This story is part of a series on Diversity in Clinical Trials, which will explore the impacts of drug development using data that does not reflect the diverse U.S. population.
To read more in this series, please visit the "Diversity in Clinical Trials" Issue in Focus page here.
A woman from the Bronx, like many other young black women, does not have access to birth control, immediately eliminating her as a clinical trial participant due to risk of pregnancy — a major safety concern when testing experimental drugs.
Another clinical trial for hypertension sets the age cutoff at 50 — but African Americans tend to see earlier onset of the disease, meaning their disease is too severe to participate by that point, according to Jennifer Alvidrez of the U.S. National Institute on Minority Health and Health Disparities.
These are just two examples of how African American and black individuals can be blocked from participating in clinical trials. Patients can also be left out for not having a permanent address, or having multiple conditions, known as comorbidities.
"If a young black woman from the Bronx can't even get access to contraception, she's a no-go from the beginning," Eli Lilly and Co.'s senior adviser of clinical innovation Joseph Kim said. "It's a small example, but I'm sadly suspicious that there's probably examples like this in a lot of healthcare lenses where access to certain things immediately prevents you access to research even before you start looking for it."
The result is marketed drugs that may not accurately treat the disease population, with drugmakers at risk of facing lawsuits when minorities see unexpected — and possibly dangerous — outcomes from these drugs. Pharmaceutical companies may also be leaving patients with unmet medical needs behind.
"[Clinical trial exclusions are] actually worse than I understood before," Kim said in an interview.
'100 white men, 100 white women, 100 African American women'
A lack of basic research into conditions that primarily affect African Americans halts drug development and clinical trials before they even get started. Such is the case with sickle cell disease.
Minority Coalition for Precision Medicine founder Michael Friend compared sickle cell disease to cystic fibrosis: Despite being discovered 28 years after sickle cell, cystic fibrosis already has treatments for its symptoms and underlying cause. Cystic fibrosis, like sickle cell disease, is an inherited condition, but primarily affects white newborns.
No therapies have been approved to treat the cause of sickle cell. Just two drugs — generic chemotherapy hydroxyurea and Emmaus Medical, Inc.'s Endari — are U.S. Food and Drug Administration-approved for the symptoms, and Novartis AG's Adakveo was approved on Nov. 15 for pain associated with the disease.
A 2013 paper published in the journal Blood noted that fewer individuals in the U.S. are affected by cystic fibrosis compared to sickle cell, and yet national funding, research, new clinical trials and new drug approvals are "widely disparate" between the two conditions.
According to the American Cancer Society's 2018 report, racial and ethnic disparities in the disease burden point to the disproportionate poverty these communities face. Socioeconomic and environmental circumstances — for example, air pollution, stress levels from holding multiple jobs and access to public transportation — can significantly contribute to conditions like cardiovascular, chronic diseases and cancer.
"Racial and ethnic minorities tend to receive lower-quality healthcare than [non-Hispanic whites] even when insurance status, age, severity of disease and health status are comparable," the American Cancer Society report said.
Clinical trial recruitment is often based on a study's local demographics or the national population. The National Institute on Minority Health and Health Disparities' Alvidrez said analyzing population subgroups by the risk specific diseases pose to them is vital. Oversampling, or examining a disease impact in a higher number of minorities than is reflected in the real population, may be a better approach, according to Alvidrez.
"You may want to stratify your sample so you have 100 white men, 100 white women, 100 African American women, so on and so forth," said Alvidrez, a program official in the division of clinical and health services research. "That's not going to reflect the U.S. population, but it will meet your analytical research question. I'd say representativeness as relative to U.S. population is not necessarily the best index of what minority inclusion should be."
Us Against Alzheimer's chief of staff Jason Resendez said that because the industry tends to do what is cost-effective — clinical trials can run upward of several million dollars per phase — enrollment can be homogeneously white.
"If the people most likely to join your trial are older white men, then that's [whom] you're modeling for recruitment after," Resendez said.
A 'traditionally white' institution's dark history
Inequities in clinical research and treatment have a dark precedent in the U.S. The Tuskegee syphilis experiments, just one instance in which white American physicians exploited minority populations, deliberately left African American men untreated and uninformed for decades. The study ended 47 years ago, but for some, the wounds are still fresh.
A 2018 survey conducted by the Center for Healthy African American Men through Partnerships examining attitudes of black men and women toward genomic testing and prostate cancer testing found that the Tuskegee study was cited as a reason to stay away from healthcare institutions and research. Participants also suspected that providers receive financial gain for writing prescriptions, and had concerns about how the research is used.
Overall, the perception of healthcare as a traditionally white institution contributes to a general mistrust, according to the study. Participants said positive relationships with providers helped them make decisions about testing, and having more black providers would encourage engagement.
Only 5.7% of physicians and surgeons are black, according to 2016 data from the Census Bureau. Ayodola Anise, former senior program officer of the Patient-Centered Outcomes Research Institute's healthcare delivery and disparities research program, said racial and ethnic minorities are not reflected in research leadership.
A 2017 paper published in Health Communication reported that implicit racial bias among non-black physicians results in negative communication and negative patient experiences. Another 2007 study in the journal Cancer found that healthcare providers' attitudes and perceptions presented a barrier to minority patient enrollment in trials. Providers can make assumptions about black patients' mistrust of and general attitudes toward the medical system, whether they are even eligible for trial participation, and whether they can afford treatment.
An overarching lack of diversity among providers and medical leadership means that sometimes, black patients are not even told about clinical trial opportunities to begin with.
"The trust issue is present, but the idea that minorities may be distrustful … is actually a bigger barrier," Alvidrez said. "Clinical trials on willingness find that there isn't a difference between African Americans and non-Hispanic whites, but whites are much more likely to be approached."
Adding to the high barrier to entry is the lack of education on clinical trials.
More transparent communication and overall information, like why a study is being conducted on stage 4 breast cancer rather than breast cancer in general, would benefit both sides of the table, Minority Coalition's Friend said.
Anise said even small changes — such as saying "project" rather than "study" or "research," and asking "Do you have trouble breathing?" rather than "Do you have asthma?" — could make a big difference in clinical trials discussions with African Americans.
"A lot of people perish from lack of knowledge," Friend said. "There's no excuse for that. We have all the technology and all the knowledge … but the way the information is being shared is not really hitting the community to the extent that will cause people to respond."
What's being done
Organizations like Friend's and Anise's have had to start from scratch with minority communities due to the lack of existing infrastructure for minority recruitment.
Friend's organization, based in Baltimore, is partnering with ministries and the Health Ministries Network to disseminate information through sources the community already trusts, and encouraging minority startups. The group is also hammering out a collaboration with CRISPR Therapeutics AG, a gene-editing company developing a sickle cell disease treatment. No further details were available as of October 2019, according to a CRISPR Therapeutics representative.
The Patient-Centered Outcomes Research Institute has produced an educational video depicting African American patients to increase representation in educational materials. The group also solicited suggestions for improvement from patients before the initiation of a trial, which resulted in additional options for surveys — via phone, computer or in-person — during trials, Anise said.
"Healthcare's overall aim is to provide care to a wide and diverse population," Anise said. "The healthcare system can't be a one-size-fits-all solution."