The Future of Clinical Trials: Diversity, Transparency, and Reform

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CLINICAL REFLECTIONS

Clinical trials are vital to the development of new drugs and treatments, but they are not without controversy. In recent years, there have been several high-profile cases where clinical trials have been called into question due to issues with transparency, diversity, and other ethical concerns. One such case involved the controversial clinical trial of the drug aducanumab, which the US Food & Drug Administration (FDA) approved in 2021 despite questions about its efficacy and safety.

The aducanumab controversy has highlighted the need for greater transparency and reform in the clinical trial process. One area that requires particular attention is the lack of diversity in clinical trials. Studies have shown that clinical trials often do not reflect the demographics of the populations that will ultimately use the drug or treatment being tested.^1,2 This can result in treatments that are less effective for specific populations or that have unexpected adverse effects.

An Internal Review Reveals Need for Change

The issue of diversity in clinical trials has been a long-standing problem in the pharmaceutical industry. Historically, clinical trials have been overrepresented by white participants, which has led to drugs that are not necessarily effective for all populations.

With calls for greater diversity in clinical trials to address this issue, Pfizer conducted an in-depth analysis of its US clinical trials between 2011 and 2020. The report revealed some troubling statistics regarding the lack of diversity in clinical trials. The report found that Pfizer’s clinical trials included a diverse range of participants, with roughly equal numbers of men and women and a good representation of different age groups.³ However, the report also revealed that there were significant disparities when it came to race and ethnicity.

In particular, the report found that white participants were overrepresented in Pfizer’s clinical trials. In contrast, Black and Hispanic participants were underrepresented. For example, while white participants made up 69% of the US population during the study period, they accounted for 82% of the participants in Pfizer’s clinical trials. Meanwhile, Black participants, who made up 12% of the US population, accounted for just 5% of the participants in Pfizer’s clinical trials.⁴

However, this data needs to be analyzed based on the prevalence of the disease among different populations. There cannot be a 1-size-fits-all strategy to address the diversity problem. Some diseases such as sickle cell disease disproportionately affect African American and Asian populations compared to the Caucasian and Hispanic populations.

Pfizer's report also highlighted the need for greater diversity in clinical trials for COVID-19 vaccines and treatments. The company's clinical trials for its COVID-19 vaccine included participants from a variety of racial and ethnic backgrounds. However, much work must be done to ensure that all populations are represented in clinical trials.

The US Government Prioritizes the Issues

President Biden's Food and Drug Omnibus Reform Act of 2022 aims to address this issue by requiring pharmaceutical companies to include diverse populations in their clinical trials.⁵ The bill also includes provisions to improve the effectiveness of drugs and medical devices. The FDA has been issuing a series of guidelines and recommendations for sponsors of the Racial and Ethnic Diversity Plan (REDP), decentralized clinical trials, and related topics.

The Biden Administration has clarified that improving diversity in clinical trials is a top priority. In a statement, the administration said that clinical trials should represent the nation's diversity so that all Americans can have confidence that the treatments and vaccines they rely on are safe and effective.⁶

Ethical Concerns and Socioeconomic Barriers

There are also concerns about the ethics of conducting clinical trials in certain populations. For example, some argue that it is unethical to conduct clinical trials in certain countries or to recruit participants from populations wherein individuals may not fully understand the risks and benefits of the trial.⁷

In response to these concerns, the pharmaceutical industry and the next generation of decentralized clinical trial management software service providers are embracing regulatory and ethical guidelines as well as language support and other accessibility features to remove barriers for executing diverse clinical trials.^8,9 These guidelines emphasize the importance of informed consent, ensuring that participants fully understand the risks and benefits of the trial before deciding to participate.

In addition to increasing racial and ethnic diversity in clinical trials, removing socioeconomic barriers is important. Clinical trials often require participants to meet certain eligibility criteria, such as having a certain income level or access to transportation. These criteria can exclude people from lower socioeconomic backgrounds, who may be more likely to experience the health conditions being studied in the trial.¹⁰

To address this issue, some clinical trial sponsors have started providing transportation and other resources to help potential participants overcome socioeconomic barriers.³ For example, the National Institutes of Health (NIH) All of Us Research Program is enrolling a million American participants including from underrepresented communities in an entirely decentralized research study. The Decentralized Trials & Research Alliance (DTRA) also has formed a consortium of companies committed to advancing the meaningful adoption of decentralized clinical trials paradigm.

Concluding Thoughts

There is an urgent need for greater diversity in clinical trials. President Biden's Food and Drug Omnibus Reform Act of 2022 is a big step forward in the right direction. Still, more must be done at the investigator site level, which is where inclusion can be achieved by treating the underrepresented patients right, when they show up each time, to ensure that diversity, equity, inclusion, and access (DEIA) are truly achieved in clinical trials industry-wide.

Harsha Rajasimha, MS, PhD

Dr Rajasimha is the founder and CEO of Jeeva Informatics, a clinical trial research management software company.

References

1. Gross AS, Harry AC, Clifton CS, Della Pasqua O. Clinical trial diversity: an opportunity for improved insight into the determinants of variability in drug response. Br J Clin Pharmacol. 2022;88(6):2700-2717.

2. Loree JM, Anand S, Dasari A, et al. Disparity of race reporting and representation in clinical trials leading to cancer drug approvals from 2008 to 2018. JAMA Oncol. 2019;5(10):e191870.

3. Rottas M, Thadeio P, Simons R, et al. Demographic diversity of participants in Pfizer sponsored clinical trials in the United States. Contemp Clin Trials. 2021;106:106421.

4. Diversity in our clinical trials. Pfizer. Accessed August 23, 2023. https://www.pfizer.com/science/clinical-trials/diversity

5. 7 new FDA inspection-related policies in the Food and Drug Omnibus Reform Act. The FDA Group LLC. January 3, 2023. Accessed August 23, 2023. www.thefdagroup.com/blog/inspection-policies-food-and-drug-omnibus-reform-act

6. Sipes G, Ragan L. Preparing U.S. clinical trials infrastructure for emergencies: a White House virtual roundtable discussion. The White House. January 6, 2023. Accessed August 23, 2023. https://www.whitehouse.gov/ostp/news-updates/2023/01/06/preparing-u-s-clinical-trials-infrastructure-for-emergencies-a-white-house-virtual-roundtable-discussion/

7. Weigmann K. The ethics of global clinical trials: in developing countries, participation in clinical trials is sometimes the only way to access medical treatment. what should be done to avoid exploitation of disadvantaged populations?EMBO Rep. 2015;16(5):566-570.

8. Policies to improve clinical trial and research diversity: history and future directions. Bibbins-Domingo K, Helman A, eds. In: Improving Representation in Clinical Trials and Research: Building Research Equity for Women and Underrepresented Groups. 2017.

9. Diversity plans to improve enrollment of participants from underrepresented racial and ethnic populations in clinical trials; draft guidance for industry; availability. US Food & Drug Administration. April 2022. Accessed August 23, 2023. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/diversity-plans-improve-enrollment-participants-underrepresented-racial-and-ethnic-populations

10. Removing socioeconomic barriers and increasing diversity in clinical trials would have a positive economic impact. Cision PR Web. News release. January 3, 2023. Accessed August 23, 2023. https://www.prweb.com/releases/removing-socioeconomic-barriers-and-increasing-diversity-in-clinical-trials-would-have-a-positive-economic-impact-853116224.html