Justification of exclusion criteria was underreported in a review of cardiovascular trials

Abstract

Objectives: Ethical guidelines for human subject research require that the burdens and benefits of participation be equally distributed. This study aimed to provide empirical data on exclusion of trial participants and reasons for this exclusion. As a secondary objective, we assessed to what extent exclusion affects generalizability of study results.

Study design and setting: Review of trials on secondary prevention of cardiovascular events.

Results: One hundred thirteen trials were identified, of which 112 reported exclusion criteria. One study justified the exclusion criteria applied. Ambiguous exclusion criteria due to the opinion of the physician (28 of 112 = 25%) or physical disability (12 of 112 = 11%) were reported. Within groups of trials that studied similar treatments (ie, beta-blocker, clopidogrel, or statin therapy), baseline characteristics differed among trials. For example, the proportion of women ranged between 23.1-47.4%, 2.1-38.9%, and 10.6-50.6% for the clopidogrel, beta-blocker, and statin trials, respectively. Nevertheless, no evidence was found for heterogeneity of treatment effects.

Conclusion: Almost none of the articles justified the applied exclusion criteria. No evidence was found that inclusion of dissimilar participants affected generalizability. To allow for a normative discussion on equitable selection of study populations, researchers should not only report exclusion criteria but also the reasons for using these criteria.

Keywords: Ethics; Exclusion criteria; Generalizability; Human experimentation; Medical; Randomized controlled trials; Research.