The majority of people with hereditary transthyretin amyloid cardiomyopathy (hATTR-CM), a serious heart condition caused by gene mutations, are of west African descent.
But the research doesn’t reflect this reality. Most clinical data is from North America and Europe. And minorities, particularly Black people, are underrepresented.
That information gap matters because it means doctors don’t have all they need to provide the best care for those hit hardest.
“We’re running all these clinical trials, and we have all these wonderful therapies, but to translate what happens in an 80-year-old Caucasian male to a 50-year-old African American female without that data just feels irresponsible,” says Nitasha Sarswat, MD, a cardiologist with special expertise in cardiac amyloidosis at University of Chicago Medicine.
From Prevention to Treatment: Unanswered Questions
Once gene carriers form hATTR-CM, “they have categorically worse outcomes, they are hospitalized more, and they die more often than wild-type patients,” says Joban Vaishnav, MD, director of the Johns Hopkins Comprehensive Amyloidosis Center in Baltimore, Maryland.
When it comes to those who carry the genetic mutation, doctors can’t predict who’ll get hATTR-CM and who won’t. Including more people of west African descent in clinical trials could change that, potentially leading to better screening guidelines and earlier detection.
And with more data on how Black patients respond to treatment, cardiologists might be able to offer tailored recommendations or have precise protocols for those whose condition doesn’t respond to first-line, or highly recommended, treatments.
Clinical trials not only stand to improve care for people currently living with hATTR-CM or its risk-raising genes, but they improve the outlook for future generations.
‘There Are Barriers All Along the Way’
A common narrative is often used to explain racial disparities in health care: Black people don’t get the same care as White people because they don’t trust doctors. But the barriers to participation in clinical trials are not created and enforced by minority patients themselves.
They start at the top.
“From the trial sponsor, to the provider, to the patient,” Vaishnav says, “there are barriers all along the way.”
Drugmaker priorities
Trial sponsors and sites may prioritize speed and efficiency over representation, especially when a clinical trial is expensive and time-sensitive. With hATTR-CM, that may mean enrolling those easiest to reach — often patients already being seen at large academic amyloid centers — instead of making a conscious effort to ensure people with the V142I variant are included.
“A trial sponsor could say, ‘We’ve enrolled 50 wild-type patients for every one V142I patient. We’re going to halt enrollment in wild-type until we increase V142I enrollment,’ but that costs more and takes more time,” Vaishnav says.
That’s why experts say diversity has to be built into trials from the start, not treated as a recruitment problem after enrollment is underway. That may mean setting enrollment goals, allowing longer recruitment periods, and choosing trial sites based not only on speed and convenience, but also on whether they can reach the patients most affected by the disease.
Well-chosen locations
Most trials are offered at major academic centers, not in rural areas or those with a considerable Black population. That means they may never learn that a study is available or they may not have a realistic way to get to the required appointments even when they are aware.
“We, as an amyloid community, need to broaden our reach into the rural South, for example, where there’s a high proportion of Black patients and a low proportion of amyloid providers,” Vaishnav says.
Urban health systems with diverse patient populations can also play an important role. Sarswat notes that University of Chicago Medicine, like other health systems with clinics in urban centers, is an attractive site for ATTR-CM trials because of its already racially diverse patient population.
Real-world understanding
Some researchers are gaining critically important knowledge about people of color with hATTR-CM through “real-world” cohorts. Rather than recruiting patients into clinical trials that require active participation, these studies observe ATTR-CM patients by tracking their medical records and demographic data over time.
Vaishnav co-authored one like this, published last year in JACC CardioOncology, that found a link between Black race, lower socioeconomic status, and higher odds of hospitalization and death from ATTR-CM.
Real-world studies like this provide valuable information, but they cannot replace the randomized controlled clinical trials required to get lifesaving medications on the market.
Unconscious bias
Doctors may present another barrier to trial participation. To start with, research suggests ATTR-CM is underdiagnosed in Black people. Only people diagnosed with the condition would be referred to clinical trials.
“They also may be less likely to be referred to an amyloid center,” Vaishnav says, which is where trials are typically held. Across medical conditions in general, doctors may not offer clinical trials to their Black patients as readily as they offer them to White patients, perhaps because they assume Black patients won’t want to participate.
Health care providers and staff involved with recruiting and enrollment need training to help eliminate unconscious bias that may prevent them from building more inclusive study cohorts. They also need to discuss clinical trials with all eligible patients in a way that is clear, respectful, and pressure-free.
“I don’t embed discussion of clinical trials in my clinic visit,” Vaishnav says. “I set aside time when there’s no pressure and we just review everything.”
Socioeconomic barriers
Even when trials are offered to Black patients, they may face other barriers to enrollment, ranging from practical and financial to cultural and emotional. From the get-go, trial participation often calls for more clinic visits than regular care. That requires transportation and time off work. Study volunteers need support to ease the burden of trial participation, whether that means free transportation, child care, or a stipend.
“Most of the clinical-trial companies or pharmaceutical companies will contract with a concierge service that helps with transportation for the patients,” Sarswat says. “And there are small gift cards, like $25, but does that make up for missing a day’s work? Probably not.”
A history of abuse
Finally, mistrust is often a factor, but it shouldn’t be treated as the only explanation, and responsibility for it should not be placed on would-be trial participants themselves.
Sarswat's referring to the notorious Tuskegee Syphilis Study, which included 399 Black men who had syphilis. The men were intentionally not offered treatment, even after it became readily available, to allow researchers to observe the natural progression of the disease. Often cited as the primary cause of medical mistrust in the Black community, the study may be the most famous case of medical abuse of minority patients, but it is not the only one. It’s part of a long history.
“We have to take the time and acknowledge that history,” Vaishnav says.
Language barriers and complicated consent forms may also turn prospective participants away. For someone who may already approach a doctor’s appointment with a healthy dose of skepticism and mistrust, one look at a consent form for a clinical trial might send them running. The forms are long, often written in legal language, and “completely overwhelming,” Vaishnav says.
Advocates for greater inclusion in clinical trials have long called for consent forms to be simplified, put into plain language and translated into patients’ native tongues.
Meet patients where they are
Experts stress the need for trial organizers to engage directly with the communities, and their trusted leaders, that are underrepresented in research. To that end, Sarswat gives talks to predominantly Black church congregations about amyloidosis, clinical trials, and genetic testing for V142I. She also presents to the National Minority Quality Forum, which brings together trusted community leaders who can take information about amyloidosis and clinical trials back to their communities.
Patients also have to know they can trust the doctors offering the clinical trial.
“Before even getting into talking about clinical trials, I get to know my patients as people, wanting them to understand that their best interest is in my heart and we are doing this for the right reasons,” Sarswat says.
“This is how science advances. This is how you can be helped. This is how you can help your loved ones and generations to come.”
Show Sources
Photo Credit: DigitalVision/Getty Images
SOURCES:
Nitasha Sarswat, MD, assistant professor of medicine, cardiology, UChicago Medicine, Chicago, Illinois.
Joban Vaishnav, MD, director, Johns Hopkins Comprehensive Amyloidosis Center, Baltimore, Maryland.
Circulation: Genomic and Precision Medicine: “Prevalence and Outcomes of p.Val142Ile Transthyretin Amyloidosis Cardiomyopathy: A Systematic Review.”
Journal of Cardiac Failure: “Should We Systematically Screen for the Amyloidogenic V142I Variant?”
Weill Cornell Medicine: “Here’s What We Know: Diversity in Clinical Trials.”
AAMC: “Clinical trials seek to fix their lack of racial mix.”
MedRxiv: “A Systematic Review of Representation in Clinical Trials for Transthyretin Associated Cardiac Amyloidosis: Where Demographics Diverge from Disease.”
JACC: CardioOncology: “Race and Socioeconomic Status Impact Diagnosis and Clinical Outcomes in Transthyretin Cardiac Amyloidosis.”
JAMA Cardiology: “Geographic Disparities in Reported US Amyloidosis Mortality From 1979 to 2015.”
Cancer Control: “Barriers to Clinical Trial Enrollment in Racial and Ethnic Minority Patients With Cancer.”
CDC: “About The Untreated Syphilis Study at Tuskegee.”
