Disparity of Race Reporting and Representation in Clinical Trials Leading to Cancer Drug Approvals From 2008 to 2018

Abstract

Importance: Representative racial/ethnic participation in research, especially in clinical trials that establish standards of care, is necessary to minimize disparities in outcomes and to uphold societal equity in health care.

Objective: To evaluate the frequency of race reporting and proportional race representation in trials supporting US Food and Drug Administration (FDA) oncology drug approvals.

Design, setting, and participants: Database study of all reported trials supporting FDA oncology drug approvals granted between July 2008 and June 2018. Primary reports of trials were obtained from PubMed and ClinicalTrials.gov. Food and Drug Administration approvals were identified using the FDA archives. The US population-based cancer estimates by race were calculated using National Cancer Institute-Surveillance, Epidemiology, and End Results and US Census databases.

Main outcomes and measures: Primary outcomes were the proportion of trials reporting race and the proportion of patients by race participating in trials. Secondary outcomes included race subgroup analyses reporting and gaps between race proportion in trials and the US population. Descriptive statistics, Fisher exact, and χ2 tests were used to analyze the data. Proportions and odds ratios (OR) with 95% CIs were reported.

Results: Among 230 trials with a total of 112 293 participants, 145 (63.0%) reported on at least 1 race, 18 (7.8%) documented the 4 major races in the United States (white, Asian, black, and Hispanic), and 58 (25.2%) reported race subgroup analyses. Reporting on white, Asian, black, and Hispanic races was included in 144 (62.6%), 110 (47.8%), 88 (38.2%), and 23 (10.0%) trials, respectively. Between July 2008 and June 2013 vs July 2013 and June 2018, the number of trials reporting race (45 [56.6%] vs 100 [67.1%]; OR, 1.63; 95% CI, 0.93-2.87; P = .09) and race subgroup analysis (13 [16.1%] vs 45 [30.2%]; OR, 2.26, 95% CI, 1.16-4.67; P = .03) changed minimally and varied across races. Whites, Asians, blacks, and Hispanics represented 76.3%, 18.3%, 3.1% and 6.1% of trial participants, respectively, and the proportion for each race enrolled over time changed nominally (blacks, 3.6% vs 2.9% and Hispanics, 5.3% vs 6.7%) from July 2008 to June 2013 vs July 2013 to June 2018. Compared with their proportion of US cancer incidence, blacks (22% of expected) and Hispanics (44% of expected) were underrepresented compared with whites (98% of expected) and Asians (438% of expected).

Conclusions and relevance: Race and race subgroup analysis reporting occurs infrequently, and black and Hispanic races are consistently underrepresented compared with their burden of cancer incidence in landmark trials that led to FDA oncology drug approvals. Enhanced minority engagement is needed in trials to ensure the validity of results and reliable benefits to all.

Conflict of interest statement

Conflict of Interest Disclosures: None reported.

Figures

Figure 1.. Study Schema and Race Reporting in FDA Approvals in Hematology/Oncology

A, The US Food and Drug Administration (FDA) approved 108 drugs in 204 distinct approvals based on 232 clinical trials. B, Drug approvals increased over the past 10 years (2008 to 2018). Less than 50% of the trials leading to these approvals reported on other than white races. C, The absolute number of patients of races other than white who participated in pivotal trials leading to FDA approval was considerably low. aFDA hematology/oncology (cancer) approvals and safety notifications. bData obtained from principal publication of trials. A total of 227 reports were retrieved using PubMed (1 approval was based on 2 trials had no available reports at data lock on December 1, 2018. It was excluded from the analyses). cHispanic origin was reported both as race and as ethnicity across different studies and has been combined for analyses in the present study. Therefore, Hispanics and non-Hispanics are not mutually exclusive from whites, blacks, Asians, and Native Americans. d2008 and 2018 Approval data limited to second-half and first-half of years, respectively. eTotal populations specified per race enrolled across 144 trials reporting on race expressed to scale. The size of sphere represents the absolute number of patients.

Figure 2.. Race Reporting and Race-Related Subgroup Analyses in Trials for FDA Approval of Hematology/Oncology Drugs

A, The charts show a trend over past 10 years in trials leading to US Food and Drug Administration (FDA) drug approvals with regard to the proportion of trials reporting on race/ethnicity (A) and the proportion of trials reporting on subgroup analysis pertaining to race/ethnicity (B). Although the sharp increase in the number of trials leading to FDA-approved drugs has been increasing over time, there has been a relatively smaller improvement in reporting of race or subgroup analyses based on race, and these reporting rates vary significantly between races. The overall reporting of race and race subgroup analyses remains low even in 2018.

Figure 3.. Differences in Incidence, Mortality, and Enrollment in Clinical Trials Leading to FDA Oncology Drug Approvals vs US Population With Cancer

A, Proportion of different races in trials for US Food and Drug Administration (FDA) approval from 2008 to 2018. B, Relative proportion of different races (pertaining to incidence and mortality) among patients with cancer in the United States was estimated using the Surveillance, Epidemiology, and End Results database and compared with trial participants in FDA approval trials between July 2008 and June 2018. Representation of black and Hispanic patients in pivotal FDA approval studies was low from 2008 to 2018.

Figure 4.. Relative Differences in Incidence, Mortality, and Enrollment in Clinical Trials Leading to FDA Drug Approval for Specific Indications

The proportion of different races represented in trials for US Food and Drug Administration (FDA) approval of oncology drugs for specific indications compared with the proportion of different races (pertaining to incidence [I] and mortality [M]) among patients with a specific cancer vs the US population estimated using data from the Surveillance, Epidemiology, and End Results database. Analysis was restricted to indications where trials (>1) reported on white, Asian, and black races. There is consistent underrepresentation of black and Hispanic races in pivotal FDA approval studies between July 2008 and June 2018. CML indicates chronic myeloid leukemia; HL, Hodgkin lymphoma; NHL, non-Hodgkin lymphoma.