Overcoming Lack of Diversity in Cardiovascular Clinical Trials

Abstract

Our current cardiovascular research paradigm has served us well for decades, facilitating the approvals of new drugs and devices that have unequivocally advanced the treatment of cardiovascular disease. While it may be argued that patient het-erogeneity is a nuanced, rather than critical, component of drug or device efficacy, it is unquestionable that the current standard of care emanates from randomized controlled trials that have failed to fully represent elderly patients, minorities, and women. 1 The lack of adequate data for these relevant subgroups challenges the integrity of our evidence-based care algorithms and questions the replication of favorable safety and outcomes across all populations. These persistent missteps in our evidence-based generation could permit less than ideal health outcomes as a function of sex, age, race, and ethnicity. Given the rapidly changing demographics in our society, addressing these gaps in our evidence base is therefore not only a social imperative, but also a clinical necessity and important business consideration if we are to provide optimal care to an increasingly diverse US patient population. THE REGULATORY CONUNDRUM As part of the 2012 US Food and Drug Administration (FDA) Safety and Innovation Act, a legislative directive emerged to address diversity in clinical trials and the impact of age, sex, and race/ethnicity on the safety and efficacy of newly approved drugs. A key programmatic output was the FDA Drug Trials Snapshots program, which shed light on the demographics of patients enrolled in pivotal trials that lead to new drug approvals. 1 Of the 53 533 patients who participated in FDA registered cardiovascular drug trials from 2015 to 2016, geography unexpectedly emerged as yet another dispa-rate variable, with US enrollment representing only 16% of patients, while the outside US population constituted 84% of patients enrolled in pivotal trials. Though expediting enrollment, the unintended consequence of the continued globalization of clinical trials is an even more stark underrepresentation of US patient populations. For example, for all FDA drug trials completed in 2015 to 2016, only 1.3% of non-US study participants were African American, while this proportion was nearly 15% for participants enrolled in the United States 1 (a proportion that mirrors current US Census Bureau demographics and is indicative of progress in US-based clinical trial enrollment). For cardiovascular drug trials, only 2.5% of all trial participants were African American, again primarily attributable to non-US enrollment. 1 Thus, a paradox emerges: to address the need for more efficient and less costly clinical trials, what has transpired are trials with even less representation of real-world US populations.