Race/ethnicity reporting and representation in US clinical trials: a cohort study

Abstract

Background: Systemic progress in improving trial representation is uncertain, and previous analyses of minority trial participation have been limited to small cohorts with limited exploration of driving factors.

Methods: We analyzed detailed trial records from all US clinical trials registered in ClinicalTrials.gov from March 2000 to March 2020. Minority enrollment was compared to 2010 US Census demographic estimates using Wilcoxon test. We utilized logistic regression and generalized linear regression with a logit link to assess the association of possible drivers (including trials' funding source, size, phase, and design) with trials' disclosure of and amount of minority enrollment respectively.

Findings: Among 20,692 US-based trials with reported results (representing ~4·76 million enrollees), only 43% (8,871/20,692) reported any race/ethnicity data. The majority of enrollees were White (median 79·7%; interquartile range [IQR] 61·9-90·0%), followed by Black (10·0%; IQR 2·5-23·5%), Hispanic/Latino (6·0%; IQR 0·43-15·4%), Asian (1·0%; IQR 0·0-4·1%), and American Indian (0·0%; IQR 0·0-0·2%). Median combined enrollment of minority race/ethnicity groups (Black, Hispanic/Latino, Asian, American Indian, Other/Multi) was below census estimates (27·6%) (p<0·001) however increased at an annual rate of 1·7%. Industry and Academic funding were negatively associated with race/ethnicity reporting (Industry adjusted odds ratio [aOR]: 0·42, 95% confidence interval [CI]: 0·38 to 0·46, p<0.0001; Academic aOR: 0·45, CI: 0·41 to 0·50, p<0.0001). Industry also had a negative association with the proportion of minority ethnicity enrollees (aOR: 0·69, CI: 0·60 to 0·79) compared to US Government-funded trials.

Interpretation: Over the past two decades, the majority of US trials in ClinicalTrials.gov do not report race/ethnicity enrollment data, and minorities are underrepresented in trials with modest improvement over time.

Funding: Stanford Medical Scholars Research Funding, the National Heart, Lung, and Blood Institute, NIH (1K01HL144607) and the American Heart Association/Robert Wood Johnson Medical Faculty Development Program.

Figure 1

CONSORT Diagram of Clinical Trials Included in the Analysis. The FDAAA 801 refers to the 27 September 2007 enactment of Section 801 of the Food and Drug Administration Amendments Act which required a subset of US phase 2-4 trials to report results in ClinicalTrials.gov and established reporting guidelines for clinical trials. The Final Rule refers to the 18 January 2017 Food and Drug Administration clarification and expansion of reporting requirements for clinical trials in Clinicaltrials.gov including race/ethnicity reporting. Irregularities that were not amenable to analysis included data entry errors and illogical data responses.

Figure 2

Race and ethnicity enrollment reporting in United States-based clinical trials registered on ClinicalTrials.gov. Panel A shows change over time in proportion of trials reporting race/ethnicity enrollment data. All Five Race/Ethnicity Groups include White, Latino, Black, Asian (including Pacific Islander and Native Hawaiian), and American Indian (including Alaskan Native). Panel B shows the races/ethnicities that were reported among trials that included any race/ethnicity enrollment results data and the proportion of those trials that reported each individual race/ethnicity.

Figure 3

Race/ethnicity representation among all United States-based clinical trials with race/ethnicity enrollment data in Clinicaltrials.gov. The graph shows the distribution of trials and the representation of each racial/ethnic group organized by racial/ethnic category. Distribution only includes trials that reported data for all five racial/ethnic groups. Census calculations reflect 2010 US Census data.

Figure 4

Association of trial features with enrollment of racial/ethnic groups. Each unit shows the adjusted relative difference and the 95% confidence interval for that variable. On ClinicalTrials.gov “Not Applicable” is used to describe trials without Food and Drug Administration-defined phases, including trials of devices or behavioral interventions. Funding categories were determined with data on the sponsor and collaborators. Industry funding includes trials with an industry sponsor or collaborating agency US Government trials include remaining trials with a US Government sponsor or collaborating agency.