Researchers Push for Improved Racial Representation in PAH Registries, RCTs

Researchers outlined the need to combat underrepresentation of racial minorities in pulmonary arterial hypertension (PAH) registries and trials.

In a recent column published in CHEST Journal, researchers used pulmonary arterial hypertension (PAH) as an example of what rare diseases can tell us regarding disparities in disease registries, clinical trials, and treatment algorithms. As health disparities are magnified in rare disease, authors argued these instances require proactive efforts toward equitable care.

“A key mechanism of health inequity and inequality in PAH is the lack of inclusivity in national registries and in randomized clinical trial (RCT) enrollment, which form the foundations of what is known about epidemiology and treatment algorithms and effectiveness in this field,” they explained.

Minority communities are regularly underrepresented in PAH disease registries, with one national registry including 72.8% White patients, another with 85.4% White individuals, and yet another with 81.5% White patients.

“Although Black patients are reasonably represented in REVEAL Registry compared with the expected prevalence based on the 2019 US Census data (12.2% vs 13.4%), there is a noticeable underrepresentation of Hispanic (8.9% vs 18.5%) and Asian/Pacific Islander (3.3% vs 6.1%) patients,” researchers noted.

This underrepresentation in US registries poses a challenge, as most global demographic data come from American or European registries. But, however imperfect, this information is one of the only sources used to categorize PAH populations, they said.

Underrepresentation of minorities in White-dominated RCTs further calls into question the validity of evidence-based treatment guidelines, contributes to unequal access to novel therapies, and could ultimately affect patient outcomes, researchers cautioned.

In recent trials, the percentage of Black participants with PAH ranged from 0% to 21.8%, and some trials did not provide subgroup analyses based on race, socioeconomic status, or other factors.

Compounding the problem, other countries tend to look to the United States, Europe, and Australia—where the majority of trials take place—for PAH treatment guidelines. Even in multinational trials, African countries tend to be excluded.

Inconsistent demographic reporting has contributed to conflicting data regarding race and ethnicity in PAH outcomes. “Although outcomes may not be due to race per se, if we turn a blind eye to the racial breakdown of RCT enrollment, we will not be able to assure equal access to trials and their cutting-edge therapies or to interpret the generalizability of their conclusions,” researchers stressed.

One factor contributing to underrepresentation in PAH RCTs is limited access to PAH centers where trials are being conducted. Another is inherent bias among some physicians when it comes to their patients’ health literacy, financial situations, or nonadherence patterns. To combat this hurdle, authors called for an objective systematic approach to assess inclusion criteria carried out by a third-party research coordinator.

Restrictive language criteria for enrollment may also stem participation, and disenfranchised patients may be less willing to enroll. “We need to educate patients transparently about the risks and benefits of clinical trials, highlighting patient autonomy in RCT participation and implementing resources to eliminate barriers such as cost, language, and transportation,” they wrote.

To ensure generalizability of therapeutic algorithms and outcomes in PAH, attaining accurate racial and ethnic representation in registries and RCTs is crucial. Proposed steps toward this goal include:

  • Encouraging PAH centers worldwide to publish or share their patient cohorts as a step toward creating more representative national and international registries
  • Encouraging RCTs to report as many demographic identifiers as possible to disclose potential enrollment biases
  • Requiring all clinical trials, whether funded by pharmaceutical companies, the National Institutes of Health, or other granting agencies, to pledge transparency in reporting racial demographics


Goel K, Hon SM, Farber HW, George MP. Pulmonary arterial hypertension: what rare diseases tell us about disparities in disease registries, clinical trials, and treatment algorithms. Chest. Published online November 1, 2021. doi:10.1016/j.chest.2021.06.010