Clinical Trial Diversity-Will We Know It When We See It?

This Editorial discusses the existing policy efforts in the US for ensuring adequate racial and ethnic diversity in clinical trials, identifies barriers to consistency and acceptable representation, and suggests measures to address them.

Metrics, baseline scores, and a tool to improve sponsor performance on clinical trial diversity: retrospective cross sectional study.

Objective: To develop a measure for fair inclusion in pivotal trials by assessing transparency and representation of enrolled women, older adults (aged 65 years and older), and racially and ethnically minoritized patients. Design: Retrospective cross sectional study. Population: Sponsors of novel oncology therapeutics that were approved by the US Food and Drug Administration over 1 January 2012 to 31 December 2017. Data sources: Trial data from Drugs@FDA, ClinicalTrials.gov, and corresponding publications; cancer incidence demographics from US Cancer Statistics and the American Cancer Society. Main outcome measures: Transparency measures assess whether trials publicly report participant sex, age, and racial and ethnic identity. Representation measures assess whether trial participant demographics represent more than 80% of the US patient population for studied conditions, calculated by dividing the percentage of study participants in each demographic subgroup by the percentage of the US cancer population with the studied condition per group. Composite fair inclusion measures assess average transparency and representation scores, overall and for each demographic group. Results are reported at the trial, product, and sponsor levels. Results: Between 1 January 2012 and 31 December 2017, the FDA approved 59 novel cancer therapeutics, submitted by 25 sponsors (all industry companies) on the basis of 64 pivotal trials. All 25 sponsors (100%) reported participant sex, 10 (40%) reported age, and six (24%) reported race and ethnicity. Although 14 (56%) sponsors had adequate representation of women in trials, only six (24%) adequately represented older adults, and four (16%) adequately represented racially and ethnically minoritized patients (black, Asian, Hispanic or Latinx). On overall fair inclusion, one sponsor scored 100% and the median sponsor score was 81% (interquartile range 75-87%). More than half of sponsors (13 (56%) of 25) fairly included women, 20% (n=5) fairly included older adults, and 4% (n=1) fairly included racially and ethnically minoritized patients in trials. 80% of product had pivotal trials that fairly included women, 24% fairly included older adults, and 5% fairly included racially and ethnically minoritized patients. Conclusions: This novel approach evaluates trials, products, and sponsors on their fair inclusion of demographic groups in research. For oncology trials, substantial room was noted for improved inclusion of older adults and patients who identify as black or Latinx and transparency around the number of participants identifying as Native Hawaiian, Pacific Islander, American Indian, and Alaska Native. These measures can be used by sponsors, ethics committees, among others, to set and evaluate trial diversity goals to help spur progress toward greater research equity in the US.

Reporting of Study Participant Demographic Characteristics and Demographic Representation in Premarketing and Postmarketing Studies of Novel Cancer Therapeutics.

Importance: Adequate representation of demographic subgroups in premarketing and postmarketing clinical studies is necessary for understanding the safety and efficacy associated with novel cancer therapeutics. Objective: To characterize and compare the reporting of demographic data and the representation of individuals by sex, age, and race in premarketing and postmarketing studies used by the Food and Drug Administration (FDA) to evaluate novel cancer therapeutics. Design, Setting, and Participants: In this cross-sectional study, premarketing and postmarketing studies for novel cancer therapeutics approved by the FDA from 2012 through 2016 were identified. Study demographic information was abstracted from publicly available sources, and US cancer population demographic data was abstracted from US Cancer Statistics. Analyses were conducted from February 25 through September 21, 2020. Main Outcomes and Measures: The percentages of trials reporting sex, age, and race/ethnicity were calculated, and participation to prevalence ratios (PPRs) were calculated by dividing the percentage of study participants in each demographic group by the percentage of the US cancer population in each group. PPRs were constructed for premarketing and postmarketing studies and by cancer type. Underrepresentation was defined as PPR less than 0.8. Results: From 2012 through 2016, the FDA approved 45 cancer therapeutics. The study sample included 77 premarketing studies and 56 postmarketing studies. Postmarketing studies, compared with premarketing studies, were less likely to report patient sex (42 studies reporting [75.0%] vs 77 studies reporting [100%]; P < .001) and race (27 studies reporting [48.2%] vs 62 studies reporting [80.5%]; P < .001). Women were adequately represented in premarketing studies (mean [SD] PPR, 0.91; 95% CI, 0.90-0.91) and postmarketing studies (mean PPR, 1.00; 95% CI, 1.00-1.01). Although older adults and Black patients were underrepresented in premarketing studies (older adults: mean PPR, 0.73; 95% CI, 0.72-0.74; Black patients: mean PPR, 0.32; 95% CI, 0.31-0.32), these groups continued to be underrepresented in postmarketing studies (older adults: mean PPR, 0.75; 95% CI, 0.75-0.76; Black patients: mean PPR, 0.21; 95% CI, 0.21-0.21). Conclusions and Relevance: This study found that older adults and Black patients were underrepresented in postmarketing studies of novel cancer therapeutics to a similar degree that they were underrepresented in premarketing studies. These findings suggest that postmarketing studies are not associated with improvements to gaps in demographic representation present at the time of FDA approval.