Why Diverse Representation in Clinical Trials Is Critical
Looking at the past can help guide us for the future. Historically in clinical research, underrepresentation in clinical research has wrought the healthcare ecosystem of today with many issues. At the root of some of the issues is lack of gender, racial, ethnic, geographic, and socioeconomic representation in clinical trials. The impact of this lack of representation is profound; we know that many of the drugs and treatments developed and approved are not solving the very problem they should solve as effectively as they could for the very patients with the disease or condition. When examining the issues caused by underrepresentation, we can then determine why changing representation in clinical research studies is critical to achieving better health outcomes for all in the future.
Many underrepresented groups who are often excluded in clinical research can have distinct disease presentations or health circumstances that affect how they will respond to a drug or treatment. For example, the blood thinner Warfarin is a therapy developed using clinical study participants who were predominantly white with European ancestry. In time, we learned that Warfarin dose requirements vary across ethnic groups, even when adjusted for confounding factors, suggesting that genetic variation contributes to variability in dosing. Incorrect dosing can lead to an increased risk of bleeding, hospitalization, and even death.1 Further examination shows that the lack of representation may lead to a lack of access to adequate medical interventions for specific demographics. By restricting the demographics of certain populations included in clinical studies, we then sometimes restrict the use of therapeutics for certain people. Lack of representation may thus impede access to a specific therapeutic agent for those who need it most.
Diversification of clinical trial participants allows for greater exploration and innovation in medical advancements. Exploring the variation of individual treatment effects across different populations may be necessary not only to understand the variation that affects the safety and effectiveness of the treatment in the populations underrepresented in studies, but also to identify new biological processes that may lead to discoveries important for all populations.
In addition, we cannot ignore the health disparity in social costs for groups historically underrepresented in clinical trials and clinical research. Researchers now question whether underrepresented populations would have improved life expectancy, better quality of life, a life without disability or lowered long-term health issues, and lengthier time able to work if they had access to treatments that better matched their gender, race, or ethnicity.
It is also worth considering the continual issues the clinical research industry faces with study enrollment. By improving representation to increase the number of study enrollments, we would reduce inefficiency and waste caused by premature study termination. When a study fails to enroll and retain participants, we often need to learn more about the investigational intervention; however the result is that a multitude of human resources and dollars spent designing, beginning, and maintaining the study up to the point of failure has been wasted.
Distrust of the clinical research industry and medical establishment rooted in historical abuse is one of many barriers to participation in clinical studies among some populations. As recently as the 1990s, we have examples of unethical medical research involving African Americans. One such study was conducted by a highly esteemed academic institution. In this example, researchers at the prestigious U.S. university recruited African American boys into a study that hypothesized a genetic etiology of aggressive behavior. Using monetary incentives, they were able to convince parents to enroll their sons in the study. Participants were required to withdraw use from all medications (including asthma medications), follow a specific (low protein) diet, stay overnight (without parents), withhold consuming water, participate in hourly blood draws, and they were administered fenfluramine, a drug known to increase serotonin levels and suspected to be associated with aggressive behaviors. In addition to these methods, several other significant human subject violations were cited, including restricting the recruitment of Black children.2 Recent focus in the clinical research industry to improve diverse representation in clinical trials, as directed by the FDA, is committed to changing the importance of research, and medical enterprises have dedicated resources and work to regain trust and become more trustworthy partners. However, we have a long way to go to achieve the trust and levels of diversification that are truly needed.
Health disparities prevent us from achieving health equity. The disparity begins with clinical trials that do not represent all populations impacted by a disease. Diversity in clinical trials is becoming mandatory, which can make drugs and devices more widely beneficial. New FDA regulations will require sponsors to include a Diversity Action Plan (DAP) at the start of their clinical trials. For the industry, a DAP will likely require an overview of the disease/condition and the population who has it, goals for enrollment of underrepresented populations, and a plan of action to enroll and retain patients and overcome barriers to participation. Achieving health equity requires changes in the clinical research industry. We value everyone equally when we focus and continually make efforts to provide access to research to all. Further, we will achieve better health outcomes by including a diverse population of participants in clinical trials.
- Coronado, Gloria. Resendez, Jason. Frueh, Sara. “Episode 19: How Can Clinical Trials Better Reflect Society’s Diversity?” Issues in Science and Technology, National Academies of Sciences, Engineering, and Medicine Arizona State University, October 4, 2022, https://issues.org/episode-19-clinical-trials-medicine-diversity/.
- Washington HA, editor. Medical Apartheid: The dark history of medical experimentation on Black Americans from colonial times to the present. New York: Random House, Inc; 2006.