NHC Comment Letter: Enhancing the Diversity of Clinical Trial Populations—Eligibility Criteria, Enrollment Practices, and Trial Designs—Guidance for Industry


By Maddie Mason, Associate, Policy

The U.S. Food and Drug Administration (FDA) released draft guidance for industry titled “Enhancing the Diversity of Clinical Trial Populations – Eligibility Criteria, Enrollment Practices, and Trial Designs.” The intent of the draft guidance is to encourage increased diversity in clinical trials by broadening eligibility criteria, so they better reflect underrepresented populations likely to use the drug once approved.

The National Health Council (NHC) supports the FDA’s efforts in expanding eligibility criteria in clinical trials, especially any efforts to ensure that more individuals with chronic diseases and disabilities, including comorbid conditions, can participate. The NHC is committed to ensuring that a wide range of patient voices are represented by focusing on the need for early, meaningful, and proactive patient engagement to ensure a balance between the benefits of increased participant diversity and the risk of unduly complicating clinical-trial design or delaying access to treatment improvements.

The NHC recently commented on the draft guidance. Following is an overview of our comments.

1. Clinical-trial sponsors should engage patient organizations in the design of trials.

The NHC has expressed concern in the past that the primary role of patients has been limited to their role as study subjects. We appreciate the FDA’s recent effort to enhance patient engagement throughout the entire process, and we urge them to engage patients as partners early in the clinical-trial design process.

For more information on patient engagement in drug development, check out the NHC’s comments on the FDA’s patient-focused drug development (PFDD) discussion documents related to Guidance 2: “Methods to Identify What is Important to Patients” and Guidance 3: “Selecting, Developing or Modifying Fit-for-Purpose Clinical Outcome Assessments (COAs).”

2. Representativeness in patient engagement is key.

Including patients in trial design and participation is a fundamental aspect to any effort aiming to increase clinical trial diversity. The patients, caregivers, advocates, and patient advocacy organizations engaged in clinical trial should be representative of the target population.

The NHC and participating stakeholders addressed the challenges of ensuring patient representativeness in patient engagement, and in a white paper described the six key principles with guiding recommendations and good practices.

3. Clinical-trial sponsor efforts to enroll a diverse set of participants should be condition specific.

The NHC commends the Agency for recognizing the importance of ensuring that individuals with comorbid conditions and/or at varying levels of disease severity are not excluded from clinical trial participation due to their complexity.

We agree with the FDA in that there is a fundamental difference between exclusion criteria based on factors presenting safety risks versus those designed to reduce “noise” or ensure an enriched population. Excluding a certain group of patients can lead to inaccurate results that could potentially mislead patients and providers. It is an essential first step to engage the patient community when determining when it is and when it is not appropriate to expand clinical trial enrollment beyond a narrow subpopulation.

4. We strongly support guidance provisions focused on reducing the burden of clinical-trial participation.

The NHC appreciates that the FDA recognizes the multitude of burdens that prohibit individuals from participating in clinical trials, and that they are addressing these restraints that deter diverse clinical-trial populations. The draft guidance discussed the following burdens:

Financial costs (e.g., travel, missing work);

Interference with work and other responsibilities;

Frequent visits to specific locations; and

Mistrust of clinical research among certain populations.

The NHC appreciates the FDA’s discussion of the types of accommodations and reimbursements that should be encouraged to ensure participation is feasible for all patients, as we believe sponsors should be allowed to offer a range of accommodations without fear of fraud or repercussions.
We are in strong support of the following guidance to reduce participant burden, including:

  • Providing clinical-trial sites in geographic locations with a higher concentration of racial and ethnic minority patients;
  • Incorporating diversity considerations when selecting health care providers to assist with clinical-trial recruitment;
  • Incorporating strategies for public outreach and education; and
  • Facilitating collaboration among industry, patient advocacy groups, medical associations, and other stakeholders to educate participants about clinical trial participation,

5. We appreciate the FDA’s additional considerations for clinical-trial design for rare-disease products.

The NHC agrees with the recommendations to engage patient advocacy groups in the drug development process for all diseases, but it can be especially important with rare diseases.
For rare disease treatments, flexibility in designing clinical trials is needed to ensure that people with rare diseases can participate. We support the following suggestions to sponsors that were offered in the draft guidance:

  • Re-enroll earlier-phase participants in phase three trials and
  • Consider an open-label extension study after early-phase studies to ensure that all study participants, including those that received placebo, will ultimately have access to the investigational treatment.

6. This Guidance offers clear direction without imposing overly-burdensome requirements on sponsors that could result in unintended consequences.

The NHC believes this guidance does a good job of offering clear direction on clinical trial diversity without being overly prescriptive, inhibiting innovations in trial design or delaying access by reducing efficiency.

Please read our comment letter, which offers more details on the NHC’s support of the FDA’s draft guidance.