Demographic Diversity of Clinical Trials for Therapeutic Drug Products: A Systematic Review of Recently Published Articles, 2017-2022.

The US Food and Drug Administration (FDA) encourages the use of enrollment practices that will lead to clinical trials that reflect the population most likely to use the therapeutic product (drug or biologic), if approved. In doing so, the benefit-risk profile of the product may be assessed more completely and offer patients and their health care providers a better understanding of the drug profile and greater confidence in clinical trial results. The objective of this systematic review was to assess recent literature on the demographic diversity of clinical trial participants, describe the methods used in defining clinical trial diversity, and address knowledge gaps to enhance clinical trial diversity. Our literature search initially yielded 246 articles. After applying our eligibility criteria, we conducted a full-text review and analyzed the contents of the 28 remaining articles in our systematic review. Eleven (39%) of the 28 articles used a reference standard to compare the participation of populations in clinical trials to assess diversity. The majority of the 28 articles reported on adult participants; only 5 included pediatric populations. Most articles found that women and minority populations were underrepresented in clinical trials. Some articles proposed solutions to improve clinical trial diversity; however, several did not comment on clinical trial diversity. Despite a growing emphasis on demographic diversity in research, certain populations continue to be underrepresented in clinical trials. There is a need to standardize the definition of diversity in clinical trials. Future research into effective enrollment approaches and appropriate reference standards could improve demographic diversity.

Promoting Clinical Trial Diversity: A Highlight of Select US FDA Initiatives.

Although the population in the United States is diverse, there are disparities in healthcare outcomes in some populations, for example, based on characteristics such as race, ethnicity, sex, gender, age, socioeconomic status, and geographic location. Despite disproportionate healthcare outcomes, certain populations are frequently under-represented in clinical trials intended to support applications requesting US Food and Drug Administration (FDA) approval to market a drug or biologic. Additionally, safety and efficacy of therapeutic products may vary based on intrinsic (e.g., sex, age, race, and ethnicity) and/or extrinsic (e.g., drug interactions and medical practice) factors. Enrolling diverse populations in clinical trials can aid in addressing disparities and better inform the use of medical products in all patients who will use them upon approval. Herein, we outline a few initiatives and activities, such as policy development, regulatory review, regulatory research, and stakeholder engagement, that the FDA has undertaken to promote diversity in clinical trials, to support submission of such information in marketing applications for subgroup analyses, and to communicate information to the public.