May 20, 2018
A Closer Look Into the Lack of Diversity in Clinical Trials
by Fatuma-ayaan rinderknecht
When I started my position as a clinical research coordinator, working to recruit and consent patients for clinical trials, I immediately noticed how few minorities were enrolled in these trials. As a black woman, the lack of diversity in clinical trials was particularly troubling. I wanted to know more about this issue, to see if it is a systemic problem, and to better understand the effect that a lack of diversity has on clinical trials.
In considering why there might an under-representation of African-Americans in clinical trials, the first thing I thought of was the black community’s disturbing history with medical research. There has been long-standing and justified mistrust of medicine among African Americans. Most of the American public is familiar with the horrific Tuskegee Syphilis experiments, in which the U.S. Public Health Service knowingly infected unsuspecting black men with syphilis and withheld treatment from them. But Tuskegee serves as just one example of the countless injustices the black community has faced- they have served as guinea pigs for often unethical and harmful medical experiments since their arrival in North America, and throughout the 20th century. This historical mistreatment and ensuing mistrust of the medical field among African Americans has often been touted as the major reason explaining their consistently low participation clinical trials. The exceptionally low number of minorities and women in clinical trials led to the creation of the NIH Revitalization Act of 1993, meant to increase the opportunities that women and minorities had to participate in clinical trials. This Act was bolstered by the 21st Century Cures Act enacted in December 2016, which mandates that researchers conducting NIH-funded clinical trials must submit the results of the analysis of the differential impact of a particular trial on racial and ethnic minorities and women to www.clinicaltrials.gov. The law also requires that NIH examine data on the inclusion of racial and ethnic minorities and women in clinical research and investigate scientific opportunities to reduce health disparities.
Still, the participation rates of black Americans in clinical trials remains low. The FDA estimated that in 2015, African Americans made up 14.5% of clinical trials participants in the US. It is important to note that there are conflicting reports noting the percent of African Americans in clinical trials, with numbers ranging from 10% to14%. This number generally mirrors the U.S. population, which is roughly 13% black. Upon initially viewing these statistics, it may seem that the NIH Revitalization Act and the 21st Century Cures Act have been successful in improving rates of African American participation in clinical trials.
However, peer-reviewed research reveals that African Americans and other minorities are grossly overrepresented in phase 1 trials, and extremely underrepresented in phase 3 trials.
What does this mean?
Phase 1 clinical trials are meant as “safety studies”: they are the initial trials meant to generate data on the safety of a drug and the adverse events it may cause. These studies are generally done by using healthy volunteers who often receive no direct health benefit by their participation, and generally compensate volunteers at a higher rate than phase 3 trials. Drug companies are able to entice healthy participants of lower socioeconomic status to participate in phase 1 trials due to their high compensation. Phase 3 trials are done by recruiting volunteers who actually have a specific disease or condition and are performed to check for efficacy of the drug. If the drug is successful in a phase 3 trial, then the next step is moving on to FDA approval. While Phase 3 studies have the potential to actually be beneficial to participants, they are less likely to offer high compensation or other enticements to bring in poorer volunteers. “Anecdotal evidence has shown that while blacks and Hispanics make up 13% and 16% of the US population, evidence has estimated that these groups make up roughly 40% of healthy volunteers in phase I trials.”1 These numbers provide a stark contrast when compared to African American participation in phase 3 therapeutic trials. This evidence would suggest that minority patients take on much of the burden of clinical trials without reaping reward.
Not only is this an issue in terms of health equity, but it is simply bad science. Low numbers of minorities in later phase clinical trials jeopardize the effectiveness of the drug if it is eventually approved. Ethnicity and race can serve as mechanisms for genetic differences, which can cause certain populations to respond to drugs differently. Testing drugs on predominantly white populations can detrimentally affect the generalizability of that drug. A 2015 study done at UC San Francisco found that “only 2 percent of cancer studies and less than 5 percent of pulmonary studies have studied enough minorities to provide useful information,” meaning that there are very few of these drugs that have been properly tested on minority populations.
This is not a “hypothetical” issue. In the early 2000s, a blood thinner, Plavix, was found to act essentially as a placebo in a majority of Pacific Islanders as the members of population typically don’t produce an enzyme necessary for processing the drug. This oversight likely occurred because there were not significant numbers of Pacific Islanders included in Plavix clinical trials. Mistakes like these not only cause grave side effects, but also cost millions of dollars in preventable medical care. In order to produce reliable and generalizable results in clinical trials and to ensure that drugs are effective across populations, it is imperative that significant number of minorities are included in all phases of clinical trials.
When discussing low numbers of African Americans and other minorities in the later stages of clinical trials, many bring up “barriers to participation,” which include lack of access to health insurance or health facilities, as well as the aforementioned distrust of medical professionals. In looking at the numbers of minorities who serve as healthy volunteers in early stage trials, it seems that these barriers may be overemphasized when discussing minority participation rates in clinical trials.
There are several complex factors that affect minority participation in clinical trials. One important factor to consider is the underrepresentation of minorities among researchers who are conducting clinical trials. Black scientists who apply for research funding are often less likely to gain funding than their white counterparts, and it is important to note that the NIH review board that decides who gets funding is almost 90% white2. In order to recruit a diverse population, it is necessary to have diverse research and administrative staff who will understand the importance of integrating minorities in clinical trials. Patients often feel more comfortable when there are people on the staff who they can relate to. Increasing the number of minorities in these positions will help improve diversity in clinical trials down the line.
Some studies have also suggested that non-minority staff may “avoid” lower-income minorities in later phase trials because they fear poor compliance with protocol. This suggests that training in cultural competency, coupled with emphasis on recruiting minorities to trials, would be extremely valuable to NIH-funded clinical trial teams.
The representation of minorities in clinical trials continues to be a major issue; however, both Congress, government agencies, non-profits, and even some pharmaceutical companies have been working to improve on this issue. In fall of 2017, the NIH National Institute of Minority Health and Health Disparities designated 82 million dollars of congressionally-appropriated funding towards specialized research centers in order to continue and improve upon health disparities research. These centers of excellence on minority health and health disparities were mandated by the 21st Century Cures Act.
In 2014, the Pharmaceutical Research and Manufacturers of America (PhRMA) teamed up the National Minority Quality Forum to create the “I’m In” campaign, which focuses on engaging underrepresented minorities in order to increase their representation in clinical trials. While these are critical interventions, it is important to hold these organizations accountable. Although this program was launched in 2014, it was difficult for me to find data on the results or outcomes of the campaign.
For those working in the policy, research, or healthcare fields, it continues to be imperative to strive for appropriate racial representation in clinical trials. We must do so or risk creating more severe racial health disparities.
To learn more about diversity in clinical trials:
Fatuma-Ayaan is a graduate of Harvard College, and currently works as a clinical research specialist in the Pediatric Cardiology Department of UCSF.
1. Fisher, J. A., & Kalbaugh, C. A. (2011). Challenging Assumptions About Minority Participation in US Clinical Research. American Journal of Public Health, 101(12), 2217–2222.
2. Oh, S. S. et al. (2015). Diversity in Clinical and Biomedical Research: A Promise Yet to Be Fulfilled. PLoS Medicine, 12(12), e1001918.