We need incentives, not regulation, to achieve diverse clinical trials

Lack of diversity among clinical trial participants costs billions a year in early deaths and poor health. Proven economic incentives can dramatically change the picture — if the will existed to employ them.

This was the conclusion of Edith A. Perez, MD , Carlos del Rio , and me, echoing the findings of a new report that Congress requested from the National Academy of Medicine , for which we served as Committee members. (This is a modified version of our STAT First Opinion; I speak only for myself below.)

Large swaths of the U.S. population have not been adequately represented in #clinicalresearch, so researchers lack data on new discoveries that might prevent disease and extend life in many of their patients. This includes racial and ethnic minority populations, older adults, #LGTBQIA+ individuals, individuals with disabilities, and those that are pregnant, of reproductive age, or lactating.

Confidence in the safety and effectiveness of a drug can't be assured unless groups are properly represented in the research. A recent analysis of FDA drug approvals over five years found that fewer than 20% of those drugs had clinical trial data regarding treatment benefits or side effects for Black patients. Our Committee found that white women are better represented, but progress had stalled for racial and ethnic minority populations.

The report also quantified the potential benefits of having more diverse trials. Using the Future Elderly Model from the USC Schaeffer Institute , the Committee found that hundreds of billions of dollars will be lost over the next 25 years due to reduced life expectancy, shortened disability-free lives, and fewer years working among populations that are not proportionately represented in the trials.

Assuming just 1% of that burden could be alleviated through more representative trials, it would result in more than $40 billion in gains for diabetes and $60 billion for heart disease. By comparison, the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) spends about $2 billion annually on research -- demonstrating how dramatically we underinvest in innovation.

So what can we do? One option is to demand that trials be representative, either by putting up barriers at FDA or (even worse) at Centers for Medicare & Medicaid Services . However, such regulation would chill #innovation, not encourage it--thereby harming the populations we are trying to help.

A better strategy is to create more generous financial incentives.  For example, clinical trial sponsors are often limited by institutional review boards in their ability to reimburse participants. Allowing remunerating participants for lost wages, transportation costs, dependent care, and housing would help.

But bigger results can be expected if industry players are offered incentives to take action. Among its bundle of recommendations, our committee urged the FDA to study new inducements for sponsors that meet clinical trial representativeness criteria, including tax credits, fast-track eligibility, exemption from some FDA application fees, and extended market exclusivity for drugs.

The evidence demonstrates that fast-tracking drugs and extending exclusivity can really move needle.

These recommendations mirror ones included in the Orphan Drug Act of 1983, which completely changed the face of therapeutics for rare disorders. Before the ODA, millions of people were living with #rarediseases that, despite a heavy burden, attracted little research interest. The diseases were left out of the innovation pipeline, hence the term "orphan."

Inducements in the 1983 legislation led industry to develop more than 5,000 drugs that received orphan drug designation between 1983 and 2019.

How might incentives for better representation work in clinical trials? A good example is the #Alzheimer’s drug Aduhelm, which the FDA approved in 2021 but was rejected for broad coverage by Medicare and was sent back for additional, more representative trials.

Having CMS revisit safety and efficacy decisions by the FDA is classic bureaucratic overreach. Instead, Congress could create a strong incentive for more inclusive trials by guaranteeing Medicare coverage for drugs that meet standards of representation that would be designated by the FDA.

The National Academies report recommends that the Department of Health and Human Services, the FDA, the National Institutes of Health, and other federal agencies write new regulations and impose new requirements on clinical trials. Some of these might indeed help enroll in trials more participants from underserved racial and ethnic populations. But the success of the Orphan Drug Act should be clear proof that incentives are strong and effective levers for driving change in research and in fighting diseases.

Carrots, not sticks, are what is needed to overcome the stagnancy of underrepresentation in clinical research.