Errors in Results
Authors: Sean Zheng, Alistair Roddick
Journal: JAMA (2019)

methodological quality and have a higher risk of bias, 2 and including them can exaggerate treatment effects and lead to misleading conclusions. 3Furthermore, small studies have negligible contributions when 2 or more adequately powered studies are included in a meta-analysis. 3These factors may justify the exclusion of small and underpowered studies from meta-analyses in which adequately powered studies already exist. 3 Dr Shah is correct-we unintentionally omitted the TPT 4 and POPADAD 5 studies from the composite cardiovascular outcome.This was due to an unintentional omission from the source file.Both studies were identified from the systematic search and included in all other appropriate analyses.For the composite cardiovascular outcome, inclusion of the POPADAD and TPT studies resulted in no change to the point estimate (hazard ratio [HR], 0.89) or the lower credible interval bound (0.84) and a small change in the upper credible interval bound (from 0.95 to 0.94).We also repeated all other analyses for the composite cardiovascular outcome that were affected (subgroup analyses [high cardiovascular risk populations, participants with diabetes] and sensitivity analyses [total daily dose of 100 mg or less, double-blind placebocontrolled studies, studies published after the year 2000, excluding studies that enrolled participants with asymptomatic peripheral arterial disease, excluding ASCEND]).There were no changes in statistical significance, with only minor changes in the point estimates, CIs or credible intervals, and/or numbers needed to treat.The article has been corrected online.While the inclusion of summed event counts for composite outcomes when composite data are not available is a recognized method in meta-analysis, it is a source of potential bias because participants may experience multiple events.An alternative analysis excluding studies with summed composite outcome data did not influence the primary cardiovascular outcome (HR, 0.89 [95% credible interval,).The ETDRS randomized 3711 participants with diabetes and evidence of diabetic retinopathy. 6The study did not formally exclude participants with cardiovascular disease, which often coexists with diabetic retinopathy.There was a high frequency of underlying cardiovascular disease in the ETDRS, with 1812 of 3711 participants (49%) having a history of cardiovascular disease.The ETDRS was therefore excluded from the analysis on the basis that it did not represent a population without preexisting cardiovascular disease as required in our inclusion criteria.Regarding differences in the event counts, for ASCEND, the total myocardial infarction count was derived from the nonfatal myocardial infarction and coronary death event counts.For TPT, we elected to include all ischemic heart disease events (coronary death, fatal and nonfatal myocardial infarction) for the myocardial infarction outcome in agreement with the study authors' assessment that "there was often little distinction between the clinical and pathological characteristics" of coronary and myocardial infarction deaths. 4Using the values that Shah quotes may underestimate myocardial infarction events in TPT.