Associations between Trial Quality and Representation in Clinical Trials of Systemic Lupus Erythematosus Therapies Restricted; Files Only
Leland, Anna (Spring 2026)
Abstract
Background: Randomized clinical trials (RCTs) support drug development and early clinical uptake of new therapies for systemic lupus erythematosus (SLE). However, challenges to conducting high-quality RCTs have been noted, including underrepresentation of minoritized populations. Currently, it is not known whether trial quality is associated with representativeness of the US population with SLE.
Methods: For 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 as 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 quality was assessed using the Cochrane Risk of Bias 2 tool. Associations between trial quality and representativeness were evaluated using Fisher’s exact tests.
Findings: We identified 51 trials enrolling 18,466 participants with SLE. Trial representation was adequate for female (median PPR 1.03), Hispanic (median PPR 1.37), and White (median PPR 1.03) participants, Asian participants were overrepresented (median PPR 2.40), and Black participants were underrepresented (median PPR 0.32). Most US enrollment sites were located in large metropolitan areas. Trial quality 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.
Interpretation: We identified inconsistencies in participant representation and trial quality across SLE clinical trials. Although trial designs were generally rigorous, limitations of participant inclusion and enrollment site distribution suggest that representation, rather than trial quality alone, may limit the external validity of SLE clinical trials.
Table of Contents
Contents
Introduction …………………………………………………………………………………...… 1
Methods …………………………………………………………………………………….…..... 2
Results ……………………………………………………………………………………..……... 7
Discussion ………………………………………………………………………………..……....10
References ………………………………………………………………………………..…….... 15
Illustrations
Figures
1 Flow chart diagram ……………………………………………………………….... 17
2 RCT Risk Designation by Domain ……………………………………………..... 23
Tables
1 Characteristics of Registered and Published Clinical Trials ……….…….... 18
2 Enrollment Characteristics of Registered and Published Clinical Trials … 20
3 Demographic Representation of Participants ……………………………....... 21
4 Cochrane Risk of Bias 2.0 Analyses for Included Clinical Trials ………...... 24
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File download under embargo until 21 May 2027 | 2026-04-15 09:20:35 -0400 | File download under embargo until 21 May 2027 |
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