Background: Subgroup analyses in randomized trials examine whether effects of interventions differ between subgroups of study populations according to characteristics of patients or interventions. However, findings from subgroup analyses may be misleading, potentially resulting in suboptimal clinical and health decision making. Few studies have investigated the reporting and conduct of subgroup analyses and a number of important questions remain unanswered. The objectives of this study are: 1) to describe the reporting of subgroup analyses and claims of subgroup effects in randomized controlled trials, 2) to assess study characteristics associated with reporting of subgroup analyses and with claims of subgroup effects, and 3) to examine the analysis, and interpretation of subgroup effects for each study's primary outcome. Methods: We will conduct a systematic review of 464 randomized controlled human trials published in 2007 in the 118 Core Clinical Journals defined by the National Library of Medicine. We will randomly select journal articles, stratified in a 1:1 ratio by higher impact versus lower impact journals. According to 2007 ISI total citations, we consider the New England Journal of Medicine, JAMA, Lancet, Annals of Internal Medicine, and BMJ as higher impact journals. Teams of two reviewers will independently screen full texts of reports for eligibility, and abstract data, using standardized, pilot-tested extraction forms. We will conduct univariable and multivariable logistic regression analyses to examine the association of pre-specified study characteristics with reporting of subgroup analyses and with claims of subgroup effects for the primary and any other outcomes. Discussion: A clear understanding of subgroup analyses, as currently conducted and reported in published randomized controlled trials, will reveal both strengths and weaknesses of this practice. Our findings will contribute to a set of recommendations to optimize the conduct and reporting of subgroup analyses, and claim and interpretation of subgroup effects in randomized trials.
Bibliographical noteFunding Information:
We thank Monica Owen for administrative assistance. We thank Aravin Duraik for developing the study electronic forms. The study is partially supported by the National Natural Science Foundation of China (NSFC, 70703025). The funder had no role in the study design, in the writing of the manuscript, or in the decision to submit this or future manuscripts for publication. Xin Sun is supported by two research scholarships from the National Natural Science Foundation of China (70503021, 70703025). Matthias Briel was supported by a scholarship from the Swiss National Science Foundation (PASMA-112951/1) and the Roche Research Foundation. Dominik Mertz was partially supported by a research scholarship from the Swiss National Science Foundation (PBBSP3-124436). Jason Busse is funded by a New Investigator Award from the Canadian Institutes of Health Research and Canadian Chiropractic Research Foundation.