Why Are We Still Excluding Persons With Disabilities (PWDs) In Clinical Trials?

By Richie Kahn, cofounder & COO, Canary Advisors

If clinical trials are intended to be representative of the larger population, persons with disabilities must be included in research

Clinical trials are meant to be generalizable to the broader population. In a country as diverse as the United States, it’s critically important to understand variations in drug response among different populations and ethnic groups. Despite this, people of color, the LGBTQ+ community, women, and the elderly, are all typically underrepresented in research. Further contributing to the lack of representation, more than one in four adults are living with at least one disability¹ and many of these individuals are already part of the underrepresented groups mentioned earlier.

In recent years, there’s been progress made to ensure clinical trials are diverse and representative of the general public. In April 2022, the FDA issued a draft guidance document titled “Diversity Plans to Improve Enrollment of Participants From Underrepresented Racial and Ethnic Populations in Clinical Trials.”² This document made clear that those submitting new drug applications would be required to create a diversity action plan (DAP) articulating their demographic goals for the study, rationale, and plans for success.

In late June 2024, the FDA released the long-awaited draft guidance³ on DAPs. The draft guidance applies to studies where enrollment begins 180 days or more after the final guidance is published and requires submission of a DAP for Phase 3 studies of new drugs or, as appropriate, other pivotal trials. In addition to creating a DAP for these studies, the FDA strongly encourages sponsors to create thoughtful and comprehensive strategies for ensuring diversity across the clinical development life cycle.

Less than two months later, the National Council on Disability released a report titled “The Implicit and Explicit Exclusion of People with Disabilities in Clinical Trials”⁴. The report notes that, while multiple efforts have been made in recent years to increase clinical trial diversity, persons with disabilities (PWDs) are often left out of the discussion.

Despite these substantive initiatives, study procedures themselves (like an informed consent document that has not been optimized for a screen reader or requires a wet ink signature from all participants regardless of their ability to hold a pen or sign their name) may be responsible for inadvertently narrowing the patient funnel.

Clinical trial inclusion and exclusion criteria also often contribute to the underrepresentation of PWDs. The National Council's report describes a 2022 study that reviewed nearly 100 clinical trial protocols. Persons in a variety of disability subgroups were excluded from clinical trials at staggering rates and typically without justification based on science or patient safety. Among other findings, those with psychiatric disabilities were excluded 68% of the time, those with substance use disorders were excluded 62% of the time, and those with visual impairments were excluded 34% of the time.

One concrete example comes from the Down syndrome community, a group that has frequently been excluded from clinical trial participation. Though nearly 90% of persons with Down syndrome go on to develop Alzheimer's before they turn 55, they were excluded from participation in multiple Alzheimer’s studies leading to FDA approval.⁵ How can researchers understand the safety and efficacy of Alzheimer’s drugs in this population if they weren’t enrolled in the clinical trials that led to approval?

The National Council on Disability makes a few key recommendations:⁴

• Study teams should document and explain the availability of reasonable accommodations in the body of informed consent documents.
• The FDA and NIH should work together to create clinical trial eligibility guidance that reduces subjectivity and PI bias in participant selection; broadens eligibility criteria; incorporates permissible accommodations into inclusion/exclusion criteria; recommends exclusion criteria be based in science; and recommends the inclusion of PWDs in patient advisory boards.
• The U.S. Department of Health and Human Services and Department of Justice should ensure Section 504 of the Affordable Care Act and Section 1557 of the Americans with Disabilities Act are being enforced at healthcare facilities to make programs and services accessible to PWDs.

Where Do We Go From Here?

Now that the FDA’s DAP guidance and the National Council on Disability's report have moved the conversation about clinical trial diversity and accessibility to the fore, the time is right for action. This includes hearing directly from patients about outcomes of interest and burdens and barriers to participation, considering study designs that allow for greater accessibility, and ensuring that clinical trial participation doesn’t result in unnecessary out-of-pocket costs for travel, lodging, childcare, and the like.

There are many methods for learning more about what matters most to patients, including focus groups, patient advisory boards, externally led patient-focused drug development meetings, patient listening sessions, and more. These engagements are excellent opportunities to explore what symptoms a meaningful new therapy would address, how success can be measured, and what study procedures and visit schedules might be so onerous that patients would either choose not to participate or be more likely to drop out.

Successfully incorporating patient insights into clinical trial designs can greatly increase the likelihood of designing studies that are both relevant to patient interests as well as accessible and feasible to enroll.

References:

1. Centers for Disease Control and Prevention (July 2024). Disability Impacts us All. Retrieved August 22, 2024, from https://www.cdc.gov/ncbddd/disabilityandhealth/infographic-disability-impacts-all.html.
2. U.S. Department of Health and Human Services Food and Drug Administration (April 2022). Diversity Plans to Improve Enrollment of Participants from Underrepresented Racial and Ethnic Populations in Clinical Trials Guidance for Industry. Retrieved August 22, 2024, from https://www.fda.gov/media/157635/download.
3. U.S. Department of Health and Human Services Food and Drug Administration (June 2024). Diversity Action Plans to Improve Enrollment of Participants from Underrepresented Populations in Clinical Studies Guidance for Industry. Retrieved August 22, 2024, from https://www.fda.gov/regulatory-information/search-fda-guidance-documents/diversity-action-plans-improve-enrollment-participants-underrepresented-populations-clinical-studies
4. National Council on Disability (2024, August 14). The Implicit and Explicit Exclusion of People with Disabilities in Clinical Trials. Retrieved August 22, 2024, from https://www.ncd.gov/report/the-implicit-and-explicit-exclusion-of-people-with-disabilities-in-clinical trials/
5. Armstrong, Annalee. (March 1, 2023). Alzheimer's meds are here. But for the Down syndrome community, it's still the 1980s. Retrieved August 22, 2024, from https://www.fiercebiotech.com/biotech/down-syndrome-and-alzheimers-pharma-clinical trials-safety-lecanemab.

About The Author:

Richie Kahn is a public health professional by training, clinical researcher by trade, and patient advocate by necessity. He is cofounder & COO at Canary Advisors, a patient engagement firm that works to better align clinical development with patient wants and needs.