Associations between methodological quality and representation in clinical trials of systemic lupus erythematosus therapies.

Abstract

BackgroundRandomized clinical trials support drug development and uptake of new therapies for systemic lupus erythematosus (SLE). However, challenges to conducting high-quality clinical trials have been noted, including underrepresentation of minoritized populations. Currently, it is not known whether the methodological quality of clinical trials is associated with representativeness of US patients with SLE.MethodsFor this cross-sectional study, we identified industry-sponsored clinical trials of small molecules and biologics for SLE with at least one US enrollment site, with results published in peer-reviewed journals as of January 1, 2026. Trial characteristics were abstracted, and urbanicity of US enrollment sites were classified using the National Center for Health Statistics Urban-Rural Classification System. Trial representativeness by sex, race, and ethnicity were assessed against SLE prevalence in meta-analyzed US lupus registries using participation-to-prevalence ratios (PPRs; ≥0.8 indicating adequate representation). Trial methodological quality was assessed using the Cochrane Risk of Bias 2 tool. Associations between trial risk of bias and representativeness were evaluated.FindingsWe identified 51 trials enrolling 18,466 participants with SLE. Trial representation was adequate for female (median PPR 1 · 03), Hispanic (median PPR 1 · 37), White (median PPR 1 · 03), and Asian participants (median PPR 2 · 40), and Black participants were underrepresented (median PPR 0 · 32). Most US enrollment sites were located in large metropolitan areas. The methodological quality of trials varied (37% at low risk of bias, 35% with some concerns, 27% at high risk of bias) but was not associated with demographic or geographic representativeness.InterpretationWe identified inconsistencies in participant representation and methodological quality across SLE clinical trials. Although trial designs were generally rigorous, limitations of participant inclusion and enrollment site distribution suggest that representation, rather than methodological quality alone, may limit the external validity of SLE clinical trials.