Context Matters—Behind the Scenes of Emergency Clinical Trials in the United States: A Retrospective Observational Analytic Study of Completed Emergency Research Clinical Trials in the United States

Limited information exists on how race, gender, ethnicity & socioeconomic factors impact enrollment in emergency research clinical trials in the US with exception from informed consent (EFIC trials). Consistent underrepresentation of minorities such as lower-than-national population representation of African Americans in traditional clinical trials has been contradicted by sparse evidence of minority over representation in EFIC trials. To study this crucial aspect of EFIC trials, we hypothesized that minority overrepresentation is related to hospital context where EFIC trials occur.

We performed a retrospective observational analytic study of all EFIC trials completed in US as evidenced by mandatory public disclosure in the FDA-1995-S-0036 docket. Trial-level enrollment composition was abstracted to calculate representation ratio (RR), representation difference (RD) & minority enrollment proportions (MEP) while considering hospital (research site) context using CDC, NCHS urban–rural classification schemes & US census data.

Trial-level & population weighted representation metrics (RR, RD, MEP) of 17 EFIC trials was performed from 54 unique EFIC trials identified. 37 were excluded based on prespecified criteria. Median number of participants per trial was 209 [IQR, 100-882], & 4 median sites per trial [IQR 1-11]. EFIC trials were predominantly conducted in moderate to high social vulnerability counties with a median population-weighted SVI 0.68 [IQR 0.33–0.78]. Each 0.1 point increase in SVI was associated with estimated 0.056 increase in the minority enrollment proportion (β=0.56, SE=0.26, p=0.0515), corresponding to ~6 %-point increase per 0.1 SVI indicating positive association between SVI & minority representation.

This study shows that EFIC trials are largely clustered in urban centers & being conducted in more socially vulnerable counties, these studies tend to enroll more minority participants consistently since the inception of FDA’s EFIC regulations. These patterns can reflect both appropriate engagement of high-burden communities & potential concentration of research burden, raising important ethical considerations. These results suggest a heightened importance of using SVI & race/ethnicity distributions prospectively to select sites & setting representation goals at the design stage based on community demographics.