication were observed (see Table I). \r\nGiven the nature of an exercise-based CR intervention, participants are aware of their intervention and it might therefore not be possible to blind them, their carers, or the people delivering this intervention.\r\nAlthough the authors do not specifically state if there were any deviations from the intended intervention, the flow of participants through the study (Fig 1 of 2016 paper) shows that no participant changed groups during the study and all changes to the intervention were either consistent with the intervention (i.e. drop out due to unrelated causes) or consistent with what could occur outside of the trial context (i.e. drop out due to unwillingness to continue participation).\r\n\r\n\r\nData were tested for their distribution and the primary end point and key secondary outcomes were normally distributed; thus it was decided to present data as mean (SD). Baseline differences between groups were analyzed using the Student t test for independent samples for continuous variables and the Fisher exact test for categorical variables. Between-group differences in changes of the primary and secondary end points were analyzed using the Student t test for independent samples. For relevant effect sizes (mean differences between study groups), 95% CIs are presented. Because of the low number of dropouts that were all unrelated to the intervention and the primary intention of the study to evaluate efficacy and safety of exercise, a per-protocol analysis was performed. To account for observed differences in baseline parameters between the study groups, linear regression models using the change in the measure of interest as dependent variable and the study group as well as the baseline value of the measure of interest as independent variable were fit to the data. \r\n\r\nConsidering the fact that the appropriate study population for an analysis of the intention to treat effect is all randomized participants, in this Trial,  less than 95% of the participants in either the exercise group or the control group provided data for this outcome, as there were 3 overall drop outs. \r\nThere is no evidence to suggest that the result was not biased by missing outcome data\r\nAlthough reported reasons for missing outcome data are similar between both groups.There is no considerable difference in the proportions of missing outcome data between the two groups overall with 5 patient data missing from the exercise group and 8 patient data missing from the control group. Most of the missing data was due to death or other health conditions not necessarily related to the intervention. The circumstances of the trial do not make it likely that missingness in the outcome depends on its true value as more participants dropped out of the control group than from the exercise group.\r\n\r\nHRQoL measured using SF36 and KCCQ both of which are validated questionnaires\r\nMeasurements were made in the same way for both intervention and control \r\nThe person reporting this outcome is the participant and they are aware of the intervention received. Collation and analysis of the results were most likely carried out by study personnel who were blinded to the intervention recived by the study participant.\r\nThe assessment by the participants could have been affected by knowledge of the intervention as it is subjective. Exercise is generally believed to be a beneficial intervention in this patient group and it is possible that participants might have considered their HRQoL would be better if they had the intervention.\r\n\r\nThe trial was registered on clinicaltrials.gov before start of the study (NCT01935297) with researchers’ pre-specified intentions available in sufficient detail. There is no reason to believe that the data which produced this result was not analysed in accordance with a pre-specified analysis plan.\r\nThe authors provided results for all timepoints at which this outcome was assessed with all extra analysis intended as exploratory analysis to provide additional information on the group-specific impact of the intervention.\r\nThe authors reported all results. There is therefore no reason to believe that this result might have been selected from multiple eligible analyses of the data."]
[]
[]
["Unique ID","3_D","Study ID","Sibilitz 2016","Assessor","LA"]
["Ref or Label","Heart 2016; 102: 1995-2003","Aim","assignment to intervention (the 'intention-to-treat' effect)\n\n"]
["Experimental","Exercise","Comparator","No Exercise","Source"," Journal article(s)"]
["Outcome","HRQoL (MC at maximum follow up)","Results","MD = -1.5 (95% CI -4.93, 1.93)","Weight",90]
["Domain","Signalling question",null,null,"Response","Comments"]
["Bias arising from the randomization process","1.1 Was the allocation sequence random?",null,null,"Y","The authors state that “Participants were allocated 1:1 to intervention or control using computer-generated allocation sequence with varying block sizes of 8, 6 and 4, concealed to the investigators by central telephone correspondence with the Copenhagen Trial Unit.”"]
[null,"1.2 Was the allocation sequence concealed until participants were enrolled and assigned to interventions?",null,null,"Y"]
[null,"1.3 Did baseline differences between intervention groups suggest a problem with the randomization process?",null,null,"N","“There was no evidence of baseline imbalances.” Table 1 shows good balance in patient characteristics between groups"]
[null,"Risk of bias judgement",null,null,"Low","The authors state that “Participants were allocated 1:1 to intervention or control using computer-generated allocation sequence with varying block sizes of 8, 6 and 4, concealed to the investigators by central telephone correspondence with the Copenhagen Trial Unit.”\r\n“There was no evidence of baseline imbalances.” Table 1 shows good balance in patient characteristics between groups"]
["Bias due to deviations from intended interventions","2.1.Were participants aware of their assigned intervention during the trial?",null,null,"Y","Given the nature of an exercise-based CR intervention, participants are aware of their intervention and it might therefore not be possible to blind them, their carers, or the people delivering this intervention."]
[null,"2.2.Were carers and people delivering the interventions aware of participants' assigned intervention during the trial?",null,null,"Y"]
[null,"2.3. If Y/PY/NI to 2.1 or 2.2: Were there deviations from the intended intervention that arose because of the experimental context?",null,null,"N","Although te authors do not expressesly mention if there were any deviations from the intended intervention, their CONSORT flow diagram of patients (fig 1 in article) shows that all participants were analysed in their initial intervention group."]
[null,"2.4 If Y/PY to 2.3: Were these deviations likely to have affected the outcome?",null,null,"NA"]
[null,"2.5. If Y/PY/NI to 2.4: Were these deviations from intended intervention balanced between groups?",null,null,"NA"]
[null,"2.6 Was an appropriate analysis used to estimate the effect of assignment to intervention?",null,null,"Y","The analysis was based on intention to treat using a mixed model with repeated measures (MMRM) and adjusted for the stratification variable of LVEF, ensuring that missing data will not create bias as long as the values are missing at random.25 The MMRM was used for continuous outcomes (both primary and secondary outcomes). This model assumes normally (Gaussian) distributed residuals. However, the residuals were not normally distributed for the primary outcome, and therefore transformed. We used log-transformation, and when log-transformation did not result in normally distributed residuals, we used Box–Cox transformation. In the MMRM we assumed correlation within the individual patient, but no correlation between patients. The fixed effects for the primary outcome were randomisation group, time, interaction between random and time and LVEF."]
[null,"2.7 If N/PN/NI to 2.6: Was there potential for a substantial impact (on the result) of the failure to analyse participants in the group to which they were randomized?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low","Given the nature of an exercise-based CR intervention, participants are aware of their intervention and it might therefore not be possible to blind them, their carers, or the people delivering this intervention.\r\nAlthough te authors do not expressesly mention if there were any deviations from the intended intervention, their CONSORT flow diagram of patients (fig 1 in article) shows that all participants were analysed in their initial intervention group.\r\n\r\n\r\nThe analysis was based on intention to treat using a mixed model with repeated measures (MMRM) and adjusted for the stratification variable of LVEF, ensuring that missing data will not create bias as long as the values are missing at random.25 The MMRM was used for continuous outcomes (both primary and secondary outcomes). This model assumes normally (Gaussian) distributed residuals. However, the residuals were not normally distributed for the primary outcome, and therefore transformed. We used log-transformation, and when log-transformation did not result in normally distributed residuals, we used Box–Cox transformation. In the MMRM we assumed correlation within the individual patient, but no correlation between patients. The fixed effects for the primary outcome were randomisation group, time, interaction between random and time and LVEF.\r\n"]
["Bias due to missing outcome data","3.1 Were data for this outcome available for all, or nearly all, participants randomized?",null,null,"N","Considering the fact that the appropriate study population for an analysis of the intention to treat effect is all randomized participants, in this Trial,  less than 95% of the participants in either the exercise group or the control group provided data for this outcome. The authors do state that the drop outs were due to complications after surgery and withdrawal of consent with 9 people dropping out of the study before completing 1 month of exercise training or usual care."]
[null,"3.2 If N/PN/NI to 3.1: Is there evidence that result was not biased by missing outcome data?",null,null,"N","There is no evidence to prove that the results was not biased by missing outcome data"]
[null,"3.3 If N/PN to 3.2: Could missingness in the outcome depend on its true value?",null,null,"Y","There is no considerable difference in the proportions of missing outcome data between the two groups.\r\nThe authors do state that the drop outs were due to complications after surgery and withdrawal of consent, but no mention was made to suggest that the intervention played a part in this withdrawal.\r\nReported reasons for missing outcome data are similar between both groups.\r\nThe circumstances of the trial do not make it likely that missingness in the outcome depends on its true value as more participants dropped out of the control group than from the exercise group."]
[null,"3.4 If Y/PY/NI to 3.3: Is it likely that missingness in the outcome depended on its true value?",null,null,"PN"]
[null,"Risk of bias judgement",null,null,"Some concerns","Considering the fact that the appropriate study population for an analysis of the intention to treat effect is all randomized participants, in this Trial,  less than 95% of the participants in either the exercise group or the control group provided data for this outcome. The authors do state that the drop outs were due to complications after surgery and withdrawal of consent with 9 people dropping out of the study before completing 1 month of exercise training or usual care.\r\nThere is no evidence to prove that the results was not biased by missing outcome data\r\nThere is no considerable difference in the proportions of missing outcome data between the two groups.\r\nThe authors do state that the drop outs were due to complications after surgery and withdrawal of consent, but no mention was made to suggest that the intervention played a part in this withdrawal.\r\nReported reasons for missing outcome data are similar between both groups.\r\nThe circumstances of the trial do not make it likely that missingness in the outcome depends on its true value as more participants dropped out of the control group than from the exercise group.\r\n"]
["Bias in measurement of the outcome","4.1 Was the method of measuring the outcome inappropriate?",null,null,"N","HRQoL measured using SF36, a validated questionnaire"]
[null,"4.2 Could measurement or ascertainment of the outcome have differed between intervention groups?",null,null,"N","Measurements were made in the same way for both intervention and control "]
[null,"4.3 Were outcome assessors aware of the intervention received by study participants?",null,null,"Y","The person reporting this outcome is the participant and they are aware of the intervention they received. Collation and analysis of the results were most likely arried out by study personnel who were blinded. "]
[null,"4.4 If Y/PY/NI to 4.3: Could assessment of the outcome have been influenced by knowledge of intervention received?",null,null,"Y","“The trial applied central, stratified randomisation securing against selection bias, and blinded outcome assessment and blinded statistical analyses, reducing detection and interpretation bias”\r\nThe assessment by the participants could have been affected by knowledge of the intervention as it is subjective. Exercise is generally believed to be a beneficial intervention in this patient group and it is possible that participants might have considered their HRQoL would be better if they had the intervention."]
[null,"4.5 If Y/PY/NI to 4.4: Is it likely that assessment of the outcome was influenced by knowledge of intervention received?",null,null,"PY"]
[null,"Risk of bias judgement",null,null,"High","HRQoL measured using SF36, a validated questionnaire\r\nMeasurements were made in the same way for both intervention and control \r\nThe person reporting this outcome is the participant and they are aware of the intervention they received. Collation and analysis of the results were most likely arried out by study personnel who were blinded. \r\n“The trial applied central, stratified randomisation securing against selection bias, and blinded outcome assessment and blinded statistical analyses, reducing detection and interpretation bias”\r\nThe assessment by the participants could have been affected by knowledge of the intervention as it is subjective. Exercise is generally believed to be a beneficial intervention in this patient group and it is possible that participants might have considered their HRQoL would be better if they had the intervention.\r\n"]
["Bias in selection of the reported result","5.1 Were the data that produced this result analysed in accordance with a pre-specified analysis plan that was finalized before unblinded outcome data were available for analysis?",null,null,"Y","Trial registered on clinicaltrials.gov before start of the study  (NCT01558765) with researchers’ pre-specified intentions available in sufficient detail. There is therefore no reason to believe that the reults would not have been analysed in accordance with a pre-specified analysis plan."]
[null,"5.2 ... multiple eligible outcome measurements (e.g. scales, definitions, time points) within the outcome domain?",null,null,"N","The authors provided results for all timepoints at which this outcome was assessed within the scope of this article."]
[null,"5.3 ... multiple eligible analyses of the data?",null,null,"N","There is no evidence of multiple eligible analyses for this outcome."]
[null,"Risk of bias judgement",null,null,"Low","Trial registered on clinicaltrials.gov before start of the study  (NCT01558765) with researchers’ pre-specified intentions available in sufficient detail. There is therefore no reason to believe that the reults would not have been analysed in accordance with a pre-specified analysis plan.\r\nThe authors provided results for all timepoints at which this outcome was assessed within the scope of this article.\r\nThere is no evidence of multiple eligible analyses for this outcome."]
["Overall bias","Risk of bias judgement",null,null,"High","The authors state that “Participants were allocated 1:1 to intervention or control using computer-generated allocation sequence with varying block sizes of 8, 6 and 4, concealed to the investigators by central telephone correspondence with the Copenhagen Trial Unit.”\r\n“There was no evidence of baseline imbalances.” Table 1 shows good balance in patient characteristics between groups\r\nGiven the nature of an exercise-based CR intervention, participants are aware of their intervention and it might therefore not be possible to blind them, their carers, or the people delivering this intervention.\r\nAlthough te authors do not expressesly mention if there were any deviations from the intended intervention, their CONSORT flow diagram of patients (fig 1 in article) shows that all participants were analysed in their initial intervention group.\r\n\r\n\r\nThe analysis was based on intention to treat using a mixed model with repeated measures (MMRM) and adjusted for the stratification variable of LVEF, ensuring that missing data will not create bias as long as the values are missing at random.25 The MMRM was used for continuous outcomes (both primary and secondary outcomes). This model assumes normally (Gaussian) distributed residuals. However, the residuals were not normally distributed for the primary outcome, and therefore transformed. We used log-transformation, and when log-transformation did not result in normally distributed residuals, we used Box–Cox transformation. In the MMRM we assumed correlation within the individual patient, but no correlation between patients. The fixed effects for the primary outcome were randomisation group, time, interaction between random and time and LVEF.\r\n\r\nConsidering the fact that the appropriate study population for an analysis of the intention to treat effect is all randomized participants, in this Trial,  less than 95% of the participants in either the exercise group or the control group provided data for this outcome. The authors do state that the drop outs were due to complications after surgery and withdrawal of consent with 9 people dropping out of the study before completing 1 month of exercise training or usual care.\r\nThere is no evidence to prove that the results was not biased by missing outcome data\r\nThere is no considerable difference in the proportions of missing outcome data between the two groups.\r\nThe authors do state that the drop outs were due to complications after surgery and withdrawal of consent, but no mention was made to suggest that the intervention played a part in this withdrawal.\r\nReported reasons for missing outcome data are similar between both groups.\r\nThe circumstances of the trial do not make it likely that missingness in the outcome depends on its true value as more participants dropped out of the control group than from the exercise group.\r\n\r\nHRQoL measured using SF36, a validated questionnaire\r\nMeasurements were made in the same way for both intervention and control \r\nThe person reporting this outcome is the participant and they are aware of the intervention they received. Collation and analysis of the results were most likely arried out by study personnel who were blinded. \r\n“The trial applied central, stratified randomisation securing against selection bias, and blinded outcome assessment and blinded statistical analyses, reducing detection and interpretation bias”\r\nThe assessment by the participants could have been affected by knowledge of the intervention as it is subjective. Exercise is generally believed to be a beneficial intervention in this patient group and it is possible that participants might have considered their HRQoL would be better if they had the intervention.\r\n\r\nTrial registered on clinicaltrials.gov before start of the study  (NCT01558765) with researchers’ pre-specified intentions available in sufficient detail. There is therefore no reason to believe that the reults would not have been analysed in accordance with a pre-specified analysis plan.\r\nThe authors provided results for all timepoints at which this outcome was assessed within the scope of this article.\r\nThere is no evidence of multiple eligible analyses for this outcome."]
[]
[]
["Unique ID","3_E","Study ID","Sibilitz 2016","Assessor","LA"]
["Ref or Label","Heart 2016; 102: 1995-2003","Aim","assignment to intervention (the 'intention-to-treat' effect)\n\n"]
["Experimental","Exercise","Comparator","No Exercise","Source"," Journal article(s)"]
["Outcome","HRQoL (PC at maximum follow up)","Results","MD = -1 (95% CI -3.79, 1.79)","Weight",93.8]
["Domain","Signalling question",null,null,"Response","Comments"]
["Bias arising from the randomization process","1.1 Was the allocation sequence random?",null,null,"Y","The authors state that “Participants were allocated 1:1 to intervention or control using computer-generated allocation sequence with varying block sizes of 8, 6 and 4, concealed to the investigators by central telephone correspondence with the Copenhagen Trial Unit.”\r\n"]
[null,"1.2 Was the allocation sequence concealed until participants were enrolled and assigned to interventions?",null,null,"Y"]
[null,"1.3 Did baseline differences between intervention groups suggest a problem with the randomization process?",null,null,"N","“There was no evidence of baseline imbalances.” Table 1 shows good balance in patient characteristics between groups"]
[null,"Risk of bias judgement",null,null,"Low","The authors state that “Participants were allocated 1:1 to intervention or control using computer-generated allocation sequence with varying block sizes of 8, 6 and 4, concealed to the investigators by central telephone correspondence with the Copenhagen Trial Unit.”\r\n\r\n“There was no evidence of baseline imbalances.” Table 1 shows good balance in patient characteristics between groups"]
["Bias due to deviations from intended interventions","2.1.Were participants aware of their assigned intervention during the trial?",null,null,"Y","Given the nature of an exercise-based CR intervention, participants are aware of their intervention and it might therefore not be possible to blind them, their carers, or the people delivering this intervention.\r\n"]
[null,"2.2.Were carers and people delivering the interventions aware of participants' assigned intervention during the trial?",null,null,"Y"]
[null,"2.3. If Y/PY/NI to 2.1 or 2.2: Were there deviations from the intended intervention that arose because of the experimental context?",null,null,"N","Although te authors do not expressesly mention if there were any deviations from the intended intervention, their CONSORT flow diagram of patients (fig 1 in article) shows that all participants were analysed in their initial intervention group."]
[null,"2.4 If Y/PY to 2.3: Were these deviations likely to have affected the outcome?",null,null,"NA"]
[null,"2.5. If Y/PY/NI to 2.4: Were these deviations from intended intervention balanced between groups?",null,null,"NA"]
[null,"2.6 Was an appropriate analysis used to estimate the effect of assignment to intervention?",null,null,"Y","The analysis was based on intention to treat using a mixed model with repeated measures (MMRM) and adjusted for the stratification variable of LVEF, ensuring that missing data will not create bias as long as the values are missing at random.25 The MMRM was used for continuous outcomes (both primary and secondary outcomes). This model assumes normally (Gaussian) distributed residuals. However, the residuals were not normally distributed for the primary outcome, and therefore transformed. We used log-transformation, and when log-transformation did not result in normally distributed residuals, we used Box–Cox transformation. In the MMRM we assumed correlation within the individual patient, but no correlation between patients. The fixed effects for the primary outcome were randomisation group, time, interaction between random and time and LVEF."]
[null,"2.7 If N/PN/NI to 2.6: Was there potential for a substantial impact (on the result) of the failure to analyse participants in the group to which they were randomized?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low","Given the nature of an exercise-based CR intervention, participants are aware of their intervention and it might therefore not be possible to blind them, their carers, or the people delivering this intervention.\r\n\r\nAlthough te authors do not expressesly mention if there were any deviations from the intended intervention, their CONSORT flow diagram of patients (fig 1 in article) shows that all participants were analysed in their initial intervention group.\r\n\r\n\r\nThe analysis was based on intention to treat using a mixed model with repeated measures (MMRM) and adjusted for the stratification variable of LVEF, ensuring that missing data will not create bias as long as the values are missing at random.25 The MMRM was used for continuous outcomes (both primary and secondary outcomes). This model assumes normally (Gaussian) distributed residuals. However, the residuals were not normally distributed for the primary outcome, and therefore transformed. We used log-transformation, and when log-transformation did not result in normally distributed residuals, we used Box–Cox transformation. In the MMRM we assumed correlation within the individual patient, but no correlation between patients. The fixed effects for the primary outcome were randomisation group, time, interaction between random and time and LVEF.\r\n"]
["Bias due to missing outcome data","3.1 Were data for this outcome available for all, or nearly all, participants randomized?",null,null,"N","Considering the fact that the appropriate study population for an analysis of the intention to treat effect is all randomized participants, in this Trial,  less than 95% of the participants in either the exercise group or the control group provided data for this outcome. The authors do state that the drop outs were due to complications after surgery and withdrawal of consent with 9 people dropping out of the study before completing 1 month of exercise training or usual care."]
[null,"3.2 If N/PN/NI to 3.1: Is there evidence that result was not biased by missing outcome data?",null,null,"N","There is no evidence to prove that the results was not biased by missing outcome data"]
[null,"3.3 If N/PN to 3.2: Could missingness in the outcome depend on its true value?",null,null,"Y","There is no considerable difference in the proportions of missing outcome data between the two groups.\r\nThe authors do state that the drop outs were due to complications after surgery and withdrawal of consent, but no mention was made to suggest that the intervention played a part in this withdrawal.\r\nReported reasons for missing outcome data are similar between both groups.\r\nThe circumstances of the trial do not make it likely that missingness in the outcome depends on its true value as more participants dropped out of the control group than from the exercise group.\r\n"]
[null,"3.4 If Y/PY/NI to 3.3: Is it likely that missingness in the outcome depended on its true value?",null,null,"PN"]
[null,"Risk of bias judgement",null,null,"Some concerns","Considering the fact that the appropriate study population for an analysis of the intention to treat effect is all randomized participants, in this Trial,  less than 95% of the participants in either the exercise group or the control group provided data for this outcome. The authors do state that the drop outs were due to complications after surgery and withdrawal of consent with 9 people dropping out of the study before completing 1 month of exercise training or usual care.\r\nThere is no evidence to prove that the results was not biased by missing outcome data\r\nThere is no considerable difference in the proportions of missing outcome data between the two groups.\r\nThe authors do state that the drop outs were due to complications after surgery and withdrawal of consent, but no mention was made to suggest that the intervention played a part in this withdrawal.\r\nReported reasons for missing outcome data are similar between both groups.\r\nThe circumstances of the trial do not make it likely that missingness in the outcome depends on its true value as more participants dropped out of the control group than from the exercise group.\r\n\r\n"]
["Bias in measurement of the outcome","4.1 Was the method of measuring the outcome inappropriate?",null,null,"N","HRQoL measured using SF36, a validated questionnaire"]
[null,"4.2 Could measurement or ascertainment of the outcome have differed between intervention groups?",null,null,"N","Measurements were made in the same way for both intervention and control "]
[null,"4.3 Were outcome assessors aware of the intervention received by study participants?",null,null,"Y","The person reporting this outcome is the participant and they are aware of the intervention they received. Collation and analysis of the results were most likely arried out by study personnel who were blinded. \r\n“The trial applied central, stratified randomisation securing against selection bias, and blinded outcome assessment and blinded statistical analyses, reducing detection and interpretation bias”"]
[null,"4.4 If Y/PY/NI to 4.3: Could assessment of the outcome have been influenced by knowledge of intervention received?",null,null,"Y","\r\nThe assessment by the participants could have been affected by knowledge of the intervention as it is subjective. Exercise is generally believed to be a beneficial intervention in this patient group and it is possible that participants might have considered their HRQoL would be better if they had the intervention.\r\n"]
[null,"4.5 If Y/PY/NI to 4.4: Is it likely that assessment of the outcome was influenced by knowledge of intervention received?",null,null,"PY"]
[null,"Risk of bias judgement",null,null,"High","HRQoL measured using SF36, a validated questionnaire\r\nMeasurements were made in the same way for both intervention and control \r\nThe person reporting this outcome is the participant and they are aware of the intervention they received. Collation and analysis of the results were most likely arried out by study personnel who were blinded. \r\n“The trial applied central, stratified randomisation securing against selection bias, and blinded outcome assessment and blinded statistical analyses, reducing detection and interpretation bias”The assessment by the participants could have been affected by knowledge of the intervention as it is subjective. Exercise is generally believed to be a beneficial intervention in this patient group and it is possible that participants might have considered their HRQoL would be better if they had the intervention.\r\n\r\n"]
["Bias in selection of the reported result","5.1 Were the data that produced this result analysed in accordance with a pre-specified analysis plan that was finalized before unblinded outcome data were available for analysis?",null,null,"Y","Trial registered on clinicaltrials.gov before start of the study  (NCT01558765) with researchers’ pre-specified intentions available in sufficient detail. There is therefore no reason to believe that the reults would not have been analysed in accordance with a pre-specified analysis plan."]
[null,"5.2 ... multiple eligible outcome measurements (e.g. scales, definitions, time points) within the outcome domain?",null,null,"N","The authors provided results for all timepoints at which this outcome was assessed within the scope of this article."]
[null,"5.3 ... multiple eligible analyses of the data?",null,null,"N","There is no evidence of multiple eligible analyses for this outcome."]
[null,"Risk of bias judgement",null,null,"Low","Trial registered on clinicaltrials.gov before start of the study  (NCT01558765) with researchers’ pre-specified intentions available in sufficient detail. There is therefore no reason to believe that the reults would not have been analysed in accordance with a pre-specified analysis plan.\r\nThe authors provided results for all timepoints at which this outcome was assessed within the scope of this article.\r\nThere is no evidence of multiple eligible analyses for this outcome."]
["Overall bias","Risk of bias judgement",null,null,"High","The authors state that “Participants were allocated 1:1 to intervention or control using computer-generated allocation sequence with varying block sizes of 8, 6 and 4, concealed to the investigators by central telephone correspondence with the Copenhagen Trial Unit.”\r\n\r\n“There was no evidence of baseline imbalances.” Table 1 shows good balance in patient characteristics between groups\r\nGiven the nature of an exercise-based CR intervention, participants are aware of their intervention and it might therefore not be possible to blind them, their carers, or the people delivering this intervention.\r\n\r\nAlthough te authors do not expressesly mention if there were any deviations from the intended intervention, their CONSORT flow diagram of patients (fig 1 in article) shows that all participants were analysed in their initial intervention group.\r\n\r\n\r\nThe analysis was based on intention to treat using a mixed model with repeated measures (MMRM) and adjusted for the stratification variable of LVEF, ensuring that missing data will not create bias as long as the values are missing at random.25 The MMRM was used for continuous outcomes (both primary and secondary outcomes). This model assumes normally (Gaussian) distributed residuals. However, the residuals were not normally distributed for the primary outcome, and therefore transformed. We used log-transformation, and when log-transformation did not result in normally distributed residuals, we used Box–Cox transformation. In the MMRM we assumed correlation within the individual patient, but no correlation between patients. The fixed effects for the primary outcome were randomisation group, time, interaction between random and time and LVEF.\r\n\r\nConsidering the fact that the appropriate study population for an analysis of the intention to treat effect is all randomized participants, in this Trial,  less than 95% of the participants in either the exercise group or the control group provided data for this outcome. The authors do state that the drop outs were due to complications after surgery and withdrawal of consent with 9 people dropping out of the study before completing 1 month of exercise training or usual care.\r\nThere is no evidence to prove that the results was not biased by missing outcome data\r\nThere is no considerable difference in the proportions of missing outcome data between the two groups.\r\nThe authors do state that the drop outs were due to complications after surgery and withdrawal of consent, but no mention was made to suggest that the intervention played a part in this withdrawal.\r\nReported reasons for missing outcome data are similar between both groups.\r\nThe circumstances of the trial do not make it likely that missingness in the outcome depends on its true value as more participants dropped out of the control group than from the exercise group.\r\n\r\n\r\nHRQoL measured using SF36, a validated questionnaire\r\nMeasurements were made in the same way for both intervention and control \r\nThe person reporting this outcome is the participant and they are aware of the intervention they received. Collation and analysis of the results were most likely arried out by study personnel who were blinded. \r\n“The trial applied central, stratified randomisation securing against selection bias, and blinded outcome assessment and blinded statistical analyses, reducing detection and interpretation bias”The assessment by the participants could have been affected by knowledge of the intervention as it is subjective. Exercise is generally believed to be a beneficial intervention in this patient group and it is possible that participants might have considered their HRQoL would be better if they had the intervention.\r\n\r\n\r\nTrial registered on clinicaltrials.gov before start of the study  (NCT01558765) with researchers’ pre-specified intentions available in sufficient detail. There is therefore no reason to believe that the reults would not have been analysed in accordance with a pre-specified analysis plan.\r\nThe authors provided results for all timepoints at which this outcome was assessed within the scope of this article.\r\nThere is no evidence of multiple eligible analyses for this outcome."]
[]
[]
["Unique ID","2_E","Study ID","Pressler 2016","Assessor","LA"]
["Ref or Label","American Heart Journal vol 182; pp. 44-53","Aim","assignment to intervention (the 'intention-to-treat' effect)\n\n"]
["Experimental","Exercise","Comparator","No Exercise","Source"," Journal article(s)"]
["Outcome","HRQoL (PC at maximum follow up)","Results","MD = 1.10 (95% CI -9.7, 11.9)","Weight",6.2]
["Domain","Signalling question",null,null,"Response","Comments"]
["Bias arising from the randomization process","1.1 Was the allocation sequence random?",null,null,"Y","The authors state that “patients were randomly allocated 1:1 according to a computer-generated allocation program code”.\r\nAlthough there was no mention of allocation sequence concealment, the fact that they used a computer-generated program code would prevent the enrolling investigator or the participant from having any knowledge of the forthcoming allocation.\r\n"]
[null,"1.2 Was the allocation sequence concealed until participants were enrolled and assigned to interventions?",null,null,"Y"]
[null,"1.3 Did baseline differences between intervention groups suggest a problem with the randomization process?",null,null,"N","No differences for TG and UC with respect to age, proportion of females, The Society of Thoracic Surgeons mortality risk score, NYHA class, prexisting conditions, and medication were observed (see Table I). "]
[null,"Risk of bias judgement",null,null,"Low","The authors state that “patients were randomly allocated 1:1 according to a computer-generated allocation program code”.\r\nAlthough there was no mention of allocation sequence concealment, the fact that they used a computer-generated program code would prevent the enrolling investigator or the participant from having any knowledge of the forthcoming allocation.\r\n\r\nNo differences for TG and UC with respect to age, proportion of females, The Society of Thoracic Surgeons mortality risk score, NYHA class, prexisting conditions, and medication were observed (see Table I). "]
["Bias due to deviations from intended interventions","2.1.Were participants aware of their assigned intervention during the trial?",null,null,"Y","Given the nature of an exercise-based CR intervention, participants are aware of their intervention and it might therefore not be possible to blind them, their carers, or the people delivering this intervention.\r\n"]
[null,"2.2.Were carers and people delivering the interventions aware of participants' assigned intervention during the trial?",null,null,"Y"]
[null,"2.3. If Y/PY/NI to 2.1 or 2.2: Were there deviations from the intended intervention that arose because of the experimental context?",null,null,"N","Although the authors do not specifically state if there were any deviations from the intended intervention, the flow of participants through the study (Fig 1 of 2016 paper) shows that no participant changed groups during the study and all changes to the intervention were either consistent with the intervention (i.e. drop out due to unrelated causes) or consistent with what could occur outside of the trial context (i.e. drop out due to unwillingness to continue participation)."]
[null,"2.4 If Y/PY to 2.3: Were these deviations likely to have affected the outcome?",null,null,"NA"]
[null,"2.5. If Y/PY/NI to 2.4: Were these deviations from intended intervention balanced between groups?",null,null,"NA"]
[null,"2.6 Was an appropriate analysis used to estimate the effect of assignment to intervention?",null,null,"Y","Data were tested for their distribution and the primary end point and key secondary outcomes were normally distributed; thus it was decided to present data as mean (SD). Baseline differences between groups were analyzed using the Student t test for independent samples for continuous variables and the Fisher exact test for categorical variables. Between-group differences in changes of the primary and secondary end points were analyzed using the Student t test for independent samples. For relevant effect sizes (mean differences between study groups), 95% CIs are presented. Because of the low number of dropouts that were all unrelated to the intervention and the primary intention of the study to evaluate efficacy and safety of exercise, a per-protocol analysis was performed. To account for observed differences in baseline parameters between the study groups, linear regression models using the change in the measure of interest as dependent variable and the study group as well as the baseline value of the measure of interest as independent variable were fit to the data. "]
[null,"2.7 If N/PN/NI to 2.6: Was there potential for a substantial impact (on the result) of the failure to analyse participants in the group to which they were randomized?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low","Given the nature of an exercise-based CR intervention, participants are aware of their intervention and it might therefore not be possible to blind them, their carers, or the people delivering this intervention.\r\n\r\nAlthough the authors do not specifically state if there were any deviations from the intended intervention, the flow of participants through the study (Fig 1 of 2016 paper) shows that no participant changed groups during the study and all changes to the intervention were either consistent with the intervention (i.e. drop out due to unrelated causes) or consistent with what could occur outside of the trial context (i.e. drop out due to unwillingness to continue participation).\r\n\r\n\r\nData were tested for their distribution and the primary end point and key secondary outcomes were normally distributed; thus it was decided to present data as mean (SD). Baseline differences between groups were analyzed using the Student t test for independent samples for continuous variables and the Fisher exact test for categorical variables. Between-group differences in changes of the primary and secondary end points were analyzed using the Student t test for independent samples. For relevant effect sizes (mean differences between study groups), 95% CIs are presented. Because of the low number of dropouts that were all unrelated to the intervention and the primary intention of the study to evaluate efficacy and safety of exercise, a per-protocol analysis was performed. To account for observed differences in baseline parameters between the study groups, linear regression models using the change in the measure of interest as dependent variable and the study group as well as the baseline value of the measure of interest as independent variable were fit to the data. \r\n"]
["Bias due to missing outcome data","3.1 Were data for this outcome available for all, or nearly all, participants randomized?",null,null,"N","Considering the fact that the appropriate study population for an analysis of the intention to treat effect is all randomized participants, in this Trial,  less than 95% of the participants in either the exercise group or the control group provided data for this outcome. "]
[null,"3.2 If N/PN/NI to 3.1: Is there evidence that result was not biased by missing outcome data?",null,null,"N","There is no evidence to suggest that the result was not biased by missing outcome data"]
[null,"3.3 If N/PN to 3.2: Could missingness in the outcome depend on its true value?",null,null,"Y","Although reported reasons for missing outcome data are similar between both groups.There is no considerable difference in the proportions of missing outcome data between the two groups overall with 5 patient data missing from the exercise group and 8 patient data missing from the control group. Most of the missing data was due to death or other health conditions not necessarily related to the intervention. The circumstances of the trial do not make it likely that missingness in the outcome depends on its true value as more participants dropped out of the control group than from the exercise group."]
[null,"3.4 If Y/PY/NI to 3.3: Is it likely that missingness in the outcome depended on its true value?",null,null,"PN"]
[null,"Risk of bias judgement",null,null,"Some concerns","Considering the fact that the appropriate study population for an analysis of the intention to treat effect is all randomized participants, in this Trial,  less than 95% of the participants in either the exercise group or the control group provided data for this outcome, as there were 3 overall drop outs. \r\nThere is no evidence to suggest that the result was not biased by missing outcome data\r\nAlthough reported reasons for missing outcome data are similar between both groups.There is no considerable difference in the proportions of missing outcome data between the two groups overall with 5 patient data missing from the exercise group and 8 patient data missing from the control group. Most of the missing data was due to death or other health conditions not necessarily related to the intervention. The circumstances of the trial do not make it likely that missingness in the outcome depends on its true value as more participants dropped out of the control group than from the exercise group.\r\n"]
["Bias in measurement of the outcome","4.1 Was the method of measuring the outcome inappropriate?",null,null,"N","HRQoL measured using SF36 and KCCQ both of which are validated questionnaires"]
[null,"4.2 Could measurement or ascertainment of the outcome have differed between intervention groups?",null,null,"N","Measurements were made in the same way for both intervention and control "]
[null,"4.3 Were outcome assessors aware of the intervention received by study participants?",null,null,"Y","The person reporting this outcome is the participant and they are aware of the intervention received. Collation and analysis of the results were most likely carried out by study personnel who were blinded to the intervention recived by the study participant."]
[null,"4.4 If Y/PY/NI to 4.3: Could assessment of the outcome have been influenced by knowledge of intervention received?",null,null,"Y","\r\nThe assessment by the participants could have been affected by knowledge of the intervention as it is subjective. Exercise is generally believed to be a beneficial intervention in this patient group and it is possible that participants might have considered their HRQoL would be better if they had the intervention."]
[null,"4.5 If Y/PY/NI to 4.4: Is it likely that assessment of the outcome was influenced by knowledge of intervention received?",null,null,"PY"]
[null,"Risk of bias judgement",null,null,"High","HRQoL measured using SF36 and KCCQ both of which are validated questionnaires\r\nMeasurements were made in the same way for both intervention and control \r\nThe person reporting this outcome is the participant and they are aware of the intervention received. Collation and analysis of the results were most likely carried out by study personnel who were blinded to the intervention recived by the study participant.The assessment by the participants could have been affected by knowledge of the intervention as it is subjective. Exercise is generally believed to be a beneficial intervention in this patient group and it is possible that participants might have considered their HRQoL would be better if they had the intervention.\r\n"]
["Bias in selection of the reported result","5.1 Were the data that produced this result analysed in accordance with a pre-specified analysis plan that was finalized before unblinded outcome data were available for analysis?",null,null,"Y","The trial was registered on clinicaltrials.gov before start of the study (NCT01935297) with researchers’ pre-specified intentions available in sufficient detail. There is no reason to believe that the data which produced this result was not analysed in accordance with a pre-specified analysis plan."]
[null,"5.2 ... multiple eligible outcome measurements (e.g. scales, definitions, time points) within the outcome domain?",null,null,"N","The authors provided results for all timepoints at which this outcome was assessed with all extra analysis intended as exploratory analysis to provide additional information on the group-specific impact of the intervention."]
[null,"5.3 ... multiple eligible analyses of the data?",null,null,"N","The authors reported all results. There is therefore no reason to believe that this result might have been selected from multiple eligible analyses of the data."]
[null,"Risk of bias judgement",null,null,"Low","The trial was registered on clinicaltrials.gov before start of the study (NCT01935297) with researchers’ pre-specified intentions available in sufficient detail. There is no reason to believe that the data which produced this result was not analysed in accordance with a pre-specified analysis plan.\r\nThe authors provided results for all timepoints at which this outcome was assessed with all extra analysis intended as exploratory analysis to provide additional information on the group-specific impact of the intervention.\r\nThe authors reported all results. There is therefore no reason to believe that this result might have been selected from multiple eligible analyses of the data."]
["Overall bias","Risk of bias judgement",null,null,"High","The authors state that “patients were randomly allocated 1:1 according to a computer-generated allocation program code”.\r\nAlthough there was no mention of allocation sequence concealment, the fact that they used a computer-generated program code would prevent the enrolling investigator or the participant from having any knowledge of the forthcoming allocation.\r\n\r\nNo differences for TG and UC with respect to age, proportion of females, The Society of Thoracic Surgeons mortality risk score, NYHA class, prexisting conditions, and medication were observed (see Table I). \r\nGiven the nature of an exercise-based CR intervention, participants are aware of their intervention and it might therefore not be possible to blind them, their carers, or the people delivering this intervention.\r\n\r\nAlthough the authors do not specifically state if there were any deviations from the intended intervention, the flow of participants through the study (Fig 1 of 2016 paper) shows that no participant changed groups during the study and all changes to the intervention were either consistent with the intervention (i.e. drop out due to unrelated causes) or consistent with what could occur outside of the trial context (i.e. drop out due to unwillingness to continue participation).\r\n\r\n\r\nData were tested for their distribution and the primary end point and key secondary outcomes were normally distributed; thus it was decided to present data as mean (SD). Baseline differences between groups were analyzed using the Student t test for independent samples for continuous variables and the Fisher exact test for categorical variables. Between-group differences in changes of the primary and secondary end points were analyzed using the Student t test for independent samples. For relevant effect sizes (mean differences between study groups), 95% CIs are presented. Because of the low number of dropouts that were all unrelated to the intervention and the primary intention of the study to evaluate efficacy and safety of exercise, a per-protocol analysis was performed. To account for observed differences in baseline parameters between the study groups, linear regression models using the change in the measure of interest as dependent variable and the study group as well as the baseline value of the measure of interest as independent variable were fit to the data. \r\n\r\nConsidering the fact that the appropriate study population for an analysis of the intention to treat effect is all randomized participants, in this Trial,  less than 95% of the participants in either the exercise group or the control group provided data for this outcome, as there were 3 overall drop outs. \r\nThere is no evidence to suggest that the result was not biased by missing outcome data\r\nAlthough reported reasons for missing outcome data are similar between both groups.There is no considerable difference in the proportions of missing outcome data between the two groups overall with 5 patient data missing from the exercise group and 8 patient data missing from the control group. Most of the missing data was due to death or other health conditions not necessarily related to the intervention. The circumstances of the trial do not make it likely that missingness in the outcome depends on its true value as more participants dropped out of the control group than from the exercise group.\r\n\r\nHRQoL measured using SF36 and KCCQ both of which are validated questionnaires\r\nMeasurements were made in the same way for both intervention and control \r\nThe person reporting this outcome is the participant and they are aware of the intervention received. Collation and analysis of the results were most likely carried out by study personnel who were blinded to the intervention recived by the study participant.The assessment by the participants could have been affected by knowledge of the intervention as it is subjective. Exercise is generally believed to be a beneficial intervention in this patient group and it is possible that participants might have considered their HRQoL would be better if they had the intervention.\r\n\r\nThe trial was registered on clinicaltrials.gov before start of the study (NCT01935297) with researchers’ pre-specified intentions available in sufficient detail. There is no reason to believe that the data which produced this result was not analysed in accordance with a pre-specified analysis plan.\r\nThe authors provided results for all timepoints at which this outcome was assessed with all extra analysis intended as exploratory analysis to provide additional information on the group-specific impact of the intervention.\r\nThe authors reported all results. There is therefore no reason to believe that this result might have been selected from multiple eligible analyses of the data."]
[]
[]
["Unique ID","4_A","Study ID","Sibilitz 2016","Assessor","MHB"]
["Ref or Label","Heart 2016; 102; 1995-2003","Aim","assignment to intervention (the 'intention-to-treat' effect)\n\n"]
["Experimental","Exercise","Comparator","No Exercise","Source"," Journal article(s); Trial protocol"]
["Outcome","All-Cause Hospitalisation","Results","RR = 2.72 (95% CI 0.11, 65.56)","Weight",100]
["Domain","Signalling question",null,null,"Response","Comments"]
["Bias arising from the randomization process","1.1 Was the allocation sequence random?",null,null,"Y","Patients were allocated to intervention or control using computer-generated allocation sequence with varying block sizes of 8, 6, or 4, concealed to the investigators by central telephone correspondence with the Copenhagen Trial Unit."]
[null,"1.2 Was the allocation sequence concealed until participants were enrolled and assigned to interventions?",null,null,"Y"]
[null,"1.3 Did baseline differences between intervention groups suggest a problem with the randomization process?",null,null,"N","see table 1"]
[null,"Risk of bias judgement",null,null,"Low","Patients were allocated to intervention or control using computer-generated allocation sequence with varying block sizes of 8, 6, or 4, concealed to the investigators by central telephone correspondence with the Copenhagen Trial Unit.\r\nsee table 1"]
["Bias due to deviations from intended interventions","2.1.Were participants aware of their assigned intervention during the trial?",null,null,"Y","\"Blinding of clinicians and participants is impossible in a rehabilitation trial.\""]
[null,"2.2.Were carers and people delivering the interventions aware of participants' assigned intervention during the trial?",null,null,"Y"]
[null,"2.3. If Y/PY/NI to 2.1 or 2.2: Were there deviations from the intended intervention that arose because of the experimental context?",null,null,"PN","\"A major concern is that the control group might have received different interventions at the local hospitals, which might diminish the impact of our experimental intervention.\" p. 2002"]
[null,"2.4 If Y/PY to 2.3: Were these deviations likely to have affected the outcome?",null,null,"NA"]
[null,"2.5. If Y/PY/NI to 2.4: Were these deviations from intended intervention balanced between groups?",null,null,"NA"]
[null,"2.6 Was an appropriate analysis used to estimate the effect of assignment to intervention?",null,null,"PY","Count data only; just one event observed"]
[null,"2.7 If N/PN/NI to 2.6: Was there potential for a substantial impact (on the result) of the failure to analyse participants in the group to which they were randomized?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low","\"Blinding of clinicians and participants is impossible in a rehabilitation trial.\"\r\n\"A major concern is that the control group might have received different interventions at the local hospitals, which might diminish the impact of our experimental intervention.\" p. 2002\r\n\r\n\r\nCount data only; just one event observed\r\n"]
["Bias due to missing outcome data","3.1 Were data for this outcome available for all, or nearly all, participants randomized?",null,null,"NI","There is no information as to whether all-cause hospitalisation data were sought for all participants"]
[null,"3.2 If N/PN/NI to 3.1: Is there evidence that result was not biased by missing outcome data?",null,null,"PN","1 rehospitalisation out of 147 heart valve surgery patients over six months seems very low. "]
[null,"3.3 If N/PN to 3.2: Could missingness in the outcome depend on its true value?",null,null,"PY","\"dropouts were due to complications after surgery\" which may well have involved rehospitalisation"]
[null,"3.4 If Y/PY/NI to 3.3: Is it likely that missingness in the outcome depended on its true value?",null,null,"PY"]
[null,"Risk of bias judgement",null,null,"High","There is no information as to whether all-cause hospitalisation data were sought for all participants\r\n1 rehospitalisation out of 147 heart valve surgery patients over six months seems very low. \r\n\"dropouts were due to complications after surgery\" which may well have involved rehospitalisation\r\n"]
["Bias in measurement of the outcome","4.1 Was the method of measuring the outcome inappropriate?",null,null,"PY","Reporting adverse events is probably a substantially different and less comprehensive measurement method compared to other methods of measuring all-cause hospitalisation"]
[null,"4.2 Could measurement or ascertainment of the outcome have differed between intervention groups?",null,null,"PN","It is possible but unlikely that adverse events could have been investigated differently in the intervention group because assignment was not blinded"]
[null,"4.3 Were outcome assessors aware of the intervention received by study participants?",null,null,"NA"]
[null,"4.4 If Y/PY/NI to 4.3: Could assessment of the outcome have been influenced by knowledge of intervention received?",null,null,"NA"]
[null,"4.5 If Y/PY/NI to 4.4: Is it likely that assessment of the outcome was influenced by knowledge of intervention received?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"High","Reporting adverse events is probably a substantially different and less comprehensive measurement method compared to other methods of measuring all-cause hospitalisation\r\nIt is possible but unlikely that adverse events could have been investigated differently in the intervention group because assignment was not blinded\r\n\r\n\r\n"]
["Bias in selection of the reported result","5.1 Were the data that produced this result analysed in accordance with a pre-specified analysis plan that was finalized before unblinded outcome data were available for analysis?",null,null,"N","The protocol does not specify all-cause hospitalisation as a primary or secondary outcome, and does not state how adverse events will be defined or analysed."]
[null,"5.2 ... multiple eligible outcome measurements (e.g. scales, definitions, time points) within the outcome domain?",null,null,"PN","All-cause hospitalisation was not mentioned as an outcome in the study protocol and definitions of adverse events were not provided"]
[null,"5.3 ... multiple eligible analyses of the data?",null,null,"PN","only one event was observed"]
[null,"Risk of bias judgement",null,null,"Some concerns","The protocol does not specify all-cause hospitalisation as a primary or secondary outcome, and does not state how adverse events will be defined or analysed.\r\nAll-cause hospitalisation was not mentioned as an outcome in the study protocol and definitions of adverse events were not provided\r\nonly one event was observed"]
["Overall bias","Risk of bias judgement",null,null,"High","Patients were allocated to intervention or control using computer-generated allocation sequence with varying block sizes of 8, 6, or 4, concealed to the investigators by central telephone correspondence with the Copenhagen Trial Unit.\r\nsee table 1\r\n\"Blinding of clinicians and participants is impossible in a rehabilitation trial.\"\r\n\"A major concern is that the control group might have received different interventions at the local hospitals, which might diminish the impact of our experimental intervention.\" p. 2002\r\n\r\n\r\nCount data only; just one event observed\r\n\r\nThere is no information as to whether all-cause hospitalisation data were sought for all participants\r\n1 rehospitalisation out of 147 heart valve surgery patients over six months seems very low. \r\n\"dropouts were due to complications after surgery\" which may well have involved rehospitalisation\r\n\r\nReporting adverse events is probably a substantially different and less comprehensive measurement method compared to other methods of measuring all-cause hospitalisation\r\nIt is possible but unlikely that adverse events could have been investigated differently in the intervention group because assignment was not blinded\r\n\r\n\r\n\r\nThe protocol does not specify all-cause hospitalisation as a primary or secondary outcome, and does not state how adverse events will be defined or analysed.\r\nAll-cause hospitalisation was not mentioned as an outcome in the study protocol and definitions of adverse events were not provided\r\nonly one event was observed"]
[]
[]
["Unique ID","4_B","Study ID","Sibilitz 2016","Assessor","MHB"]
["Ref or Label","Heart 2016; 102: 1995-2003","Aim","assignment to intervention (the 'intention-to-treat' effect)\n\n"]
["Experimental","Exercise","Comparator","No Exercise","Source"," Journal article(s); Trial protocol"]
["Outcome","HRQoL (MC End of Intervention)","Results","MD = 0.8 (95% CI -2.46, 4.06)","Weight",78.2]
["Domain","Signalling question",null,null,"Response","Comments"]
["Bias arising from the randomization process","1.1 Was the allocation sequence random?",null,null,"Y","Patients were allocated to intervention or control using computer-generated allocation sequence with varying block sizes of 8, 6, or 4, concealed to the investigators by central telephone correspondence with the Copenhagen Trial Unit."]
[null,"1.2 Was the allocation sequence concealed until participants were enrolled and assigned to interventions?",null,null,"Y"]
[null,"1.3 Did baseline differences between intervention groups suggest a problem with the randomization process?",null,null,"N","see Table 1"]
[null,"Risk of bias judgement",null,null,"Low","Patients were allocated to intervention or control using computer-generated allocation sequence with varying block sizes of 8, 6, or 4, concealed to the investigators by central telephone correspondence with the Copenhagen Trial Unit.\r\nsee Table 1"]
["Bias due to deviations from intended interventions","2.1.Were participants aware of their assigned intervention during the trial?",null,null,"Y","\"Blinding of clinicians and participants is impossible in a rehabilitation trial.\""]
[null,"2.2.Were carers and people delivering the interventions aware of participants' assigned intervention during the trial?",null,null,"Y"]
[null,"2.3. If Y/PY/NI to 2.1 or 2.2: Were there deviations from the intended intervention that arose because of the experimental context?",null,null,"PN","\"A major concern is that the control group might have received different interventions at the local hospitals, which might diminish the impact of our experimental intervention.\" p. 2002"]
[null,"2.4 If Y/PY to 2.3: Were these deviations likely to have affected the outcome?",null,null,"NA"]
[null,"2.5. If Y/PY/NI to 2.4: Were these deviations from intended intervention balanced between groups?",null,null,"NA"]
[null,"2.6 Was an appropriate analysis used to estimate the effect of assignment to intervention?",null,null,"Y","The analysis was based on intention to treat using a mixed model with repeated measures (MMRM) and adjusted for the stratification variable"]
[null,"2.7 If N/PN/NI to 2.6: Was there potential for a substantial impact (on the result) of the failure to analyse participants in the group to which they were randomized?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low","\"Blinding of clinicians and participants is impossible in a rehabilitation trial.\"\r\n\"A major concern is that the control group might have received different interventions at the local hospitals, which might diminish the impact of our experimental intervention.\" p. 2002\r\n\r\n\r\nThe analysis was based on intention to treat using a mixed model with repeated measures (MMRM) and adjusted for the stratification variable\r\n"]
["Bias due to missing outcome data","3.1 Were data for this outcome available for all, or nearly all, participants randomized?",null,null,"Y","Data available for this outcome for 65/72 intervention and 61/75 control group"]
[null,"3.2 If N/PN/NI to 3.1: Is there evidence that result was not biased by missing outcome data?",null,null,"NA"]
[null,"3.3 If N/PN to 3.2: Could missingness in the outcome depend on its true value?",null,null,"NA"]
[null,"3.4 If Y/PY/NI to 3.3: Is it likely that missingness in the outcome depended on its true value?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low","Data available for this outcome for 65/72 intervention and 61/75 control group\r\n\r\n\r\n"]
["Bias in measurement of the outcome","4.1 Was the method of measuring the outcome inappropriate?",null,null,"N","mental health was measured by SF-36, Mental Component Scale"]
[null,"4.2 Could measurement or ascertainment of the outcome have differed between intervention groups?",null,null,"PN","same validated scale used in both groups"]
[null,"4.3 Were outcome assessors aware of the intervention received by study participants?",null,null,"Y","self-reported by participants aware of their allocation"]
[null,"4.4 If Y/PY/NI to 4.3: Could assessment of the outcome have been influenced by knowledge of intervention received?",null,null,"PY","possible, but unlikely as there was no difference between groups"]
[null,"4.5 If Y/PY/NI to 4.4: Is it likely that assessment of the outcome was influenced by knowledge of intervention received?",null,null,"PN"]
[null,"Risk of bias judgement",null,null,"Some concerns","mental health was measured by SF-36, Mental Component Scale\r\nsame validated scale used in both groups\r\nself-reported by participants aware of their allocation\r\npossible, but unlikely as there was no difference between groups\r\n"]
["Bias in selection of the reported result","5.1 Were the data that produced this result analysed in accordance with a pre-specified analysis plan that was finalized before unblinded outcome data were available for analysis?",null,null,"PY","The analysis seems in accordance with the analysis implied by the protocol, although a detailed pre-specified analysis plan was not identified."]
[null,"5.2 ... multiple eligible outcome measurements (e.g. scales, definitions, time points) within the outcome domain?",null,null,"PN","The outcome measurements in the report were specified in the protocol and results are reported for all time points recorded."]
[null,"5.3 ... multiple eligible analyses of the data?",null,null,"PN","\"No interaction between intervention and time was observedfor SF-36 MCSbetween groups at 6 months\""]
[null,"Risk of bias judgement",null,null,"Low","The analysis seems in accordance with the analysis implied by the protocol, although a detailed pre-specified analysis plan was not identified.\r\nThe outcome measurements in the report were specified in the protocol and results are reported for all time points recorded.\r\n\"No interaction between intervention and time was observedfor SF-36 MCSbetween groups at 6 months\""]
["Overall bias","Risk of bias judgement",null,null,"Some concerns","Patients were allocated to intervention or control using computer-generated allocation sequence with varying block sizes of 8, 6, or 4, concealed to the investigators by central telephone correspondence with the Copenhagen Trial Unit.\r\nsee Table 1\r\n\"Blinding of clinicians and participants is impossible in a rehabilitation trial.\"\r\n\"A major concern is that the control group might have received different interventions at the local hospitals, which might diminish the impact of our experimental intervention.\" p. 2002\r\n\r\n\r\nThe analysis was based on intention to treat using a mixed model with repeated measures (MMRM) and adjusted for the stratification variable\r\n\r\nData available for this outcome for 65/72 intervention and 61/75 control group\r\n\r\n\r\n\r\nmental health was measured by SF-36, Mental Component Scale\r\nsame validated scale used in both groups\r\nself-reported by participants aware of their allocation\r\npossible, but unlikely as there was no difference between groups\r\n\r\nThe analysis seems in accordance with the analysis implied by the protocol, although a detailed pre-specified analysis plan was not identified.\r\nThe outcome measurements in the report were specified in the protocol and results are reported for all time points recorded.\r\n\"No interaction between intervention and time was observedfor SF-36 MCSbetween groups at 6 months\""]
[]
[]
["Unique ID","4_C","Study ID","Sibilitz 2016","Assessor","MHB"]
["Ref or Label","Heart 2016; 102: 1995-2003","Aim","assignment to intervention (the 'intention-to-treat' effect)\n\n"]
["Experimental","Exercise","Comparator","No Exercise","Source"," Journal article(s); Trial protocol"]
["Outcome","HRQoL (PC End of Intervention)","Results","MD = -0.6 (95% CI -3.43, 2.23)","Weight",57.8]
["Domain","Signalling question",null,null,"Response","Comments"]
["Bias arising from the randomization process","1.1 Was the allocation sequence random?",null,null,"Y","Patients were allocated to intervention or control using computer-generated allocation sequence with varying block sizes of 8, 6, or 4, concealed to the investigators by central telephone correspondence with the Copenhagen Trial Unit."]
[null,"1.2 Was the allocation sequence concealed until participants were enrolled and assigned to interventions?",null,null,"Y"]
[null,"1.3 Did baseline differences between intervention groups suggest a problem with the randomization process?",null,null,"N","see Table 1"]
[null,"Risk of bias judgement",null,null,"Low","Patients were allocated to intervention or control using computer-generated allocation sequence with varying block sizes of 8, 6, or 4, concealed to the investigators by central telephone correspondence with the Copenhagen Trial Unit.\r\nsee Table 1"]
["Bias due to deviations from intended interventions","2.1.Were participants aware of their assigned intervention during the trial?",null,null,"Y","\"Blinding of clinicians and participants is impossible in a rehabilitation trial.\""]
[null,"2.2.Were carers and people delivering the interventions aware of participants' assigned intervention during the trial?",null,null,"Y"]
[null,"2.3. If Y/PY/NI to 2.1 or 2.2: Were there deviations from the intended intervention that arose because of the experimental context?",null,null,"PN","\"A major concern is that the control group might have received different interventions at the local hospitals, which might diminish the impact of our experimental intervention.\" p. 2003"]
[null,"2.4 If Y/PY to 2.3: Were these deviations likely to have affected the outcome?",null,null,"NA"]
[null,"2.5. If Y/PY/NI to 2.4: Were these deviations from intended intervention balanced between groups?",null,null,"NA"]
[null,"2.6 Was an appropriate analysis used to estimate the effect of assignment to intervention?",null,null,"Y","The analysis was based on intention to treat using a mixed model with repeated measures (MMRM) and adjusted for the stratification variable"]
[null,"2.7 If N/PN/NI to 2.6: Was there potential for a substantial impact (on the result) of the failure to analyse participants in the group to which they were randomized?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low","\"Blinding of clinicians and participants is impossible in a rehabilitation trial.\"\r\n\"A major concern is that the control group might have received different interventions at the local hospitals, which might diminish the impact of our experimental intervention.\" p. 2003\r\n\r\n\r\nThe analysis was based on intention to treat using a mixed model with repeated measures (MMRM) and adjusted for the stratification variable\r\n"]
["Bias due to missing outcome data","3.1 Were data for this outcome available for all, or nearly all, participants randomized?",null,null,"Y","Data were available for 65/72 treated and 61/75 controls for this outcome"]
[null,"3.2 If N/PN/NI to 3.1: Is there evidence that result was not biased by missing outcome data?",null,null,"NA"]
[null,"3.3 If N/PN to 3.2: Could missingness in the outcome depend on its true value?",null,null,"NA"]
[null,"3.4 If Y/PY/NI to 3.3: Is it likely that missingness in the outcome depended on its true value?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low","Data were available for 65/72 treated and 61/75 controls for this outcome\r\n\r\n\r\n"]
["Bias in measurement of the outcome","4.1 Was the method of measuring the outcome inappropriate?",null,null,"N","Physical HRQoL was measured with the Physical Component Scale of SF-36"]
[null,"4.2 Could measurement or ascertainment of the outcome have differed between intervention groups?",null,null,"PN","same validated scale used in both groups"]
[null,"4.3 Were outcome assessors aware of the intervention received by study participants?",null,null,"Y","self-reported by participants aware of their allocation"]
[null,"4.4 If Y/PY/NI to 4.3: Could assessment of the outcome have been influenced by knowledge of intervention received?",null,null,"PY","possible, but unlikely as there was no difference between groups"]
[null,"4.5 If Y/PY/NI to 4.4: Is it likely that assessment of the outcome was influenced by knowledge of intervention received?",null,null,"PN"]
[null,"Risk of bias judgement",null,null,"Some concerns","Physical HRQoL was measured with the Physical Component Scale of SF-36\r\nsame validated scale used in both groups\r\nself-reported by participants aware of their allocation\r\npossible, but unlikely as there was no difference between groups\r\n"]
["Bias in selection of the reported result","5.1 Were the data that produced this result analysed in accordance with a pre-specified analysis plan that was finalized before unblinded outcome data were available for analysis?",null,null,"PY","The analysis seems in accordance with the analysis implied by the protocol, although a detailed pre-specified analysis plan was not identified and this particular component of SF-36 was not mentioned in the protocol."]
[null,"5.2 ... multiple eligible outcome measurements (e.g. scales, definitions, time points) within the outcome domain?",null,null,"PN","The outcome measurements are reported for 1, 4, and 6 months follow up."]
[null,"5.3 ... multiple eligible analyses of the data?",null,null,"PN","There is no statistically significant difference between groups in the reported outcome."]
[null,"Risk of bias judgement",null,null,"Low","The analysis seems in accordance with the analysis implied by the protocol, although a detailed pre-specified analysis plan was not identified and this particular component of SF-36 was not mentioned in the protocol.\r\nThe outcome measurements are reported for 1, 4, and 6 months follow up.\r\nThere is no statistically significant difference between groups in the reported outcome."]
["Overall bias","Risk of bias judgement",null,null,"Some concerns","Patients were allocated to intervention or control using computer-generated allocation sequence with varying block sizes of 8, 6, or 4, concealed to the investigators by central telephone correspondence with the Copenhagen Trial Unit.\r\nsee Table 1\r\n\"Blinding of clinicians and participants is impossible in a rehabilitation trial.\"\r\n\"A major concern is that the control group might have received different interventions at the local hospitals, which might diminish the impact of our experimental intervention.\" p. 2003\r\n\r\n\r\nThe analysis was based on intention to treat using a mixed model with repeated measures (MMRM) and adjusted for the stratification variable\r\n\r\nData were available for 65/72 treated and 61/75 controls for this outcome\r\n\r\n\r\n\r\nPhysical HRQoL was measured with the Physical Component Scale of SF-36\r\nsame validated scale used in both groups\r\nself-reported by participants aware of their allocation\r\npossible, but unlikely as there was no difference between groups\r\n\r\nThe analysis seems in accordance with the analysis implied by the protocol, although a detailed pre-specified analysis plan was not identified and this particular component of SF-36 was not mentioned in the protocol.\r\nThe outcome measurements are reported for 1, 4, and 6 months follow up.\r\nThere is no statistically significant difference between groups in the reported outcome."]
[]
[]
["Unique ID","4_D","Study ID","Sibilitz 2016","Assessor","MHB"]
["Ref or Label","Heart 2016; 102: 1995-2003","Aim","assignment to intervention (the 'intention-to-treat' effect)\n\n"]
["Experimental","Exercise","Comparator","No Exercise","Source"," Journal article(s); Trial protocol"]
["Outcome","HRQoL (MC Maximum Follow-up)","Results","MD = -1.5 (95% CI -4.93, 1.93)","Weight",90]
["Domain","Signalling question",null,null,"Response","Comments"]
["Bias arising from the randomization process","1.1 Was the allocation sequence random?",null,null,"Y","Patients were allocated to intervention or control using computer-generated allocation sequence with varying block sizes of 8, 6, or 4, concealed to the investigators by central telephone correspondence with the Copenhagen Trial Unit."]
[null,"1.2 Was the allocation sequence concealed until participants were enrolled and assigned to interventions?",null,null,"Y"]
[null,"1.3 Did baseline differences between intervention groups suggest a problem with the randomization process?",null,null,"N","see Table 1"]
[null,"Risk of bias judgement",null,null,"Low","Patients were allocated to intervention or control using computer-generated allocation sequence with varying block sizes of 8, 6, or 4, concealed to the investigators by central telephone correspondence with the Copenhagen Trial Unit.\r\nsee Table 1"]
["Bias due to deviations from intended interventions","2.1.Were participants aware of their assigned intervention during the trial?",null,null,"Y","\"Blinding of clinicians and participants is impossible in a rehabilitation trial.\""]
[null,"2.2.Were carers and people delivering the interventions aware of participants' assigned intervention during the trial?",null,null,"Y"]
[null,"2.3. If Y/PY/NI to 2.1 or 2.2: Were there deviations from the intended intervention that arose because of the experimental context?",null,null,"PN","\"A major concern is that the control group might have received different interventions at the local hospitals, which might diminish the impact of our experimental intervention.\" p. 2004"]
[null,"2.4 If Y/PY to 2.3: Were these deviations likely to have affected the outcome?",null,null,"NA"]
[null,"2.5. If Y/PY/NI to 2.4: Were these deviations from intended intervention balanced between groups?",null,null,"NA"]
[null,"2.6 Was an appropriate analysis used to estimate the effect of assignment to intervention?",null,null,"Y","\"The analysis was based on intention to treat using a mixed model with repeated measures (MMRM) and adjusted for the stratification variable\""]
[null,"2.7 If N/PN/NI to 2.6: Was there potential for a substantial impact (on the result) of the failure to analyse participants in the group to which they were randomized?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low","\"Blinding of clinicians and participants is impossible in a rehabilitation trial.\"\r\n\"A major concern is that the control group might have received different interventions at the local hospitals, which might diminish the impact of our experimental intervention.\" p. 2004\r\n\r\n\r\n\"The analysis was based on intention to treat using a mixed model with repeated measures (MMRM) and adjusted for the stratification variable\"\r\n"]
["Bias due to missing outcome data","3.1 Were data for this outcome available for all, or nearly all, participants randomized?",null,null,"PY","at 6 months data were available for 64/72 treated and 58/75 control, which seems reasonable for this type of intervention and length of follow up"]
[null,"3.2 If N/PN/NI to 3.1: Is there evidence that result was not biased by missing outcome data?",null,null,"NA"]
[null,"3.3 If N/PN to 3.2: Could missingness in the outcome depend on its true value?",null,null,"NA"]
[null,"3.4 If Y/PY/NI to 3.3: Is it likely that missingness in the outcome depended on its true value?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low","at 6 months data were available for 64/72 treated and 58/75 control, which seems reasonable for this type of intervention and length of follow up\r\n\r\n\r\n"]
["Bias in measurement of the outcome","4.1 Was the method of measuring the outcome inappropriate?",null,null,"N","mental health was measured by SF-36, Mental Component Scale"]
[null,"4.2 Could measurement or ascertainment of the outcome have differed between intervention groups?",null,null,"PN","same validated scale used in both groups"]
[null,"4.3 Were outcome assessors aware of the intervention received by study participants?",null,null,"Y","self-reported by participants aware of their allocation"]
[null,"4.4 If Y/PY/NI to 4.3: Could assessment of the outcome have been influenced by knowledge of intervention received?",null,null,"PY","possible, but unlikely as there was no difference between groups"]
[null,"4.5 If Y/PY/NI to 4.4: Is it likely that assessment of the outcome was influenced by knowledge of intervention received?",null,null,"PN"]
[null,"Risk of bias judgement",null,null,"Some concerns","mental health was measured by SF-36, Mental Component Scale\r\nsame validated scale used in both groups\r\nself-reported by participants aware of their allocation\r\npossible, but unlikely as there was no difference between groups\r\n"]
["Bias in selection of the reported result","5.1 Were the data that produced this result analysed in accordance with a pre-specified analysis plan that was finalized before unblinded outcome data were available for analysis?",null,null,"PY","The analysis seems in accordance with the analysis implied by the protocol, although a detailed pre-specified analysis plan was not identified."]
[null,"5.2 ... multiple eligible outcome measurements (e.g. scales, definitions, time points) within the outcome domain?",null,null,"PN","The outcome measurements in the report were specified in the protocol and results are reported for all time points recorded."]
[null,"5.3 ... multiple eligible analyses of the data?",null,null,"PN","There is no statistically significant difference between groups in the reported outcome."]
[null,"Risk of bias judgement",null,null,"Low","The analysis seems in accordance with the analysis implied by the protocol, although a detailed pre-specified analysis plan was not identified.\r\nThe outcome measurements in the report were specified in the protocol and results are reported for all time points recorded.\r\nThere is no statistically significant difference between groups in the reported outcome."]
["Overall bias","Risk of bias judgement",null,null,"Some concerns","Patients were allocated to intervention or control using computer-generated allocation sequence with varying block sizes of 8, 6, or 4, concealed to the investigators by central telephone correspondence with the Copenhagen Trial Unit.\r\nsee Table 1\r\n\"Blinding of clinicians and participants is impossible in a rehabilitation trial.\"\r\n\"A major concern is that the control group might have received different interventions at the local hospitals, which might diminish the impact of our experimental intervention.\" p. 2004\r\n\r\n\r\n\"The analysis was based on intention to treat using a mixed model with repeated measures (MMRM) and adjusted for the stratification variable\"\r\n\r\nat 6 months data were available for 64/72 treated and 58/75 control, which seems reasonable for this type of intervention and length of follow up\r\n\r\n\r\n\r\nmental health was measured by SF-36, Mental Component Scale\r\nsame validated scale used in both groups\r\nself-reported by participants aware of their allocation\r\npossible, but unlikely as there was no difference between groups\r\n\r\nThe analysis seems in accordance with the analysis implied by the protocol, although a detailed pre-specified analysis plan was not identified.\r\nThe outcome measurements in the report were specified in the protocol and results are reported for all time points recorded.\r\nThere is no statistically significant difference between groups in the reported outcome."]
[]
[]
["Unique ID","4_E","Study ID","Sibilitz 2016","Assessor","MHB"]
["Ref or Label","Heart 2016; 102: 1995-2003","Aim","assignment to intervention (the 'intention-to-treat' effect)\n\n"]
["Experimental","Exercise","Comparator","No Exercise","Source"," Journal article(s); Trial protocol"]
["Outcome","HRQoL (PC Maximum Follow-up)","Results","MD = -1 (95% CI -3.79, 1.79)","Weight",93.8]
["Domain","Signalling question",null,null,"Response","Comments"]
["Bias arising from the randomization process","1.1 Was the allocation sequence random?",null,null,"Y","Patients were allocated to intervention or control using computer-generated allocation sequence with varying block sizes of 8, 6, or 4, concealed to the investigators by central telephone correspondence with the Copenhagen Trial Unit."]
[null,"1.2 Was the allocation sequence concealed until participants were enrolled and assigned to interventions?",null,null,"Y"]
[null,"1.3 Did baseline differences between intervention groups suggest a problem with the randomization process?",null,null,"N","see Table 1"]
[null,"Risk of bias judgement",null,null,"Low","Patients were allocated to intervention or control using computer-generated allocation sequence with varying block sizes of 8, 6, or 4, concealed to the investigators by central telephone correspondence with the Copenhagen Trial Unit.\r\nsee Table 1"]
["Bias due to deviations from intended interventions","2.1.Were participants aware of their assigned intervention during the trial?",null,null,"Y","\"Blinding of clinicians and participants is impossible in a rehabilitation trial.\""]
[null,"2.2.Were carers and people delivering the interventions aware of participants' assigned intervention during the trial?",null,null,"Y"]
[null,"2.3. If Y/PY/NI to 2.1 or 2.2: Were there deviations from the intended intervention that arose because of the experimental context?",null,null,"PN","\"A major concern is that the control group might have received different interventions at the local hospitals, which might diminish the impact of our experimental intervention.\" p. 2005"]
[null,"2.4 If Y/PY to 2.3: Were these deviations likely to have affected the outcome?",null,null,"NA"]
[null,"2.5. If Y/PY/NI to 2.4: Were these deviations from intended intervention balanced between groups?",null,null,"NA"]
[null,"2.6 Was an appropriate analysis used to estimate the effect of assignment to intervention?",null,null,"Y","The analysis was based on intention to treat using a mixed model with repeated measures (MMRM) and adjusted for the stratification variable"]
[null,"2.7 If N/PN/NI to 2.6: Was there potential for a substantial impact (on the result) of the failure to analyse participants in the group to which they were randomized?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low","\"Blinding of clinicians and participants is impossible in a rehabilitation trial.\"\r\n\"A major concern is that the control group might have received different interventions at the local hospitals, which might diminish the impact of our experimental intervention.\" p. 2005\r\n\r\n\r\nThe analysis was based on intention to treat using a mixed model with repeated measures (MMRM) and adjusted for the stratification variable\r\n"]
["Bias due to missing outcome data","3.1 Were data for this outcome available for all, or nearly all, participants randomized?",null,null,"Y","Data were available for 64/72 treated and 58/75 control, which seems reasonable for this type of intervention"]
[null,"3.2 If N/PN/NI to 3.1: Is there evidence that result was not biased by missing outcome data?",null,null,"NA"]
[null,"3.3 If N/PN to 3.2: Could missingness in the outcome depend on its true value?",null,null,"NA"]
[null,"3.4 If Y/PY/NI to 3.3: Is it likely that missingness in the outcome depended on its true value?",null,null,"NA"]
[null,"Risk of bias judgement",null,null,"Low","Data were available for 64/72 treated and 58/75 control, which seems reasonable for this type of intervention\r\n\r\n\r\n"]
["Bias in measurement of the outcome","4.1 Was the method of measuring the outcome inappropriate?",null,null,"N","Physical HRQoL was measured with the Physical Component Scale of SF-36"]
[null,"4.2 Could measurement or ascertainment of the outcome have differed between intervention groups?",null,null,"PN","same validated scale used in both groups"]
[null,"4.3 Were outcome assessors aware of the intervention received by study participants?",null,null,"Y","self-reported by participants aware of their allocation"]
[null,"4.4 If Y/PY/NI to 4.3: Could assessment of the outcome have been influenced by knowledge of intervention received?",null,null,"PY","possible, but unlikely as there was no difference between groups"]
[null,"4.5 If Y/PY/NI to 4.4: Is it likely that assessment of the outcome was influenced by knowledge of intervention received?",null,null,"PN"]
[null,"Risk of bias judgement",null,null,"Some concerns","Physical HRQoL was measured with the Physical Component Scale of SF-36\r\nsame validated scale used in both groups\r\nself-reported by participants aware of their allocation\r\npossible, but unlikely as there was no difference between groups\r\n"]
["Bias in selection of the reported result","5.1 Were the data that produced this result analysed in accordance with a pre-specified analysis plan that was finalized before unblinded outcome data were available for analysis?",null,null,"PY","The analysis seems in accordance with the analysis implied by the protocol, although a detailed pre-specified analysis plan was not identified and this particular component of SF-36 was not mentioned in the protocol."]
[null,"5.2 ... multiple eligible outcome measurements (e.g. scales, definitions, time points) within the outcome domain?",null,null,"PN","results are reported for all time points recorded."]
[null,"5.3 ... multiple eligible analyses of the data?",null,null,"PN","There is no statistically significant difference between groups in the reported outcome."]
[null,"Risk of bias judgement",null,null,"Low","The analysis seems in accordance with the analysis implied by the protocol, although a detailed pre-specified analysis plan was not identified and this particular component of SF-36 was not mentioned in the protocol.\r\nresults are reported for all time points recorded.\r\nThere is no statistically significant difference between groups in the reported outcome."]
["Overall bias","Risk of bias judgement",null,null,"Some concerns","Patients were allocated to intervention or control using computer-generated allocation sequence with varying block sizes of 8, 6, or 4, concealed to the investigators by central telephone correspondence with the Copenhagen Trial Unit.\r\nsee Table 1\r\n\"Blinding of clinicians and participants is impossible in a rehabilitation trial.\"\r\n\"A major concern is that the control group might have received different interventions at the local hospitals, which might diminish the impact of our experimental intervention.\" p. 2005\r\n\r\n\r\nThe analysis was based on intention to treat using a mixed model with repeated measures (MMRM) and adjusted for the stratification variable\r\n\r\nData were available for 64/72 treated and 58/75 control, which seems reasonable for this type of intervention\r\n\r\n\r\n\r\nPhysical HRQoL was measured with the Physical Component Scale of SF-36\r\nsame validated scale used in both groups\r\nself-reported by participants aware of their allocation\r\npossible, but unlikely as there was no difference between groups\r\n\r\nThe analysis seems in accordance with the analysis implied by the protocol, although a detailed pre-specified analysis plan was not identified and this particular component of SF-36 was not mentioned in the protocol.\r\nresults are reported for all time points recorded.\r\nThere is no statistically significant difference between groups in the reported outcome."]

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["Unique ID",null,"Study ID",null,"Assessor"]
["Ref or Label",null,"Aim","adhering to intervention (the 'per-protocol' effect)","The effect of adhering to intervention…"]
["Experimental",null,"Comparator",null,"Source"]
["Outcome",null,"Results",null,"Weight"]
["Domain","Signalling question",null,null,"Response","Comments"]
["Bias arising from the randomization process","1.1 Was the allocation sequence random?"]
[null,"1.2 Was the allocation sequence concealed until participants were enrolled and assigned to interventions?"]
[null,"1.3 Did baseline differences between intervention groups suggest a problem with the randomization process?"]
[null,"Risk of bias judgement"]
["Bias due to deviations from intended interventions","2.1 Were participants aware of their assigned intervention during the trial?"]
[null,"2.2 Were carers and people delivering the interventions aware of participants' assigned intervention during the trial?"]
[null,"2.3. [If applicable:] If Y/PY/NI to 2.1 or 2.2: Were important non-protocol interventions balanced across intervention groups?"]
[null,"2.4. [If applicable:] Were there failures in implementing the intervention that could have affected the outcome?"]
[null,"2.5. [If applicable:] Was there non-adherence to the assigned intervention regimen that could have affected participants’ outcomes?"]
[null,"2.6. If N/PN/NI to 2.3, or Y/PY/NI to 2.4 or 2.5: Was an appropriate analysis used to estimate the effect of adhering to the intervention?"]
[null,"Risk of bias judgement"]
["Bias due to missing outcome data","3.1 Were data for this outcome available for all, or nearly all, participants randomized?"]
[null,"3.2 If N/PN/NI to 3.1: Is there evidence that result was not biased by missing outcome data?"]
[null,"3.3 If N/PN to 3.2: Could missingness in the outcome depend on its true value?"]
[null,"3.4 If Y/PY/NI to 3.3: Is it likely that missingness in the outcome depended on its true value?"]
[null,"Risk of bias judgement"]
["Bias in measurement of the outcome","4.1 Was the method of measuring the outcome inappropriate?"]
[null,"4.2 Could measurement or ascertainment of the outcome have differed between intervention groups?"]
[null,"4.3 Were outcome assessors aware of the intervention received by study participants?"]
[null,"4.4 If Y/PY/NI to 4.3: Could assessment of the outcome have been influenced by knowledge of intervention received?"]
[null,"4.5 If Y/PY/NI to 4.4: Is it likely that assessment of the outcome was influenced by knowledge of intervention received?"]
[null,"Risk of bias judgement"]
["Bias in selection of the reported result","5.1 Were the data that produced this result analysed in accordance with a pre-specified analysis plan that was finalized before unblinded outcome data were available for analysis?"]
[null,"5.2 ... multiple eligible outcome measurements (e.g. scales, definitions, time points) within the outcome domain?"]
[null,"5.3 ... multiple eligible analyses of the data?"]
[null,"Risk of bias judgement"]
["Overall bias","Risk of bias judgement"]

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["Unique ID",null,"Study ID",null,"Assessor"]
["Ref or Label",null,"Aim","assignment to intervention (the 'intention-to-treat' effect)\n\n"]
["Experimental",null,"Comparator",null,"Source"]
["Outcome",null,"Results",null,"Weight"]
["Domain","Signalling question",null,null,"Response","Comments"]
["Bias arising from the randomization process","1.1 Was the allocation sequence random?"]
[null,"1.2 Was the allocation sequence concealed until participants were enrolled and assigned to interventions?"]
[null,"1.3 Did baseline differences between intervention groups suggest a problem with the randomization process?"]
[null,"Risk of bias judgement"]
["Bias due to deviations from intended interventions","2.1.Were participants aware of their assigned intervention during the trial?"]
[null,"2.2.Were carers and people delivering the interventions aware of participants' assigned intervention during the trial?"]
[null,"2.3. If Y/PY/NI to 2.1 or 2.2: Were there deviations from the intended intervention that arose because of the experimental context?"]
[null,"2.4 If Y/PY to 2.3: Were these deviations likely to have affected the outcome?"]
[null,"2.5. If Y/PY/NI to 2.4: Were these deviations from intended intervention balanced between groups?"]
[null,"2.6 Was an appropriate analysis used to estimate the effect of assignment to intervention?"]
[null,"2.7 If N/PN/NI to 2.6: Was there potential for a substantial impact (on the result) of the failure to analyse participants in the group to which they were randomized?"]
[null,"Risk of bias judgement"]
["Bias due to missing outcome data","3.1 Were data for this outcome available for all, or nearly all, participants randomized?"]
[null,"3.2 If N/PN/NI to 3.1: Is there evidence that result was not biased by missing outcome data?"]
[null,"3.3 If N/PN to 3.2: Could missingness in the outcome depend on its true value?"]
[null,"3.4 If Y/PY/NI to 3.3: Is it likely that missingness in the outcome depended on its true value?"]
[null,"Risk of bias judgement"]
["Bias in measurement of the outcome","4.1 Was the method of measuring the outcome inappropriate?"]
[null,"4.2 Could measurement or ascertainment of the outcome have differed between intervention groups?"]
[null,"4.3 Were outcome assessors aware of the intervention received by study participants?"]
[null,"4.4 If Y/PY/NI to 4.3: Could assessment of the outcome have been influenced by knowledge of intervention received?"]
[null,"4.5 If Y/PY/NI to 4.4: Is it likely that assessment of the outcome was influenced by knowledge of intervention received?"]
[null,"Risk of bias judgement"]
["Bias in selection of the reported result","5.1 Were the data that produced this result analysed in accordance with a pre-specified analysis plan that was finalized before unblinded outcome data were available for analysis?"]
[null,"5.2 ... multiple eligible outcome measurements (e.g. scales, definitions, time points) within the outcome domain?"]
[null,"5.3 ... multiple eligible analyses of the data?"]
[null,"Risk of bias judgement"]
["Overall bias","Risk of bias judgement"]

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[null,"Journal article(s)","NA","Yes",null,"1.1 Was the allocation sequence random?",null,"2.1 Were participants aware of their assigned intervention during the trial?","2.1 Were participants aware of their assigned intervention during the trial?",null,"3.1 Were data for this outcome available for all, or nearly all, participants randomized?","Individually Randomized, Parallel Group Trials","4.1 Was the method of measuring the outcome inappropriate?","assignment to intervention (the 'intention-to-treat' effect)","5.1 Were the data that produced this result analysed in accordance with a pre-specified analysis plan that was finalized before unblinded outcome data were available for analysis?",null,null,null,"occurance of non-protocol interventions"]
["NA","Trial protocol","Favours experimental ","No (Please include reasons in the note)","Y","1.2 Was the allocation sequence concealed until participants were enrolled and assigned to interventions?","Low","2.2 Were carers and people delivering the interventions aware of participants' assigned intervention during the trial?","2.2 Were carers and people delivering the interventions aware of participants' assigned intervention during the trial?",null,"3.2 If N/PN/NI to 3.1: Is there evidence that the result was not biased by missing outcome data?",null,"4.2 Could measurement or ascertainment of the outcome have differed between intervention groups?","adhering to intervention (the 'per-protocol' effect)","5.2 ... multiple eligible outcome measurements (e.g. scales, definitions, time points) within the outcome domain?",null,null,null,"failures in implementing the intervention that could have affected the outcome"]
["Y","Statistical analysis plan (SAP)","Favours comparator ",null,"PY","1.3 Did baseline differences between intervention groups suggest a problem with the randomization process?","High","2.3 [If applicable:] If Y/PY/NI to 2.1 or 2.2: Were important nonprotocol interventions balanced across intervention groups?","2.3 If Y/PY/NI to 2.1 or 2.2: Were there deviations from the intended intervention that arose because of the trial context?",null,"3.3 If N/PN to 3.2: Could missingness in the outcome depend on its true value?",null,"4.3 If N/PN/NI to 4.1 and 4.2: Were outcome assessors aware of the intervention received by study participants?",null,"5.3 ... multiple eligible analyses of the data?",null,null,null,"non-adherence to their assigned intervention by trial participants"]
["PY","Non-commercial trial registry record (e.g. ClinicalTrials.gov record)","Towards null ",null,"PN",null,"Some concerns","2.4 [If applicable:] Were there failures in implementing the intervention that could have affected the outcome?","2.4 If Y/PY to 2.3: Were these deviations likely to have affected the outcome?",null,"3.4 If Y/PY/NI to 3.3: Is it likely that missingness in the outcome depended on its true value?",null,"4.4 If Y/PY/NI to 4.3: Could assessment of the outcome have been influenced by knowledge of intervention received?"]
["PN","Company-owned trial registry record (e.g. GSK Clinical Study Register record)","Away from null ",null,"N",null,null,"2.5 [If applicable:] Was there non-adherence to the assigned intervention regimen that could have affected participants’ outcomes?","2.5. If Y/PY/NI to 2.4: Were these deviations from intended intervention balanced between groups?",null,null,null,"4.5 If Y/PY/NI to 4.4: Is it likely that assessment of the outcome was influenced by knowledge of intervention received?"]
["N","“Grey literature” (e.g. unpublished thesis)","Unpredictable",null,"NI",null,null,"2.6 If N/PN/NI to 2.3, or Y/PY/NI to 2.4 or 2.5: Was an appropriate analysis used to estimate the effect of adhering to the intervention?","2.6 Was an appropriate analysis used to estimate the effect of assignment to intervention?"]
["NI","Conference abstract(s) about the trial",null,null,null,null,null,null,"2.7 If N/PN/NI to 2.6: Was there potential for a substantial impact (on the result) of the failure to analyse participants in the group to which they were randomized?"]
[null,"Regulatory document (e.g. Clinical Study Report, Drug Approval Package)"]
[null,"Research ethics application"]
[null,"Grant database summary (e.g. NIH RePORTER, Research Councils UK Gateway to Research)"]
[null,"Personal communication with trialist"]
[null,"Personal communication with the sponsor"]