BMI and weight-based eligibility criteria in drug-development trials: A systematic search and ethical analysis

Individuals with overweight and obesity represent the majority of U.S. adults, yet they are disproportionately excluded from clinical trials, particularly drug-development studies. Such exclusions raise serious ethical concerns related to justice and fair subject selection, while simultaneously compromising the generalizability of drug safety and efficacy. To better understand the scope of this issue, we conducted a systematic search of 251 active U.S.-based interventional drug-development trials registered on ClinicalTrials.gov. Among these, 186 (74.1%) studies used BMI-and/or-weight-based (BWB) eligibility criteria: 83 (44.4%) with BMI cutoffs only, 12 (6.4%) with weight cutoffs only, and 91 (49.2%) with both. BMI thresholds varied widely and frequently diverged from standard clinical categories. Only three (1.2%) studies offered an explicit justification for the criteria in publicly accessible documents. Meanwhile, 65 (25.9%) studies imposed no BWB limits, suggesting such exclusions are not universally believed to be necessary. We argue that BWB exclusions are not merely methodological deficits but expressions of structural injustice within research governance. Our descriptive analysis provides a foundation for future evaluation of whether such exclusions are scientifically or ethically justifiable. Inclusion of marginalized groups is a critical requirement for producing valid scientific knowledge and ethical clinical research. Oversight bodies, sponsors, institutions, and investigators must treat BWB criteria with careful discretion, requiring transparent justification and proactive inclusion to ensure justice, rigor, and equity in clinical research.