New Strategies Aim To Improve Diversity in Heart Failure Trial Enrollment

Muthiah Vaduganathan, MD, MPH

Although racial and ethnic populations have a greater burden of heart failure (HF), research suggests they are less likely to receive optimal disease-modifying therapies and are more likely to die from HF.

Despite this notable risk, Black and Hispanic populations have been poorly represented in HF clinical trials.

New strategies highlighted by the Heart Failure Collaboratory aimed to improve recruitment strategies for diverse patient populations, including methodical study design and site selection, diversification of research leadership and staff, broadening of eligibility criteria, community and patient engagement, and broad stakeholder commitment.

Study investigators, led by Muthiah Vaduganathan, MD, MPH, Brigham and Women’s Hospital Heart & Vascular Center and Harvard Medical School, focused on improving persistent gaps in trial enrollment proportional to the racial and ethnic composition of the HF population.

Barriers in HF Trial Enrollment

The study addressed the ability and willingness of patients with HF to actively participate in clinical trials is intricately tied to social determinants of health, including access to health care, education, income equality, and food security.

In Black communities, perceived barriers and risks of clinical trial research may be a potential barrier and is often related to systemic racism and bias. Other previously defined barriers in this population included mistrust, competing demands, socioeconomic factors, and lack of access to research information.

For Hispanic communities, enrollment may be complicated by differences in primary language and cultural factors, while some trials may specifically exclude non-English speaking patients.

“Diversity in clinical trials will continue to suffer until there are fundamental changes in the clinical research enterprise, including how patients are identified and recruited,” investigators wrote.

Investigators additionally noted from a US perspective, the globalization of HF clinical trials has resulted in a lower proportion of US patient representation, leading to limited diversity and relevance. From 118 HF trials between 2001 - 2016, data reporting by race and ethnicity were available in 47% of studies, while those that did report race saw increased rates of racial and ethnic minority participants from 13% to 30%.

Target Enrollment

A change in requirements for trial leadership and sponsors to individually power racial and ethnic subgroups to assess safety and efficacy may lead to unreasonably large studies, according to investigators. Even with improved representation, subgroups may still be underpowered for statistical determinations.

However, it was noted that encouraging adequate enrollment remained worthwhile to inform the generalizability of findings and to accumulate potential safety and efficacy signals to be explored in future trials.

Depending on the specific population, participants of a specific racial and ethnic background may be appropriately represented, underrepresented, or overrepresented. The participation-to-prevalence ratio is often used as an aggregate measure of representation in a trial relative to representation in the condition.

But, guideline-supported drugs and devices in HF have often been studied in global, heterogenous participant groups, making it challenging to calculate prevalence estimates. As such, investigators encouraged trials to target relative enrollment in that country consistent with the racial and ethnic makeup of the local HF population.

Both the National Institute of Health and US Food and Drug Administration (FDA) have committed efforts to support diverse trial enrollment through various federal efforts and policies, including the UNITE Initiative to address structural racism within the scientific community.

Strategies for Improved Enrollment

The strategies highlighted to improve clinical trial enrollment of underrepresented populations were centered on 3 themes, including:

• Research study design and site selection
• Patient, institution, and community engagement
• Changing the research paradigm

These overarching aims were thought to provide a greater understanding on the factors required for the successful participation of underrepresented populations in HF trials.

Study Design

A deliberate study design may be the first strategy to improve enrollment, as a broad inclusion criteria may avoid disproportional exclusion of underrepresented groups.

Overrepresented groups should intentionally be capped to ensure adequate enrollment, while other strategies may include reduced burden on patients, such as flexibility in participation hours, bilingual or multilingual staff and study materials, and alleviating barriers to trial participation, including transportation. The addition of formalized programming to train investigators of underrepresented groups may help strengthen patient engagement in the research process.

Engagement

Strategies that promote a patient’s confidence to participate in research may be essential to increasing underrepresented patient enrollment. Further, more effective ways to provide participating patients or clinics with medical treatment may increase the willingness of patients to partake in future studies.

Other ideas may include cultural and value-based competencies for the population of interest, such as faith and cultural beliefs, community clinic engagement through health fairs or discussions from research staff, and increasing the research “IQ” and support of underrepresented communities.

Research Paradigm

Investigators noted incentives at the sponsor and federal levels must be better aligned to promote diverse participant enrollment as well as a diverse research enterprise. Defining recruitment targets has been associated with higher enrollment of Black participants.

Additionally, the support of cardiovascular societal organizations may be essential to shifting the research paradigm, through increasing underrepresented researchers and trial participants. Industry sponsorship may also provide a significant role in addressing underrepresented trial leadership and recruitment and improve the chance of increasing diversity.

“In contemporary HF trials, diverse trial enrollment is not only feasible but can be efficiently achieved to improve the generalizability and translation of trial knowledge to clinical practice,” investigators wrote.

“Improving Enrollment of Underrepresented Racial and Ethnic Populations in Heart Failure Trials: A Call to Action From the Heart Failure Collaboratory,” was published in JAMA Cardiology.