Racial and sex representation in clinical trials: Where are we in abdominal organ transplantation?

To the Editor: Clinical trials have historically failed to reflect the diversity of patients who may ultimately benefit from interventions being studied.1, 2 Lack of diversity among trial participants can underestimate the effects of biological variation in treatment effect and further reduce equity and access to evidence-based healthcare for minority patients.3 The NIH and FDA implemented the Revitalization Act of 1993 to address these issues and provide guidelines to promote the inclusion of women and minorities in clinical trials.4 Disparities in transplant outcomes among recipients from racial and ethnic minorities are well established.5 A recent study highlighted sex and racial disparities in cardiovascular trial enrollment, including heart transplantation.6 Given the paucity of literature exploring minority representation among abdominal transplant trial participants, this study investigates the enrollment of women and minorities in trials involving liver (LT) and kidney transplantation (KT). Retrospective review of clinicaltrials.gov was performed. US clinical trials listed as “completed” or “active but not recruiting” involving LT and KT recipients were included, with trial start dates from August 2000 to August 2018. To assess the representation of minorities and women, the prevalence-to-participation ratio (PPR) was calculated by dividing the percent of a population represented within the trial enrollment by the percent of that population of US transplant recipients from 2000 to 2018 obtained from the Scientific Registry of Transplant Recipients. PPR <0.8 or >1.2 denotes underrepresentation or overrepresentation, respectively. During the study period, 172 clinical trials were conducted in the United States involving 67 394 KT (91.8%) and LT (8.2%) recipients, of which 40.8% were women (41.2% in KT and 29% in LT studies). Most participants were 18–65 years of age (84.5%). Participants were 56.7% White, 38% Black, 12.5% Hispanic, 2.9% Asian, and 1.7% other/unknown. American Indian/Alaskan Native, Pacific Islander, mixed, and other/unknown comprised <1% of participants (Table 1A). Transplant clinical trials included were industry-based (32%), mixed funding (30%), or NIH funded (9.3%) (Table 1B). PPR were within acceptable range for age and sex. Ethnic and racial minorities were largely underrepresented, with a PPR of 0.736 for Hispanic ethnicity (0.578 for renal studies); 0.258 for Asian participants (0.150 in KT studies); and 0.813 for Black participants (0.762 in KT trials; Table 1C). None of these demographic groups showed a change in PPR trends over time from 2000 to 2018 (data not shown). This study demonstrates that underrepresentation of Hispanic, Black, and Asian races has persisted over two decades of transplant clinical trials. This disparity was most common in KT trials, which account for the majority of trials examined and represents the most common solid organ transplant performed in the US. We further examined PPR of studies by year to evaluate trends of representation over time; however, disparities persisted, suggesting that modern transplant trials continue to under enroll patients from diverse populations. It is possible that practical aspects of study design and implementation, including non-English informed consent, recruitment materials, and surveys, create additional barriers to ensuring diverse study enrollment, and these should be addressed in study document design. Future study should evaluate which factors contribute to these disparities, including willingness to participate in research, geographic variations, recruitment strategies, and community engagement of trial administrators. Equitable representation of diverse populations in transplant clinical trials is essential for providing high-quality, evidence-based care to all patients. Participation in clinical trials has been shown to increase access to state-of-the-art care for minority populations, and this should continue to be explored in the context of solid organ transplantation.7, 8 It is imperative that emerging clinical trials in solid organ transplantation implement strategies, for example, the PROGRESS Plus framework, to recruit an adequately diverse patient population.9 The authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation. The data that support the findings of this study are openly available in clinicaltrials.gov.