ImportanceDespite federal initiatives encouraging the enrollment of individuals from racial and ethnic minority groups in US clinical trials, no studies to date have specifically examined demographic disparities among participants in phase 1 drug development trials for patients with metastatic cancer.ObjectiveTo assess trends in the enrollment of patients from racial and ethnic minority groups in US phase 1 therapeutic drug trials for metastatic cancer from 2000 to 2018.Design, Setting, and ParticipantsIn this cross-sectional study, ClinicalTrials.gov was queried in July 2021 to identify completed phase 1 drug trials for metastatic cancer in the US from January 1, 2000, to December 31, 2018, with published results, yielding 221 phase 1 trials with 8309 participants aged 18 years or older with metastatic solid tumors. Proportions of each racial and ethnic group of trial participants were compared with that from the North American Association of Central Cancer Registries’ Cancer in North America (CiNA) database. Statistical analysis was performed from July 12, 2021, to March 15, 2022.Main Outcomes and MeasuresFor each racial and ethnic group, the difference between trial and CiNA proportions was examined using a 2-sample test for equality of proportions with continuity correction.ResultsThe 8309 phase 1 trial participants (4198 men [50.5%]; median age, 59 years) included 23 American Indian or Alaska Native participants (0.3%), 371 Asian or Pacific Islander participants (4.5%), 514 Black participants (6.2%), 401 of 5076 Hispanic or Latinx participants (7.9%), and 7154 White participants (86.1%). Industry funded 165 of the 221 trials (74.7%). White patients were overrepresented overall compared with the corresponding CiNA cohort (7154 of 8309 [86.1%] vs 4 113 096 of 4 891 486 [84.1%]; difference, 2.0 percentage points; P < .001). There was an increase in overrepresentation of White patients from 2000 to 2011 (trials, 2780 of 3245 [85.7%]; CiNA, 2 378 019 of 2 800 711 [84.9%]; difference, 0.8 percentage points; P = .23) to 2012-2018 (trials, 4374 of 5063 [86.4%]; CiNA, 1 735 077 of 2 090 775 [82.9%]; difference, 3.5 percentage points; P < .001) and corresponding worsening representation of American Indian or Alaska Native patients (2000-2011: trials, 10 of 3245 [0.3%]; CiNA, 10 905 of 2 800 711 [0.4%]; difference, −0.08 percentage points; 2012-2018: trials, 13 of 5063 [0.3%]; CiNA, 9484 of 2 090 775 [0.5%]; difference, −0.20 percentage points), Asian or Pacific Islander patients (2000-2011: trials, 121 of 3245 [3.7%]; CiNA, 75 033 of 2 800 711 [2.7%]; difference, 1.1 percentage points; 2012-2018: trials, 151 of 5063 [3.0%]; CiNA 70 535 of 2 090 775 [3.4%]; difference, −0.75 percentage points), Black patients (2000-2011: trials, 244 of 3245 [7.5%]; CiNA, 322 701 of 2 800 711 [11.5%]; difference, −4.0 percentage points; 2012-2018: trials, 270 of 5063 [5.3%]; CiNA, 255 625 of 2 090 775 [12.2%]; difference, −6.9 percentage points), and Hispanic or Latinx patients (2000-2011: trials, 161 of 1792 [9.0%]; CiNA, 169 297 of 2 800 711 [6.0%]; difference, 3.0 percentage points; 2012-2018: trials, 240 of 3295 [7.3%]; CiNA, 156 118 of 2 090 775 [7.5%]; difference, −0.2 percentage points). Similar disparities were observed when comparing industry-funded and academic center–sponsored trials.Conclusions and RelevanceIn this cross-sectional study of participants in phase 1 clinical trials of drugs for metastatic cancer, worsening disparities were observed over time in the accrual of patients from racial and ethnic minority groups. These findings may represent widening inequalities in access to trial sites and worsening systemic biases. More efforts are needed to diversify phase 1 cancer drug trials to improve equity in access to new treatments and to ensure that safety and efficacy findings from early drug trials are generalizable across populations.

Purpose: The National Institute of Health has advocated for broad representation of racial and ethnic groups in drug development trials after the introduction of the Revitalization Act in 1993. However, no studies to date have specifically examined demographic disparities among participants in Phase 1 drug development trials. Herein we sought to assess the distribution of and changes in enrollment of racial and ethnic minorities in United States Phase 1 early drug trials for metastatic cancer treatment from 2001 to 2018. Patients and Methods: We queried the ClinicalTrials.gov website to identify completed Phase 1 drug trials in the U.S. from 2001 to 2018 with published results and participants > 18 years of age with metastatic cancer. We reviewed publications from each study to identify racial and ethnic compositions of participants. We compared the proportions of each racial/ethnic group of trial participants to those of corresponding annual incidence data from Surveillance, Epidemiology, and End Results (SEER); for each racial/ethnic group, the difference between trial and SEER proportions was examined using a two-sample test for equality of proportions with continuity correction. Results: We identified a cohort of 236 trials; 72% were industry-sponsored, 19% focused on metastatic breast cancer, 14.8% focused on metastatic colorectal cancer, and 28.3% were basket trials targeting specific genetic pathways with mixed histologies. Of the 9,273 total participants, 81.5% were White, 5.7% Black, 9.4% Asian/Pacific Islander (API), 0.26% American Indian/Alaska Native, and 4.4% Hispanic/Latinx. Comparing the racial/ethnic distributions of trial participants to the corresponding SEER data revealed an excess of White and API representation (1.2% (p<0.005) and 2.3% (p<0.001), respectively), and a 6.2% deficit of Black participants (p<0.001). White patients were overrepresented in clinical trials beginning in 2001-2011 (+4.5% p<0.001)), but not in trials beginning in 2012-2018 (-0.05% p>0.05)). Underrepresentation in trial enrollment worsened in this time period for Black patients (-4.2% to -7.4%, respectively) and Hispanic/Latinx patients (-0.07% to -3.5%). API patients shifted from underrepresentation in 2001-2011 (-2.5%) to overrepresentation in 2012-2018 (+5.52%). Disparities in Black patient enrollment in trials conducted at academic institutions worsened from -4.36% in 2001-2011 to -7.64% in 2012-2018 (p<0.0001). Conclusions: There are persistent and worsening disparities in accrual of racial and ethnic minorities in phase 1 drug trials. These include decreases in enrollment of Black and Hispanic/Latinx patients in clinical trials overall, and in enrollment of Black and AI/AN patients in trials conducted at academic institutions. These findings may represent widening inequalities in access to trial sites, as well as potential systemic biases. Current efforts to diversify clinical trials should expand their reach from phases 2 and 3 to include phase 1, in order to improve equity in access to new treatments at every stage. Citation Format: Hayley M. Dunlop, Evelyn Fitzpatrick, Kevin Kurti, Stephanie Deeb, Erin Gillespie, Fumiko L. Chino, Laura Dover, Cherry Estilo, C. Jillian Tsai. Worsening disparities of racial minority participation in phase 1 early drug development trials in the United States, 2001-2018 [abstract]. In: Proceedings of the AACR Virtual Conference: 14th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2021 Oct 6-8. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr PR-05.