In drug development, diversity must be extended to preclinical research
The pharmaceutical industry has long operated on a one-size-fits-all model, developing drugs primarily tested on, and thus best suited for, people of European descent. This approach ignores — and potentially harms — the billions of people of color on the planet. Lack of diversity occurs at all levels of the pharmaceutical ecosystem, from the makeup of C-suite and research staffs to participation in clinical trials. It even extends to preclinical research.
In 2015, the FDA began reporting on the representation of individuals in clinical trials, with the hope that raising awareness would drive meaningful change. This effort, however, has not yet yielded enough progress. Data from 2023 paint a stark picture of the ongoing racial disparity in clinical trials: among 4,522 people enrolled in 14 cancer drug trials, 62% were white, 23% were Asian, while only 2% were Black and 4% were Hispanic/Latino.
Take, for example, capivasertib (Truqap), made by AstraZeneca to treat HR-positive/Her2-negative breast cancer. The FDA’s 2023 approval of the drug was based on a clinical trial with 708 participants, 57.5% of whom were white of European/Caucasian descent; just 1.1% of participants were Black. That is surprising given that Black women are just as likely as white women to develop HR-positive/Her2-negative breast cancer but are much more likely to die from it.
In an effort to right this wrong, the FDA released its Diversity Action Plans draft guidance in June, outlining how pharmaceutical companies should work to increase clinical trial enrollment of populations that have historically been underrepresented in clinical studies.
But a major flaw in drug development pipelines continues to be overlooked: diversity in the preclinical risk assessments that precede human trials. These early evaluations, often based on human cell lines, help determine a drug’s safety and effectiveness. Researchers increasingly use human cell lines and miniature replicas of human organs grown in labs (organoids, spheroids, or microphysiological systems) to predict how new drug compounds might behave in humans. However, as I reported in a recent commentary in the journal Cell, the majority of human cell lines hail from donors of European descent. One landmark study published in 2019 indicated that, among the 1,000 most commonly used human cell lines in preclinical drug discovery, 62% were of European descent, 29% were of East Asian descent, 6% were of sub-Saharan African descent, and 2% were of Hispanic/Latino descent.
