Most clinical trials do not score highly on the diversity front.
Ambitna explores who takes part in clinical trials, what barriers prevent others from doing so, and what patients, doctors, and those involved in drug approvals can do to improve on this.
Ambitna Diversity in Discoveries
Many diseases lack effective treatments, and many researchers worldwide are trying to address these unmet needs. Clinical trials form the cornerstone of new drug approvals, and without the volunteers who participate in clinical trials, this process would not be possible.
Yet, clinical trials overwhelmingly fail to represent the demographic diversity of the populations that the drugs in development aim to serve.
Black and Hispanic patients ‘consistently underrepresented’ in trials
“Black and Hispanic patients were consistently underrepresented compared with their expected proportion based on cancer incidence and mortality in the United States, whereas Asian patients appeared to be overrepresented, and white patients had enrollment that nearly matched their expected proportion,” A 2019 article in JAMA Oncology.
A 2018 Comment in Nature echoes these findings. Here, the authors collated data on trials that led to FDA approvals between 1994 and 2014. “The median percentage of African and African American participants per trial ranged from 1.8–3.5%. For Asian participants, the range was 0–7%, and for any group unspecified or not described as white, Black or Asian, it was 1.4–3.4%,” the authors write. Why is diversity important? Many factors can influence how an individual reacts to a drug. Along with age and sex, a person’s ethnic background can play a role.
A 2014 study in Clinical Pharmacology & Therapeutics found variations in how people from different ethnic groups reacted to around 20% of new drugs approved between 2008 and 2013.
“Lack of diversity in clinical trials is a moral, scientific, and medical issue. When trial participants are homogenous (e.g., primarily one gender, race/ethnicity, or age group), findings may be skewed and result in a body of clinical knowledge that is not generalizable. Cardiovascular health and outcomes vary among racial and ethnic groups,” the authors of a 2019 paper in Current Problems in Cardiology commented.
Medical News Today asked Dr. Loree to weigh in on this. “This ensures that the results of the trial are valid in all groups once the drug becomes available and is also a marker of access and equity in the health care system and society,” he told us. We also spoke to Rear Admiral (RADM) Richardae Araojo, who is the FDA Associate Commissioner for Minority Health and Director of the Office of Minority Health and Health Equity (OMHHE). “It is important for clinical trial participants to reflect the diversity of the population that is going to use the product so that sub-population data can be appropriately analyzed, and more meaningful clinical data can be communicated to the public,” RADM Araojo explained. “There are many benefits to diverse participation for researchers that extend, in a larger sense, to society. Racial and ethnic minority participation helps researchers find better treatments and better ways to fight diseases like cancer, diabetes, and heart disease, among other conditions that disproportionately impact diverse communities,” she continued. “In addition, it uncovers differences by race and ethnicity that may be important for the safe and effective use of therapies.” ‘Multifactorial’ barriers While there may be a will on the part of researchers and those involved in approving new drugs to improve the diversity of future clinical trials, they will have to consider many important barriers. “There are many different reasons why minorities have been under-represented in clinical trials. One barrier to participation that we all know well is a lack of trust because of past historical abuses,” RADM Araojo told MNT. “Other barriers to participation may differ based on the population you are seeking to enroll and may include language and cultural differences, health literacy, religion, and a lack of awareness and knowledge about what a clinical trial is and what it means to participate.” “Some barriers may be due to aspects of the trial design such as inadequate recruitment and retention efforts, accessibility to the site location, frequency of study visits, transportation, participation may conflict with caregiver or family responsibilities, and may cause time away from jobs and other commitments. Often times, there may be a perception that minorities do not want to participate, and they simply aren’t asked.” – RADM Richardae Araojo For Dr. Loree, health inequity is a major factor that prevents some people from participating in clinical trials. “The barriers to participation are multifactorial, however equity in access to health care is an important determinant,” he said. “Costs for participating in clinical trials include direct health care costs (i.e., imaging, supportive medications, etc.) which may or may not be covered by a person’s insurance plan and also indirect costs such as the ability of a person to travel or have a caregiver take time off from work. “These economic barriers have been shown to be major barriers to participation and impact minority groups disproportionately. There has been a move to improve the coverage of clinical trial costs among insurance plans in the United States, but economic barriers still exist for many, and those indirect costs I mentioned are not covered,” he continued. Who can drive long lasting change? “I think one of the best things physicians can do to address [the] disparity in trial accrual is to get to know their patients’ perceptions and social determinants of health. We need to listen to our patients and understand how they feel about research and the barriers each patient faces,” Dr. Loree told MNT. But doctors are not the only ones who can strive for more diversity in clinical trials. “Another important aspect is including the patient voice during the planning of clinical trials. Research groups are increasingly incorporating patient advocates during all stages of research,” Dr. Loree pointed out. “Patients have a wealth of experience to contribute to making sure research is feasible for patients and also addresses questions that are important to them.” Dr. Raghav meanwhile suggests how patients themselves can influence the demographics of future trials. “Clinical trials form benchmarks for future standards of care. All patients with cancer should regularly inquire about their possibilities of participating in clinical trials from their oncologists through the course of their treatment,” he told us. “Hav[ing] this opportunity will benefit patients, progress in combating cancer, and allow for better representation.” RADM Araojo calls for a multi-disciplinary effort. This should ideally include involving patients in how researchers design and run trials, and in developing strategies to reach diverse patient populations. “There is not a one size fits all approach to overcoming all the barriers to recruiting diverse participants in clinical trials, and there may be specific considerations for various populations that you are intending to recruit,” she told MNT. She suggested that the location of a study site is important in more ways than just the logistics of access. “Site locations where there are more racial and ethnic minorities and diverse study team staff are also efforts that support recruiting minority populations,” she explained. “A plan to address inclusion should be developed early on, should not be an afterthought, and begins and ends with the patient in mind. Consistent and continued community engagement through working with cultural ambassadors, faith-based organizations, and with trusted leaders in the community are examples of efforts that have helped support diversity in clinical trials,” she continued. What can the FDA do? RADM Araojo responded to what the FDA are doing to address the barriers that prevent diversity in clinical trials.
“FDA is committed to encouraging diverse participation in research used to support marketing applications for regulated medical products. The Agency has continued its ongoing efforts to support diverse participation in clinical trials through hosting public meetings, developing tools, and issuing guidance documents,” she explained. “Over the past few decades, FDA policy initiatives have focused on promoting enrollment practices that lead to clinical trials better reflecting the population most likely to use the product if the product is approved.”
We also asked her about the work that her office are doing. She told us this:
“In addition, the FDA’s Office of Minority Health and Health Equity (OMHHE) continues to work to advance racial and ethnic minority participation in clinical trials through a variety of culturally and linguistically competent strategies and resources, including an ongoing campaign to raise awareness on the need for racial and ethnic minority groups to participate in clinical trials.”
The OMHHE have a number of strategies, including educational material, public service announcements, and social media programs in English and Spanish. Also, there is outreach to diverse communities and healthcare professionals and collaborations across industry, academia, and the government with the aim to raise awareness about the need for more diversity in clinical trials.
“Despite these efforts, challenges to participation in clinical trials remain, and certain groups continue to be unnecessarily underrepresented in many clinical trials. The FDA continue to recommend and work with drug sponsors on approaches that will increase enrollment of underrepresented populations in their clinical trials,” RADM Araojo noted.
“As clinical trials continue to modernize and evolve, it offers new opportunities to reach diverse populations that we may not have reached in the past. So, a multisector approach, partnerships, engaging patients and providers, and sharing of best practices are opportunities to continue to advance racial and ethnic minority inclusion in clinical trials.” – RADM Richardae Araojo