Why is it so important?
One thing that is for sure when it comes to developing new medicines or treatments is that clinical studies must be done to ensure that they work and are safe. These studies need a large volume of participants to collect accurate data. Unfortunately, most people who join a study are of a single demographic. How does this impact the results? Why is it essential to have a wide variety of people in clinical trials? What can be done to improve the number of individuals involved?
Clinical research is essential. In fact, clinical trials are indispensable when it comes to the approval of a new drug. Individuals who participate are volunteers, without whom the process wouldn’t be possible. Past thinking favored the enrolment of individuals with similar characteristics to limit variability and reach consistent short-term results. Typically, this meant drug study subjects were predominantly white males. Obviously, this isn’t an accurate representation of the patient population.
The lack of diversity impacts how well we understand the effectiveness or dangers of medicines in different groups, like women, children, and people of other ethnic or racial backgrounds. Studies have shown how well a drug works, the likelihood of side effects, and the types of side effects differ by ethnic group. In addition, standard medical advice might not be appropriate when applied to different demographics. One familiar example is original research about heart disease only looked at men, which disadvantaged women experiencing the condition because it manifests differently in them.
The most significant discrepancies occur between ethnic and racial groups. Black patients sometimes need a different dosage or drug for certain asthma, blood pressure, and heart conditions than white, Asian, or Hispanic patients with the same diagnoses. For example, a chemotherapy drug, 5-fluorouracil, has been well-studied and was found to cause adverse effects, such as hematological toxicities, in specific individuals, like Blacks. However, this wasn’t revealed in clinical trials because they had limited patient diversity. In 2014, a Clinical Pharmacology & Therapeutics study discovered variations in how people from different ethnic groups reacted to around 20% of the new drugs approved between 2008 and 2013.
Unfortunately, imbalances in the representation of minorities in clinical research aren’t new. One review of 379 clinical trials funded by the U.S. National Institute of Mental Health during 1995–2004 found that all racial or ethnic groups besides whites and Blacks were under-represented. Further, only about 48% of the studies gave complete racial or ethnic information. In a 2019 study published in JAMA Oncology, the typical cancer clinical trial was about 76% white, 18% Asian, 6% Hispanic, and 3% Black even though Black and Hispanic patients comprise 22% and 44% of the cancer incidence in the U.S.
Another problem is that 50% of Food and Drug Administration (FDA) trials in the U.S. are conducted in only 1-2% of zip codes. While massive amounts of research are being conducted, it’s happening at the same sites, in the same patient populations. Unfortunately, it means there isn’t a diverse representation within the trials.
The lack of diversity isn’t just a U.S. problem. A 2020 analysis of the global participation in clinical trials by the FDA underscored the considerable difference between enrolled participants and the global population. Of 292,537 participants in clinical trials globally, 76% were white, 11% were Asian, and only 7% were Black. In comparison, according to the World Population Review, the global population (around 7.8 billion) is distributed with roughly 60% of the population in Asia, 16% in Africa, 10% in Europe, and 8% in Latin America.
The failure to have diversity in clinical research has considerable social and ethical implications. The imbalance leads to substantial differences in lifelong care, leading to additional health inequities. The Covid-19 pandemic highlighted how these inequalities impact vulnerable populations disproportionately. A 2020 study found that 34% of overall deaths were among non-Latino Black people despite this group only accounting for 13% of the general U.S. population. The increase in disease mortality in these populations is attributed to pre-existing comorbidities (ex. hypertension or diabetes), decreased access to testing, inequities in healthcare delivery, elevated exposure risks, and genetic differences (possibly).
6 Challenge Areas
Six major challenges have been identified as reasons for reduced participation in clinical trials:
- Low income
- Investigator bias
- Mistrust in medical research and professionals
- Limited health and research literacy
- Lack of access
- Lack of benefit
Low income. Taking part in a clinical trial takes time and money. Some individuals, especially minorities, can’t afford to take time off from work or pay for the cost of traveling to the research center. In addition, sometimes, participants must pay for part of the care they receive, which is unlikely to happen for individuals in certain groups. Data shows that people with annual household incomes below $50,000 are 27% less likely to join a clinical trial. When you consider that the average household income for Black individuals is around $40,000, it’s no wonder they aren’t represented in clinical trials.
Investigator bias. Studies have demonstrated that racial or ethnic minority patients receive poorer care than white patients because of researchers’ biases. Sometimes, researchers aren’t even aware of the bias.
Lack of trust. Mistrust and skepticism of medical professionals and the healthcare system by minority groups is common due to historical abuses. A well-known example is the U.S. Public Health Service (USPHS) Syphilis Study at Tuskegee, which investigated 600 Black men for 40 years without telling them the purpose of the research or providing any treatment. Another example is Henrietta Lacks, who was treated for cervical cancer at The Johns Hopkins Hospital in Baltimore in 1951. Doctors took her cancer cells without her consent, and scientists worldwide have used them in research. Essentially, her cells were the foundation the multibillion-dollar biotechnology industry was built on, but neither she nor her family ever received any compensation or acknowledgment. Additionally, many Black people worry their genetic material might later be used against them in a criminal investigation. In most minority communities, what they know about DNA is from crime shows. It’s challenging to separate medical use of DNA from criminal use.
Lack of information. Often, minority groups aren’t aware they’re qualified to participate in studies. Typically, they rely on their doctors or other healthcare providers to tell them, but this doesn’t always happen. Another issue is that even when minorities have access to clinical trials, they receive less information and education about them.
Lack of access. Since many trials are conducted at academic hospitals where people must have health insurance to get care and individuals who are minorities are less likely to have health insurance coverage, they’re less likely to have access to trials. Also, trials often exclude people with conditions such as diabetes, high blood pressure, and kidney disease because they might affect the outcomes. These diseases are more common in minority groups.
Lack of benefit. Minority communities feel that they aren’t receiving anything from their contributions to medical research. The mindset is that they’ve been poked and prodded and are still sick. So, what’s the point of participating in studies when they don’t gain anything?
What has been done?
The National Institutes of Health (NIH) adopted a policy, the Revitalization Action of 1993, stating all federal grants for clinical research must include women and minorities. The FDA has implemented procedures to better understand the barriers to and increase the participation of more diverse participants. In 2014, the agency created a website, Drug Trials Snapshots, with information about the demographic structure of the data collected in trials of newly approved medications. In 2019, the FDA issued guidance to encourage more minority participation in clinical trials. The recommendations included widening enrollment requirements, paying for study-related expenses (ex. transportation, childcare, and hotel stays), and holding studies in community-based medical centers and clinics. The All of Us Research Program by the NIH is making efforts to increase diversity in research, with over 80% of program participants being from communities underrepresented in biomedical research and more than 50% being from minority groups. The goal is to deliver accurate medical care by considering individual differences in lifestyle, environment, and biology.
What needs to be done?
Despite the changes that have already occurred, to overcome the long-standing inequalities in healthcare and patient outcomes much more needs to be done to have diversity and inclusion in clinical research. Changes must focus on several key points: public policy, community, institutional, intrapersonal, and interpersonal.
Public policy needs to include strict requirements for the representation of diverse populations as a necessity for the approval of new drugs and devices. The best way to do this is to have provisions that research participants must reflect the population’s diversity to receive funding. The other component is developing uniform standards to collect and record variables that capture various aspects of diversity (ex. race or ethnicity, ancestry, language, religious practices, and sexual orientation).
When it comes to community, researchers need to consider the specific priorities of patients and communities affected by the condition they’re concentrating on to guarantee that the intended populations can be effectively recruited. Often, there’s the notion that minorities don’t want to participate in clinical trials. However, they simply aren’t asked. So, community means creating partnerships to foster trust and co-create strategies and solutions to promote change. These partnerships should be between academia, community, government, and industry members. The goal should be to work with the people who already have trust in these communities by providing outreach through places like churches, community events, barbershops, and beauty salons. During outreach efforts, it should be explained what a clinical trial is, what guidelines are in place to protect participants, and how the research will benefit them. Resources should be available that minimize financial costs for clinical trial participants.
Institutions are vital to developing knowledge resources specifically for communities with historical medical mistrust. For example, they can transparently provide data for drug efficacy across different populations. Further, they would acknowledge and address areas in which data doesn’t currently exist. Culturally sensitive educational materials, like images and statements from under-represented minorities, should be developed, and multimedia platforms should be used to distribute these materials.
There’s a lack of cultural competence among researchers who haven’t been exposed to working with diverse populations. So, researchers bring their own biases, whether conscious or unconscious, which is why a deeper understanding of researchers’ knowledge, beliefs, and attitudes at the intrapersonal level must be uncovered. Any known barriers should be addressed. Clinical trial staff should receive formal training on cultural humility, bias mitigation, and recruitment strategies. Without an understanding of the mistrust of the medical community and the history behind it, researchers won’t get very far in recruiting diverse patient populations for their studies.
Interpersonally, we need to improve representation across training pathways to make research and development teams more diverse. Studies indicate that people respond better to medical professionals who look like them. When the doctor is of the same race as the patient, patients convey higher levels of trust and satisfaction. On average, the visits even last longer.
Even though the medical research community is slowly realizing the need for diversity within clinical trials, there’s still a long way to go. Not only is enhancing clinical trial diversity a moral and scientific obligation, but it’s also necessary to create fair standards of care, reduce outcome disparities between populations, and achieve and uphold social equity. When we don’t have diversity in clinical trials, we risk perpetuating health equity barriers that result in health disparities. In contrast, when broad groups of people are included in clinical trials, we can be more confident in the results. If individuals who would benefit from a new therapy or medication aren’t represented in a clinical trial, can we count the results as successful?