A population study of clinical trial accrual for women and minorities in neuro-oncology following the NIH Revitalization Act

Abstract

Background: The NIH Revitalization Act, implemented 29 years ago, set to improve the representation of women and minorities in clinical trials. In this study, we investigate progress made in all phase therapeutic clinical trials for neuroepithelial CNS tumors stratified by demographic-specific age-adjusted disease incidence and mortality. Additionally, we identify workforce characteristics associated with clinical trials meeting established accrual benchmarks.

Methods: Registry study of published clinical trials for World Health Organization defined neuroepithelial CNS tumors between January 2000 and December 2019. Study participants were obtained from PubMed and ClinicalTrials.gov. Population-based data originated from the CBTRUS for incidence analyses. SEER-18 Incidence-Based Mortality data was used for mortality analysis. Descriptive statistics, Fisher exact, and χ 2 tests were used for data analysis.

Results: Among 662 published clinical trials representing 49 907 participants, 62.5% of participants were men and 37.5% women (P < .0001) representing a mortality specific over-accrual for men (P = .001). Whites, Asians, Blacks, and Hispanics represented 91.7%, 1.5%, 2.6%, and 1.7% of trial participants. Compared with mortality, Blacks (47% of expected mortality, P = .008), Hispanics (17% of expected mortality, P < .001) and Asians (33% of expected mortality, P < .001) were underrepresented compared with Whites (114% of expected mortality, P < .001). Clinical trials meeting accrual benchmarks for race included minority authorship.

Conclusions: Following the Revitalization Act, minorities and women remain underrepresented in therapeutic clinical trials for neuroepithelial tumors, relative to disease incidence and mortality. Study accrual has improved with time. This study provides a framework for clinical trial accrual efforts and offers guidance regarding workforce considerations associated with enrollment of underserved patients.

Keywords: clinical trial accrual; clinical trials; disparities; glioma.

Fig. 1

Proportions of men and women enrolled in a clinical trial 2000–2019, compared to incidence and mortality burden. A. Clinical trial accrual proportions in men and women over the 20-year period, 2000–2019. Men represented 62.3% of accrued participants, women 37.7% (P < .0001) B. Proportions of accrued participants as compared to disease incidence and mortality. Men were disproportionately accrued compared to their disease burden (P = .001), and women were under-accrued compared to their disease burden (P = .001). C. Five-year trends from 2000 to 2019 show consistently significant results across the time period. *Data Source: Incidence—CBTRUS: Data provided by CDC’s National Program of Cancer Registries and NCI’s Surveillance, Epidemiology and End Results Program, 2000–2017, Mortality—Incidence-Based Mortality SEER Research Data, (2000–2017), Accrual—Systematic review of the literature published of clinical (Phase I–IV) trials of adult gliomas (2000–2019).

Fig. 2

Patient proportions for incidence, mortality, and accrual according to minority* identity, 20-year average and five-year trends 2000–2019. A. Patient proportions for incidence, mortality, and accrual according to Minority* identity, 2000–2019. White participants represented 91.7% of accrued participants, Minority 5.9% (P < .001). White patients were disproportionately accrued compared to their disease burden (P < .001), and Minority patients were under-accrued compared to their disease burden (P < .001). B. Five-Year Trends from 2000 to 2019 show consistently significant results across the time period. *Data Source: Incidence—CBTRUS: Data provided by CDC’s National Program of Cancer Registries and NCI’s Surveillance, Epidemiology and End Results Program, 2000–2017, Mortality—Incidence-Based Mortality SEER Research Data, (2000–2017), Accrual—Systematic review of the literature published of clinical (Phase I–IV) trials of adult gliomas (2000–2019). **Minority status determined by identification with an NIH-defined group.

Fig. 3

Clinical trial enrollment by race and ethnicity in articles published from 2000 to 2019. White participants, on average, accounted for 91.7% of enrolled participants over the 20-year period. Under-represented minorities as a group, accounted for 5.9% of enrolled participants (Black/African American: 2.6%, Asian/Pacific Islander: 1.5%, Hispanic/Latino: 1.7%, Native American/Alaska Native: 0.1%). URM: Under-represented minority.

Fig. 4

Patient proportions for incidence, mortality, and accrual according to race and ethnicity, 2000–2019. Over the 20-year period, White patients were disproportionately-accrued compared to their mortality burden 114% of expected (P < .001), their minority counterparts were significantly under-accrued; Black/African-American 47% of expected (P = .008), Hispanic/Latino 17% of expected (P < .001), Asian/Pacific Islander 33% of expected (P < .001) and Native American/Alaska Native 20% of expected (P = .008). PI: Pacific Islander, AI: Alaska Native. *Data Source: Incidence—CBTRUS: Data provided by CDC’s National Program of Cancer Registries and NCI’s Surveillance, Epidemiology and End Results Program, 2000–2017, Mortality—Incidence-Based Mortality SEER Research Data, (2000–2017), Accrual—Systematic review of the literature published of clinical (Phase I–IV) trials of adult gliomas (2000–2019).

Fig. 5

Five-year grouped trend data for incidence, mortality and accrual by minority* status 2000–2019. Five-Year Trends from 2000 to 2019 shows increased accrual for minority patients from 3.2% (2000–2004) to 8.2% (2015–2019) over the 20 year period. *Data Source: Incidence—CBTRUS: Data provided by CDC’s National Program of Cancer Registries and NCI’s Surveillance, Epidemiology and End Results Program, 2000–2017, Mortality—Incidence-Based Mortality SEER Research Data, (2000–2017), Accrual—Systematic review of the literature published of clinical (Phase I–IV) trials of adult gliomas (2000–2019).