The Role of Diverse Populations in US Clinical Trials

Despite the importance of diversity of cancer trial participants with regard to race, ethnicity, age, and sex, there is little recent information about the representation of these groups in clinical trials. To characterize the representation of racial and ethnic minorities, the elderly, and women in cancer trials sponsored by the National Cancer Institute. Cross-sectional population-based analysis of all participants in therapeutic nonsurgical National Cancer Institute Clinical Trial Cooperative Group breast, colorectal, lung, and prostate cancer clinical trials in 2000 through 2002. In a separate analysis, the ethnic distribution of patients enrolled in 2000 through 2002 was compared with those enrolled in 1996 through 1998, using logistic regression models to estimate the relative risk ratio of enrollment for racial and ethnic minorities to that of white patients during these time periods. Enrollment fraction, defined as the number of trial enrollees divided by the estimated US cancer cases in each race and age subgroup. Cancer research participation varied significantly across racial/ethnic and age groups. Compared with a 1.8% enrollment fraction among white patients, lower enrollment fractions were noted in Hispanic (1.3%; odds ratio [OR] vs whites, 0.72; 95% confidence interval [CI], 0.68-0.77; P<.001) and black (1.3%; OR, 0.71; 95% CI, 0.68-0.74; P<.001) patients. There was a strong relationship between age and enrollment fraction, with trial participants 30 to 64 years of age representing 3.0% of incident cancer patients in that age group, in comparison to 1.3% of 65- to 74-year-old patients and 0.5% of patients 75 years of age and older. This inverse relationship between age and trial enrollment fraction was consistent across racial and ethnic groups. Although the total number of trial participants increased during our study period, the representation of racial and ethnic minorities decreased. In comparison to whites, after adjusting for age, cancer type, and sex, patients enrolled in 2000 through 2002 were 24% less likely to be black (adjusted relative risk ratio, 0.76; 95% CI, 0.65-0.89; P<.001). Men were more likely than women to enroll in colorectal cancer trials (enrollment fractions: 2.1% vs 1.6%, respectively; OR, 1.30; 95% CI, 1.24-1.35; P<.001) and lung cancer trials (enrollment fractions: 0.9% vs 0.7%, respectively; OR, 1.23; 95% CI, 1.16-1.31; P<.001). Enrollment in cancer trials is low for all patient groups. Racial and ethnic minorities, women, and the elderly were less likely to enroll in cooperative group cancer trials than were whites, men, and younger patients, respectively. The proportion of trial participants who are black has declined in recent years.

What is the status of reporting and representation of racial/ethnic groups in landmark trials leading to US Food and Drug Administration (FDA) approval of oncology drugs? In 230 trials leading to FDA oncology drug approvals over the past decade, race was reported in only 145 (63%) trials. Compared with whites (98% of expected proportion), blacks (22% of expected proportion) and Hispanics (44% of expected proportion) were underrepresented in these trials relative to their proportion among the US cancer population. Suboptimal race reporting and representation (especially in blacks and Hispanics) occurs regularly in landmark oncology trials and increased efforts are needed to enhance minority representation and eliminate these disparities. This database study assesses the frequency of race reporting and proportional race representation in trials that support FDA oncology drug approvals. 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. To evaluate the frequency of race reporting and proportional race representation in trials supporting US Food and Drug Administration (FDA) oncology drug approvals. 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. 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 χ 2 tests were used to analyze the data. Proportions and odds ratios (OR) with 95% CIs were reported. 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). 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.

Clinical trials that study cancer are essential for testing the safety and effectiveness of promising treatments, but most people with cancer never enroll in a clinical trial - a challenge exemplified in racial and ethnic minorities. Underenrollment of racial and ethnic minorities reduces the generalizability of research findings and represents a disparity in access to high-quality health care.