While calls to diversify clinical trials have grown louder in recent years – gaining support from federal agencies such as the FDA and NIH – progress has largely stalled, according to a new report from the National Academies of Sciences, Engineering and Medicine.
Swaths of patients in racial and ethnic minority groups, as well as LGBTQIA+, pregnant and older adult populations continue to be left out of clinical trials. While some advances have been made in the last 30 years – women now account for roughly half of clinical trial participants – growth in other areas remains stagnant, according to the report, which was mandated by Congress and sponsored by the NIH.
Just look at an FDA summary report of clinical trials conducted between 2015 and 2019, the authors said. Non-Hispanic white patients made up 78% of participants, despite comprising only 61% of the population.
Those numbers are par for the course in biopharma. Of the 53 drugs approved back in 2020, white participants made up more than 80% of the trials regulators based their decisions on. Meanwhile, Black patients represented about 8% of participants, despite representing about 13% of the US population. Asian patients comprised just over 6% of clinical trial participants, while Native American patients represented less than 1%.
However, it’s difficult to compare data, because there are inconsistencies across agencies, according to author and University of California San Francisco professor Kirsten Bibbins-Domingo.
“The quality of data in this area is really poor,” she told Endpoints News. “So although we’ve had goals, we don’t know the progress towards goals because of the data [are] not there. ”
A lack of representation only compounds existing health disparities, the authors argue. It prevents certain patients from getting access to effective treatments and hinders innovation. That’s important because not all humans are the same biologically, and not everyone reacts to drugs in the same way.
Take efavirenz, for example, the antiretroviral medication used to treat and prevent HIV/AIDS sold under the brand name Sustiva. Research suggests that HIV patients of African descent are predisposed to developing neuropsychiatric side effects after taking efavirenz, due to specific CYP2B6 genetic variants that cause impaired metabolism of the drug.
There’s also the blood thinner warfarin, the authors pointed out. Given correctly, it helps prevent blood clots that can lead to strokes or pulmonary embolism. However, too much warfarin can lead to excessive bleeding. Patients’ dose requirements vary widely, depending on the presence of specific genetic variants. For example, populations with African ancestry are more likely to require higher average daily doses, while patients with Asian ancestry tend to require lower doses.
“Specifically, research has demonstrated that many groups underrepresented and excluded in clinical research can have distinct disease presentations or health circumstances that affect how they will respond to an investigational drug or therapy,” the report states.
Poor representation in clinical trials could even cost the country hundreds of billions of dollars, the authors added.
“Given the assumption that better representation in clinical trials would reduce health disparities by even a modest amount, the analysis found that achieving diverse representation in research would be worth billions of dollars in savings to the United States,” they said.
Clinical trial diversity has become a policy priority in recent years – the FDA released new draft guidance on the topic just a couple months ago – which is an important first step, the authors acknowledge. But efforts can’t end there.
The authors highlighted successful tactics for improvement, including establishing trust with the community, adopting more flexible approaches to recruitment and data collection, and ensuring diverse leadership exists at all entities involved with clinical trials, from academic centers to regulatory agencies.
The current lack of representation is not because patients don’t want to participate, Bibbins-Domingo said.
“There’s no evidence that the communities that are underrepresented systematically don’t want to participate,” she said. “There are some wonderful, beautiful, brilliant examples of investigative teams working together with community partners to achieve very high rates of participation and in studies.”
But it will also take time and money, the authors said.
“This includes expanded budgets for teams recruiting and retaining diverse participants, support to expand infrastructure for community organizations, and investments in community-based partnerships to reduce power differentials between researchers and participants,” they wrote.
They also recommended that the Department of Health and Human Services establish a task force focused on equity research, that would be charged with coordinating data collection and developing better tracking systems across federal agencies.
“Gaining a fully accurate status of the current participation of underrepresented populations in clinical trials and clinical research, and trends in participation over time, is very challenging due to insufficient data-reporting practices at a national level,” the report states.
The authors also recommend that the FDA require study sponsors to submit a recruitment plan detailing how they’ll ensure trial diversity no later than their IND or IDE submission.
Last month, in its draft guidance, the FDA called for drugmakers to submit such plans to the relevant IND application “as soon as practicable,” though definitely before they seek feedback on pivotal trials.
“There are many people who are doing really great work in this area and there are many people who have figured out strategies that work, who are committed to these types of issues,” Bibbins-Domingo said.
She added: “I think that what we would like to be able to do, and I think what the report speaks to, is to create a more enabling environment that allows researchers and participants and communities that are most affected to actually work in partnership, so that the science that we invest in in this country really has the potential to improve lives for all Americans. ”