Disability as Mere-Difference and What It Means for Randomized Controlled Trials

People with disabilities are systematically excluded from randomized controlled trials (RCTs). Recent evidence indicates that a substantial proportion of trials contain explicit disability-related exclusion criteria, while nearly half use implicit criteria (e.g., broad comorbidity bans or investigator discretion) that effectively screen out participants with disabilities. Crucially, the vast majority of these explicit exclusions could be overcome through reasonable design adaptations. This article argues that such exclusion reflects not only methodological oversight but also ableist assumptions embedded in research design, regulatory frameworks, and the concept of clinical equipoise. Drawing on Elizabeth Barnes's mere-difference view, which holds that disability represents value-neutral variation in human embodiment rather than an inherent deficit in well-being, we develop three principal contributions. First, we advance an original critique of mere-difference grounded in power relations and standpoint epistemology, arguing that value-neutrality claims require an explicit anti-ableist commitment to avoid obscuring structural injustice. Second, we present a comparative analysis of clinical trial regulations across 10 countries and regions (the United States, the European Union, the United Kingdom, Canada, Japan, Singapore, China, Kenya, Nigeria, and Brazil), demonstrating that unlike gender, age, and race/ethnicity, disability is not subject to mandatory inclusion reporting or exclusion justification requirements. Third, we show how the mere-difference view, appropriately modified, can reshape clinical equipoise by expanding the relevant expert community to include disabled voices and by establishing genuine uncertainty where the standard view forecloses it. We conclude that clinical trial protocols should require explicit justification for disability-based exclusions and that global harmonization efforts, particularly the ICH E6(R3) guidelines, should incorporate explicit language on disability inclusion.