The Slow Walking of Diversity in Clinical Trials
A recent article in STAT led with the following alarming headline:
“[National Institutes of Health] wanted to make cancer research more diverse. The effort turned out to be a costly failure.”
This headline encapsulates one of the primary arguments many pharmaceutical companies make behind closed doors—that the cost of ensuring diversity in clinical trials is higher than any potential rewards. At least, it is how this issue is perceived in some circles.
So, what made this effort from the National Institutes of Health (NIH) a ‘costly failure’? According to the spokesperson quoted in the article, it came down to two factors:
1. The National Cancer Institute’s (NCI’s) Center for Cancer Research (CCR) experienced a 45% increase in travel costs, and;
2. The program did not result in an increase in the diversity of enrollees.
What apparently made the pilot program too costly was the increased expense of providing potential patients, and in some cases, their caregivers, with funds to cover first-visit travel expenses to determine their eligibility for NCI cancer trials.
Prior to this pilot program, patients and caregivers were required to pay for travel, food, lodging, childcare, and missed work expenses out of pocket, which researchers believed would discourage lower-income patients from volunteering for trials. The thinking was that, because the populations that are disproportionately impacted by cancer health outcomes were more likely to be Black, Indigenous, and other People of Color (BIPOC) who are more likely to have lower incomes.
The NCI CCR pilot program came on the heels of a late-2022 law passed by Congress, the Food and Drug Omnibus Reform Act of 2022 (FDORA), which required pharmaceutical and medical device companies to deliver their plans for diversifying clinical trials to the U.S. Food and Drug Administration (FDA) by the end of March 2025.
This is where the issue of cost again comes into play:
Pharmaceutical and medical device companies essentially operate on a cycle that revolves around developing new products, updating existing products, and either limiting or increasing the supplies of existing and newer products on the market to ensure profitability. In order to maintain profitability, this cycle must be perpetuated to ensure that consumers, including both patients and providers, remain customers by bringing new or improved products to the market on a regular basis. This requires making products as quickly and as efficiently as possible to both control costs and increase profit margins.
The trial phases of these products can play a vital role in determining that profitability. In 2023, a pharmaceutical executive posed this question about new HIV drugs: “Are you comfortable with adding another three to five years of product development to ensure that the trials have the requisite diversity?”
When new requirements demanding diversity in clinical trials go into effect, there are significant concerns that the FDA will be heavy-handed in enforcing compliance with FDORA regulatory requirements:
“Bethany Hills, a partner at DLA Piper who represents drugmakers, said it will be difficult for FDA to strike a balance that enables researchers to notice when a drug doesn’t work for one group of people without delaying its availability to those for whom it does work” (Wilkerson, 2023).
Part of the issue is that the FDA has not yet released those regulatory requirements, so these industries aren’t even sure with what they’ll be required to comply. While the FDA is very likely to focus heavily on racial and ethnic diversity requirements, additional demographic categories may be considered, such as age, sex, and income (though the latter is less likely).
The other part of the issue is the perception that, again according to Hill, “There’s just certain populations where it’s going to be really hard to reach them.”
There are common arguments made by these industries: that it’s just too hard to make clinical trials diverse because it will take too long, because minority patients are less likely to participate, and because fewer minority patients will qualify, so they expend more resources trying to recruit diverse patient populations.
There are some data to back up these assertions:
According to October 2023 research released by Research America:
Black (69%), Asian (62%), and Hispanic patients (70%) are less likely to report that they’ve heard about a clinical trial opportunity;
While 67% of all patients surveyed reported “very or somewhat positive” feelings about clinical trials, just 57% of Black and 61% of Asian Americans responded in that manner;
Black and Asian Americans were less likely to respond that they agreed or strongly agreed that “people like me benefit from clinical research and its findings,” and;
Black Americans were less likely to agree that clinical trials were conducted ethically or that it was conducted fairly (Research America, 2023).
In addition to those findings, research from the BECOME Research Project found that, while interest and willingness to participate in clinical trials was high among Black Women, healthcare providers were unlikely to initiate discussions about clinical trials with them (Felder, 2022).
Making the matter more complex for industry manufacturers is that a majority of Americans (43%) believe that “…the FDA should act more slowly in order to reduce risk, even if it means patients may wait for treatments,” and 48% of Black patients responded in that manner (Research America, 2023).
This seems to answer the question that was posed in 2023: yes—Americans would be okay with adding three to five years to make sure that a drug works for every patient population.
These sentiments are not, of course, universal. Patients living with conditions for which there are a variety of existing medications that are relatively easily tolerated are more likely to respond that they’re willing to wait, while patients living with rare conditions for which there are few existing treatments or treatments that are hard to tolerate are more likely to respond that the FDA should speed up the process, even if it means accepting more risk.
As with patient sentiments being diverse, so too are existing pharmaceutical company commitments to ensure patient diversity in clinical trials. Rather than slow walking the march to diversity or making promises but providing little evidence of those promises’ fruition, Gilead Sciences (one of PlusInc’s corporate sponsors) has actively been recruiting diverse patient populations. According to a recent stakeholder announcement:
“The Phase 2 studies, PURPOSE 3 (HPTN-102, NCT06101329) and PURPOSE 4 (HPTN-103, NCT06101342), are part of Gilead's PURPOSE program. The PURPOSE program, which also includes two ongoing Phase 3 clinical trials, is assessing the potential of twice-yearly subcutaneous injections of lenacapavir to help a diverse range of people around the world who could benefit from HIV-1 pre-exposure prophylaxis (PrEP). PURPOSE 3/HPTN-102 is enrolling cisgender women in the U.S. who are disproportionately affected by HIV, with a focus on Black women and other women of color. PURPOSE 4/HPTN-103 is enrolling people in the U.S. who inject drugs.”
Gilead Sciences is no stranger to challenges when it comes to a lack of diversity in clinical trials for HIV prevention. In 2019, Gilead’s oral regimen for the prevention of HIV, Descovy (emtricitabine/tenofovir alafenamide) received FDA approval for use in HIV-1 Pre-Exposure Prophylaxis (PrEP) treatment in patients “…excluding those who have receptive vaginal sex” (FDA, 2019).
At the time, Gilead claimed that it would have required “…too many resources” to enroll a sufficient number of cisgender women into the trial and closely monitor their adherence to the daily pill regimen (Blackstock, 2019). Since then, Gilead has made significant strides to change its paradigm after the Descovy incident, which is laudable considering that many other companies continue to slow walk diversity efforts.
PlusInc will continue to monitor diversity issues in the clinical trial space.