A methods review of posttrial follow-up studies of cardiovascular prevention finds potential biases in estimating legacy effects

Objectives The objective of the study was to assess the methods used, and potential for bias, in posttrial studies of cardiovascular disease (CVD) where legacy effects may be estimated. Study Design and Setting We undertook a methods review of posttrial studies after randomized controlled trials (RCTs) of interventions to prevent CVD. For each included article, we extracted information on important aspects of the design and analysis of the study, and on the reporting of legacy effects. Results Of 2,622 retrieved articles, 46 were included in the review: 13 on blood glucose control, 13 on blood pressure control, and 20 on blood lipid control. The median duration for the RCT and posttrial follow-up studies was 5.0 and 5.7 years, respectively. At least 80% of initial RCT participants were enrolled in the posttrial study in 32 of the reports. Most reports used both linkage to routine administrative data sources and active data collection for the posttrial study. Of the 46 included articles, the authors assessed and reported posttrial covariate balance in 29 and made statistical adjustments in the analysis for potential confounding in 25. Posttrial results were reported separately to overall results (from time of randomization) in 21 articles. Legacy effects were claimed in 19 reports, of which 16 could be justified on the basis of the posttrial results. Conclusion Posttrial studies may provide valuable information for investigating legacy effects, but better reporting of results is needed to realize their full potential. Robust methods of data collection and analysis may address the risk of selection and confounding biases in posttrial studies.