Assessment of Potential Barriers to Inclusion in Randomized Clinical Trials Published in Top General and Internal Medical Journals

Background: Racial and ethnic minority groups are underrepresented in clinical research. Racially diverse individuals that speak languages other than English or have limited proficiency may be hindered fromparticipation in randomized clinical trials (RCTs) through eligibility criteria. Objective:To assess English language requirements for enrollment in registered and published RCTs as well as readability of eligibility criteria. Design: Cross-sectional study of RCTs on heart disease, stroke, cancer, asthma, influenza and pneumonia, diabetes, HIV/AIDS, and COVID-19 drug interventions retrieved from MEDLINE, Scopus, Epistemonikos, EBSCOHost, COVID-19 evidence, Web of Science Core Collection, and the WHO COVID-19 databases. Included published RCTs were: (1) within the top 10 first-quartile general and internal medicine journals in2017 with at least 1 US site; (2) published between 2017 and 2022; and (3) registered on ClinicalTrials.gov with eligibility criteria in protocols. Eligibility criteria in protocols, informed consent forms, and ClinicalTrials.gov were assessed for indications that English was an enrollment requirement. Readability was assessed with Flesch-Kincaid grade (FKG) level (ranges from grades 0 to 18) and Gunning-Fog (GF) (ranges from grades 0 to 20 [college graduate]), where lower grades correspond to easier readability. Reporting of participant race and concordance between articles and ClinicalTrials.gov were determined. Results:Total of 39 of 6394 RCTs from Annals of Internal Medicine (n = 1), JAMA (n = 14), JAMA Internal Medicine (n = 3), Lancet (n = 11), PLoS Medicine (n = 1), and New England Journal of Medicine (n = 8). Trials mostly did not disclose which language was required for enrollment of participants reported as: American Indian (median [range], 0 [0-4]), Asian (14 [6-69], Black (median [range], 54 [36-106]), Latinx (45 [4-127]), and White (250 [108-513]). Regardless of funder and disease, median [IQR] FKG and GF of eligibility criteria were higher than the recommended sixth grade in protocols (11.5 [10.7-13.0] and 13.0 [11.7-14.5]) and ClinicalTrials.gov (13.0 [11.0-14.0] and 13.7 [11.7-14.7]), respectively. There were 17 (44%) RCTs that had at least 1 difference in the reporting of race in the article and ClinicalTrials.gov. Conclusions:There was low explicit reporting of required languages for enrollment in RCT eligibility criteria; and readability levels of protocols were high. Ethics committees and funders should obligate inclusion of explicit reporting of languages and high readability of RCT information. Responsibility rests with ethics committees, funders, and trialists to conceive inclusive trials to strive toward health equity.