Earlier this year, U.S. Congress passed a law that requires the submission of a diversity plan for late-stage drug trials and the development of guidance to “encourage meaningful diversity among clinical trial participants, including with respect to race, ethnicity, age, sex, and geographic location, as appropriate.” This law marks a big step towards a more equitable healthcare for people who fall outside of the majority, whether based on their race/ethnicity/ancestry, geographic location, age, gender identity, sex, or other factors. However, there are many more steps from this point forward for studies and their potential participants to be successful.
Creating a successful diversity plan is more than finding a patient population from a particular race, ethnicity, or location. While the Black and Latinx communities make up 33 percent of the U.S. population, they only make up 6 percent of clinical trial participants. One of the big reasons that clinical trials have been limited in diversity in the past is that trials were performed at “reliable” study sites – typically major academic medical centers with large numbers of white patients of a higher socioeconomic status who participated with confidence in the institution and their physicians and had few systemic barriers. These are not likely to be the same institutions or physicians who have established a trusted relationship with diverse racial/ethnic minority groups in their communities.
WHY CLINICAL TRIALS ARE DOMINATED BY WHITE PATIENTS
There is not just a single reason why individuals who are part of racial/ethnic minority groups have not participated in clinical trials in the same numbers as white patients and families. We hear many terms used to describe the impact of systemic biases on minority communities including marginalized, underserved, historically excluded, etc. There are components of the truth in each of these, but individually, they don’t paint a complete picture.
Many groups, including racial and ethnic minority groups have been pushed to the margins of medical practice, including clinical trials, by the health and research systems that are meant to serve them. They have been treated as “out of sight, out of mind”. These same individuals are highly underserved, not due to their unwillingness or disinterest in participating but because they aren’t asked to participate and they aren’t given the support needed to make participation feasible.
“Historically excluded” has a particularly dark irony, as one of the frequently-cited reasons for lack of diversity in clinical trials is the historical abuses that people of color were subjected to in horrific and inexcusable experiments like the Tuskegee Syphilis Study and eugenics initiatives in North Carolina, Puerto Rico, and other states (for additional history, read our Racism in Pregnancy and Childbearing: A Path to Equal Reproductive Rights blog post). Sadly, people from racial/ethnic minority groups were excluded from beneficial trials and research efforts but coerced or forced into those that did significant damage.
In order to move forward, we can’t be satisfied by identifying and approaching people from racial/ethnic minority groups and other communities who have not been supported and enabled in clinical trials. We must address the multiple and complex barriers that keep them from participating and focus on dismantling those barriers. This is how we create equity in clinical trials – by creating a path towards participation that is as seamless and streamlined for one person as another. We also must be thoughtful about what unique factors contribute to challenges in clinical trials involving genetics.
RECRUITING DIVERSE POPULATIONS REQUIRES DIVERSITY IN GENETIC TESTING
For those of us looking at clinical trials diversity, one critical factor that cannot be ignored is that there is a direct line from disparities in genetic counseling, testing, and population genomic studies to challenges recruiting diverse populations. (See Figure 1)
Figure 1: Challenges To Expanding Diversity for Clinical Trials
It is widely accepted that people from non-European backgrounds are significantly underrepresented in biomedical research, including population genomic studies. While some large initiatives, like the All of Us Research Study, are actively working to change this, the current databases that laboratories depend on to interpret the medical significance of genetic variants are heavily skewed towards people of primarily Northern European ancestries and may not be of comparable clinical utility in all populations. As a result, people of color are much more likely to have a variant of uncertain significance (VUS) reported when they have clinical genetic testing, meaning that there is insufficient information to know if the variant is causing disease in the patient. When a patient has a VUS, even if they have clinical characteristics consistent with the genetic condition, they are generally not eligible for clinical trials. They must wait until a clinical lab has enough information to reclassify the variant as pathogenic, or causative of disease. This is a process that can take many years, dramatically limiting the ability of people of color to participate in clinical trials.
Additionally, there are clear disparities in the frequency of genetic testing in people of color compared to white patients. These disparities have been documented extensively in cancer. One highly-utilized clinical genetics lab published on more than 165,000 patients who had hereditary cancer panel testing and only 6.5 percent of the patients were African-America/Black, 6 percent were Hispanic and 4.2 percent were Asian, while 64 percent were “Caucasian” or white. Additional studies have shown that people of color are offered testing less frequently than white patients, confirming that this difference in testing is not only due to people of color “underutilizing” genetic tests but rather that they aren’t offered testing at the same rates.
IT’S TIME FOR EQUITY IN CLINICAL TRIALS
Genetically-targeted therapies are advancing and we are moving to cures rather than band-aids for patients with genetic disorders. In the past ten years, exon skipping drugs for Duchenne muscular dystrophy, protein modulator therapies for cystic fibrosis and gene therapies for spinal muscular atrophy, epidermolysis bullosa and Duchenne have changed the natural course of these diseases. To date, much of the progress has been in genetically-targeted therapies for conditions more prevalent in people of European ancestry (e.g. cystic fibrosis, spinal muscular atrophy). Once again, we are starting from a place where people of color are disadvantaged and now it’s time to change. By actively learning from past mistakes and being open to new approaches for patient/participant recruitment, engagement, and support, we have an unprecedented opportunity to embed health equity in the fabric of clinical trials and access to therapeutics so that it is never an afterthought again.
This is an optimal time for the genetics and clinical trials communities to collaborate to expand clinical trial diversity. Genome Medical is excited to partner with groups who also seek to overcome these pervasive disparities. Our Genetic Advisory Services team has helped many organizations develop and implement innovative strategies to best create equity and engagement of diverse populations in genetic testing and clinical trials. Contact us to start the conversation.
For additional blog posts about the intersection of genetics/genomics, diversity, and health visit our Genome Medical Diversity, Equity & Inclusion resources page.
About the Author: Erica Ramos, MS, CGC
Erica develops the company’s strategy, value proposition, and overall approach to population-scale initiatives utilizing genetics and genomics. Prior to joining Genome Medical, Erica focused on developing programs to accelerate the responsible adoption and integration of genomics into preventive care and population health with organizations like Geisinger Health and Illumina.