Could Diversity in Clinical Trials Become Mandatory?

Initiatives by the FDA, NIH and other regulatory agencies that have urged investigators and sponsors to diversify study populations have been just that: suggestions and recommendations. But a new report by the National Academies of Sciences, Engineering and Medicine is suggesting that regulatory agencies add some bite to their guidance. The organization is recommending enforcement of diversity targets, with federal research funding as both a carrot and a stick.

While the Academies are private, volunteer, non-profit organizations, their consensus reports can have an influence in policy decision-making. The report is authored by a committee of physicians, academics, and patient advocates from a variety of prestigious medical schools, universities, and institutions.

The basis of the report is evidence that “those that often face the greatest health challenges, are less able to benefit from these discoveries because they are not adequately represented in clinical research studies.”[1] The authors recognize the progress in increasing the participation of white women in clinical trials. But it highlights the continued lack of progress among ethnic and LGBTQ communities, as well as elderly populations and those with disabilities.

As the United States continues to become more diverse, the generalizability of clinical research findings is increasingly compromised. This can influence the applicability of health screening guidelines as well as the understanding of therapeutic responses among different populations.

The report also considers health economics in its recommendations. With better outcomes, the report projects enormous economic benefits in terms of life expectancy, reduced disability, and lower health care costs overall.

Lack of diversity in clinical trials may hinder a broader understanding of biology that could benefit the general population, according to the report. A more nuanced understanding of biological processes could lead to innovation and possibly new discoveries from which everyone could benefit.

Diversifying study populations necessarily expands the pool of potential participants. Over half of all Phase I to IV clinical trials are terminated, suspended, or discontinued due to lack of accrual, according to an analysis by GlobalData. Tapping into these underrepresented populations could go a long way in addressing the stubborn challenge of lack of successful recruitment.

Creating inclusive research environments may increase trust in science and medicine. The report calls out vaccine hesitancy as an example. Efforts to persuade pregnant women to take the SARS-CoV-2 vaccine to prevent COVID-19 were stalled due the lack of data, which resulted in high levels of hesitancy among that population.

We still do not have a clear understanding of the current participation of underrepresented populations. Despite the requirement for reporting through the portal, we lack sufficient and consistent data-reporting practices. The report attempts to untangle the current situation based on a variety of methodologies.

The report also challenges the assumption that these populations do not want to participate in clinical trials, often due to historical abuses in medical research. According to the report, “the evidence on this issue is clear: Asian, Black, Latinx Americans, and American Indian/Alaska Native individuals are no less likely, and in some cases are more likely, to participate in research if they are asked.”

The report calls out variables that limit participation of these populations. The study scrutinizes individual protocol design to institutional structures, as well as study funders. Even IRBs are not spared the critical review from the authors. According to the report, “IRBs can also present barriers to diverse participation in clinical trials by limiting the types and amount of compensation given to research participants to avoid the impression of coercion or undue influence.”

The report makes a variety of recommendations aimed at addressing this critical disparity in research. Many of them have been addressed in other papers and research conferences: increasing community engagement, building trust, etc. The report strongly recommends establishing a mechanism for reporting to Congress the status of clinical trial engagement. It suggests that the FDA should require a detailed recruitment plan at the time of submission.

The report suggests incentives such as tax credits to sponsors, Fast-Track drug development opportunities, and extended market exclusivity of new drugs or devices.  Finally, the report anchors these efforts within the framework of social justice. This framing represents a paradigm shift in the thinking of diversity in clinical trials.

[1] National Academies of Sciences, Engineering, and Medicine 2022. Improving Representation in Clinical Trials and Research: Building Research Equity for Women and Underrepresented Groups. Washington, DC: The National Academies Press.