Steps needed to include disadvantaged patients in mitral and tricuspid trials

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Ashwin Nathan

Incentives for the enrolment of patients from socieconomically disadvantaged groups, as well as targets for racial and ethnic minority patients, may be a way to ensure that clinical trials of devices for structural heart disease are more representative of the wider population, attendees of The Structural Heart Summit (TVT 2022, 8–10 June, Chicago, USA) heard.

This was among the messages delivered by Ashwin Nathan (University of Pennsylvania, Philadelphia, USA) in a presentation in which he discussed research characterising the demographics of patients taking part in clinical trials for transcatheter mitral and tricuspid valvular therapies.

“It has been well known and well established that clinical trials have not been representative of the population,” Nathan told TVT 2022 attendees during his presentation, noting that patients enrolled in clinical trials in the USA are generally found not to be representative of the country’s population at large.

A lack of representation at clinical trial level generates several problems, Nathan said, including limiting the generalisability of these trials to all segments, and limiting the access of novel, potentially life-saving therapies to underrepresented minority, and socioeconomically disadvantaged patients, he commented.

“There are several proposed barriers to representation in trials including mistrust of research enterprise, geographic and economic factors, a lack of inclusivity in trial planning, and a lack of inclusivity among investigators,” Nathan commented, considering some of the current potential barriers preventing greater inclusivity within the clinical trial arena.

Alongside colleagues at the University of Pennsylvania, Nathan sought to characterise the racial, ethnic and socioeconomic status of patients who participated in clinical trials for novel transcatheter valve therapies, compared to candidate sites that did not participate in these trials. In order to do so, the study team identified all hospitals in the USA with an active cardiac surgical programme—consisting of at least 10 cardiac surgical procedures—in 2019, using Medicare data.

The investigators identified the “trial-eligible” patient population within these centres, consisting of the Medicare beneficiaries who underwent cardiac surgery or transcatheter aortic valve implantation (TAVI). Racial and ethnic characteristics of these patients were documented using data files provided by Medicare, while socioeconomic status was characterised using mean household income for the patients based upon their zip code.

Those hospitals participating in clinical trials for novel transcatheter tricuspid and mitral valve therapies were identified using ClinicalTrials.gov. More often than not, it was larger as opposed to smaller hospitals that participated in the trials Nathan said, and these were more likely to be teaching hospitals compared to non-trial hospitals. Trial hospitals tended to be located in metropolitan areas, with just one participating hospital sited in a non-metropolitan area.

“When looking at the patient characteristics of trial versus non-trial hospitals, after adjusting for clinical characteristics as well as site characteristics, we found that patients treated at trial hospitals were wealthier than non-trial hospitals, with a median difference in household income of roughly US$5,000,” said Nathan.

However, he noted, the investigators did not see a significant difference in the proportion of Black or Hispanic patients treated in trial versus non-trial hospitals. “We found that among the candidate hospitals for clinical trials for transcatheter mitral and tricuspid valve therapies, trial hospitals took care of a more socioeconomically advantaged population than non-trial hospitals, but similar proportions of Black and Hispanic patients,” Nathan said, summarising the group’s findings.

“These data would suggest that broader inclusion of potential clinical trial sites may improve access to clinical trials in more socioeconomically disadvantaged patients, but efforts to improve access to trials to Black and Hispanic patients should focus on enhancing the enrolment efforts for these patients within existing sites,” the presenter added.

Nathan noted that current clinical trial site selection practices favour the same large sites that routinely conduct trials to meet recruitment goals and project timelines, and that the cost of participating in trials may also limit the types of sites that can participate.

“This may be hard for sites that are more rural and take care of more disadvantaged patient populations that operate within the margins,” Nathan said. “We propose that to improve diversity in socieoconomic status, we reduce the site-level financial and administrative burdens that are required for clinical trial participation […]to incentive sites caring for more socioeconomically disadvantaged patients in company-sponsored trials.”

Though the researchers found that sites participating in clinical trials were generally “enriched” with Black and Hispanic patients, Nathan commented that considering including racially and ethnically stratified targets prior to recruitment, and improving inclusivity among trial investigators, could go some way to improving racial and ethnic diversity among the trial population.

Later, during the same conference, Nathan delivered a keynote address in which he discussed perspectives on disparities in healthcare disparities in structural heart disease.

“Inequities in healthcare are, unfortunately, extremely well documented and pervasive. It is a massive problem that causes inadequate access for impoverished patients,” he said, in the opening to the address. “It is due, not only to structural racism in health, but also the intersectionality of environmental racism, issues with education, intergenerational trauma, injustice in the justice system, oppressive policies and socioeconomic inequities.”

Nathan pointed to research undertaken by he and his team, published in the journal Circulation: Cardiovascular Quality and Outcomes in 2021, looking at the inequities in the distribution of TAVI programmes among US hospital. Similar to his paper presented at TVT, this research, charted the characteristics of hospitals that had developed TAVI programmes, as well as the socioeconomic status of the patients these hospitals served.

Here Nathan and colleagues found that during the initial growth phase of TAVI programmes in the USA, hospitals serving wealthier patients were more likely to start programmes, a pattern of growth that they found has led to inequities in the dispersion of TAVI, with lower rates in poorer communities.

“What I think is happening is there is a problem with the entire diagnostic and treatment referral pathway,” said Nathan at TVT, speculating on why some of these disparities may exist.

“This is not easy. This is several weeks of work, several weeks of appointments, multiple trips and it can be very challenging due to issues of lack of referral, inadequate social support, unaffordable co-payments, difficulties in transportation, which can be an issue in rural areas, language barriers, and lack of trust in the system.

“These are all compounded by issues of race, ethnicity and socioeconomic status,” he added.

Nathan commented that work is needed across the value chain, from clinical trial coordinators, sponsors and participating sites, to ensure that trial populations include a more diverse range of patients.

“For the trials that are upcoming I think it is important to set racially, ethnically and socioeconomically targets for industry-sponsored and also non-sponsored trials as well,” he commented. “This will ensure that we provide access to these therapies, not only for issues of generalisability, but also because often these are lifesaving therapies.”


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