Research sites struggle with patient diversity in their clinical trials, and this can have a negative impact on treatment outcomes. In 2018, African American people made up 13.4% of the U.S. population but just 5% of clinical trial participants. Hispanic people made up 18.5% of the U.S. population and only 1% of clinical trial participants, and so few clinical trials counted LGBTQ+ people that it’s unclear whether they’re well-represented or not.
If clinical trials lack diversity, researchers may not realize that new treatments are less effective—or even dangerous—for some patients. Research teams need to use community outreach, information, and technology to improve patient diversity so clinical trials can reflect the world we live in.
Why does patient diversity in clinical trials matter?
Clinical trials need to reflect the population who will actually use the treatment. Non-representative clinical trials could miss a treatment’s side effects, leaving doctors to wonder if they can safely use a drug or device on all of their patients.
1. Risk of side effects
Dr. Kelly Chibale, who advocates for diversity in clinical trials in South Africa, gives a powerful example of how drug side effects can differ between racial and ethnic groups. An antiretroviral drug to treat HIV, Efavirenz, was approved in 1998 after mainly being tested on Caucasian people.
However, it was later discovered that people of African descent had a 14.1% chance of metabolizing Efavirenz more slowly, which leads to the drug being less effective and a higher risk of overdose. Clinical researchers underestimated this risk because white people only had a 2.4% chance of metabolizing the drug more slowly.
Since around 20% of new drugs have different effects on people of different races, research sites need to test treatments on racially diverse patients.
2. Failure to reach people who need the treatment
When clinical research sites include underrepresented groups, they can ensure that treatments are tested on all people affected by a disease. For example, the vast majority of COVID-19 deaths were in people over 50, and the older people became, the higher their risk of death was. But of the COVID-19 vaccine trials started before September 2020, 61% excluded adults over 65.
The Pfizer-BioNTech vaccine did include older people, with 41% of global participants and 45% of U.S. participants 56-85 years of age. That vaccine was the first to receive full FDA approval.
Disease risk frequently varies by race and sexual orientation as well as by age. For example, Black people are more likely than white people to die from heart disease, while bisexual women are at much higher risk of cervical cancer than straight women. People at high risk of a particular disease deserve to be included in clinical trials focused on treating it.
Which patients are underrepresented?
To improve patient diversity and ensure treatments work for all patients, we need to understand which groups are often underrepresented in studies.
Black, Latinx, and Indigenous patients
FDA trial data from 2018 showed that Black and Latinx patients were badly underrepresented. A study on patient diversity in vaccine clinical trials backed up that result and demonstrated that Native American patients were underrepresented too.
White patients made up 78% of vaccine trial participants but only 60% of the population, a clear case of overrepresentation. Asian patients were accurately represented, composing 5.7% of clinical trial participants and 5.9% of the population.
By contrast, just 10.6% of patients in vaccine trials identified as Black, while 13.4% of the U.S. population did. Indigenous patients made up 0.4% of vaccine trial participants and 1.3% of the population, and Hispanic patients made up 11.6% of trial participants and 18.5% of the population, the most severe discrepancy of all.
Many clinical trials also exclude Latinx patients who speak Spanish as a first language. 13% of the U.S. population speaks Spanish at home, but the number of clinical trials that require English fluency rose from 2010-2015. Before 2010, just 1.7% of clinical trials required participants to be fluent in English—from 2010-2015, 9% of clinical trials required English fluency.
If these numbers continue to rise or hold steady, Latinx patients who are more comfortable with Spanish than English could continue to be excluded.
Patients 65 and older
The JAMA study on the demographics of vaccine trials found that patients 65 and older were underrepresented. 60% of vaccine trials didn’t include participants over the age of 65 at all, even though people over 65 are at the greatest risk for death from COVID-19 and influenza. The CDC also recommends that people over 65 receive COVID-19 and flu vaccines, so doctors need to know if new vaccines are safe and effective for that population.
In trials that allowed older participants, 12.1% of participants were 65 or over. But 16% of the U.S. population is 65+, and the Census Bureau estimates that by 2030 20% of the population will be 65+. The U.S. will soon have more people over 65 than people under 18, and they will need access to new, safe treatments.
It’s difficult to know whether LGBTQ+ patients are underrepresented in clinical trials or not, as many clinical trials don’t ask about sexual orientation or gender identity. This leads to a lack of knowledge about the health needs of LGBTQ+ patients.
62.4% of National Cancer Institute oncologists said they weren’t educated about LGB-specific health needs. This included not knowing whether LGB patients are at higher risk for skin cancer (gay and bisexual men are) and not knowing whether lesbian women need screening for HPV and cervical cancer (they do.)
Oncologists knew even less about how to serve transgender patients. Only 18.8% of NCI oncologists felt confident in their knowledge of trans-specific health needs. Doctors also screened a greater percentage of cisgender patients than transgender patients for cervical cancer (72% vs. 56%), breast cancer (65% vs 33%), and colorectal cancer (70% vs. 55%). But some trans people are at risk for cervical and breast cancer, and all trans people are at risk for colorectal cancer.
This means there’s a damaging lack of information throughout the healthcare industry: trans people are less likely to be screened for cancer, oncologists know less about treating transgender or LGB people with cancer, and many clinical trials, whether for cancer or other diseases, aren’t counting whether they’ve included LGBTQ+ people.
Patients with disabilities
Patients with disabilities have a similar problem to LGBTQ+ patients: they often aren’t counted in clinical trial demographics. However, many trials also explicitly or implicitly exclude patients with disabilities and mental illnesses from participating, even when it would be safe and feasible for them to join.
For example, one study found that children with disabilities were excluded from 90% of developmental studies. 74% of studies did not explain why these children were excluded, making it impossible to know if there was a justified medical reason behind the exclusion. In one review, 84.1% of studies failed to justify or poorly justified why they excluded people with disabilities.
Universal exclusions based on disability often don’t account for differences in types of disability. While a study may be too dangerous for a patient with a chronic heart condition, it could be safe for a patient with paraplegia. Some studies also implicitly, rather than explicitly, exclude people with disabilities. For example, one review found that 90% of studies excluded patients with intellectual disabilities, when 70% of those studies could have included them by adding simple accommodations.
Studies can implicitly exclude people with disabilities by requiring patients to drive, asking patients to fill out informed consent forms that use difficult language or small print without assistance, or setting up patient visits in spaces that aren’t wheelchair accessible. When this happens, doctors have less information about how new treatments perform in patients with specific disabilities.
How can we improve patient diversity in clinical trials?
Research sites need to increase the diversity of their clinical trials to provide safe, effective treatments to all patients. But how can clinical research teams recruit more underrepresented people?
1. Build trust between patients and researchers
In a Research America survey about clinical trial participation, 50% of Black respondents and 42% of Hispanic respondents said people chose not to participate in clinical research because of a lack of trust. Indigenous people were not counted in the survey that produced these results.
A separate study found that 61.8% of people believe doctors withhold information during clinical trials, 44% believe investigators see them as “human guinea pigs,” and 53.1% believe doctors will discriminate against them because of their race or ethnicity. These studies indicate that distrust of clinical trials or the doctors running them prevents many people from participating.
Communities of color have many reasons for this distrust of doctors and clinical trials. During the Tuskegee study from 1932-1972, doctors didn’t tell Black men that they were part of a study for syphilis and denied them effective treatments for syphilis when those became available. In 1951, Henrietta Lacks had a sample of her cells taken and used for research without her consent. Even her name was used without her consent or that of her family.
Though the FDA has since created ethical standards for clinical trials that apply to all patients, these past traumas make it very understandable that 50% of Black patients talk about a lack of trust in medical research. However, the same studies suggest strategies for combating this distrust.
In the Research America survey, 81% of Hispanic respondents and 74% of African American respondents said they would participate in a clinical trial if their doctor found one and recommended it to them. In the Community VOICES study, 40% of people said they would like to hear from a healthcare professional who shared their background.
“Being culturally aware is very important,” said Carlos Orantes, speaking at the Research Revolution session, “Designing More Diverse and Inclusive Trials.” Cultural awareness might mean employing diverse and multilingual staff at research sites, distributing materials in multiple languages, and giving patients options for how they receive information.
Since people are more likely to enroll in trials if their personal physician recommends them, clinical trial sites could recruit more patients by reaching out to neighborhood clinics, pharmacies, and doctors.
UCB has successfully employed this strategy, using technology to find areas with underserved populations and encouraging physicians in those areas to join studies. Technology can help connect those doctors to academic medical centers and study sponsors. Holding clinical trials at clinics in diverse areas with diverse staff can go a long way toward building trust.
2. Share information about trial eligibility
51% of Latinx survey respondents and 48% of Black respondents believed people don’t enroll in clinical trials because of a lack of information. 68% of African American respondents and 67% of Hispanic respondents also said their doctors had never spoken to them about medical research.
Physicians who don’t work at academic medical centers may not know what clinical trials are available to their patients, and they usually don’t have time to dig through enormous trial databases. Technology that automatically searches clinical trial databases and matches patients with trials based on their condition and the study’s eligibility criteria may help with this in the future.
Clinical trial sponsors also need to make sure they don’t inadvertently exclude patients when drafting study eligibility criteria. Though investigators have to prioritize patient safety above all else, the FDA notes that certain groups, including older adults and people with disabilities, are often excluded from trials without strong scientific justification.
By carefully considering the eligibility criteria for studies and making sure doctors have easy access to that criteria, clinical research sponsors can include more underrepresented groups in clinical trials.
3. Make trials patient-centric
The idea of patient-centric trials exploded in popularity during 2020 and 2021. “Patient-centric” trials strive to make clinical trials easier for participants by embracing flexibility. Patients may come to the research site to participate in trials, or they may submit data through their phones and check in with physicians through video calls.
Patient-centric trials can increase diversity, since people who live a long distance from clinical trial sites, work strict hours, or don’t have a car can’t always visit sites in person. 70% of the U.S. population lives more than two hours away from an academic medical center, and this prevents many older people, people with disabilities, and people with low-income jobs from participating in trials.
Some patients also prefer using a phone or computer to receive clinical trial information. 58% of Hispanic survey respondents and 53% of African American respondents said they would like to receive clinical trial information, data, and results through their smartphone. Receiving information on their phone can also help people who require more time to read informed consent forms or talk about them with loved ones.
However, as Leslie Byatt, Clinical Research Manager for NMCCA and UNMCC, pointed out on our podcast, not every patient has access to WiFi, a computer, or a phone, and some older patients may not be comfortable using technology. Those patients may prefer to have an in-person visit at a local clinic or pharmacy, which is why community outreach and flexibility are so important.
Patient-centric trials should also accommodate a range of disabilities. For example, informed consent could come in a visual or audio form, depending on the patient’s needs. Patients who can’t drive could use decentralized methods to submit data from home or visit sites closer to where they live so they can use public transportation.
Patient diversity in clinical trials: where do we go now?
Clinical trials need to recruit more Black, Indigenous, Latinx, LGBTQ+, disabled, and elderly participants to ensure new treatments will work for all of the patients who need them.
There’s no easy, one-size-fits-all solution to attracting diverse patients. But if clinical research teams engage local physicians and clinics, share information about clinical trials in areas that are historically underserved, and give patients flexible options for participating in trials, a more diverse clinical trial industry could become a reality.
For more on how to reach out to communities that are too often excluded from clinical research, check out the recording of the Research Revolution conference session, “Designing More Diverse and Inclusive Trials.”
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