A Crisis Year Brings Clinical Trials Face to Face with the Underserved
A Path Forward: Crisis as Catalyst for Change

OVID-19 is a catalyst for transformation of clinical research. The critical need to ensure greater diversity in clinical trial participation is more evident than ever. With increased attention paid to disparities in clinical trial study access and participation in recent COVID-19 vaccine trials and the global impact of clinical trial disruption due to the pandemic, there is increased need to rethink study inclusion and diversity – to develop creative ways to engage underserved communities and accommodate geographically diverse or disadvantaged populations (e.g., through remote trial models) to increase representation in clinical trials.

Who is Underserved?

In 2019, FDA issued a draft guidance identifying that there are a number of underserved patient groups (e.g., ethnic minorities, women, elderly, those at the extremes of weight range, individuals with organ dysfunction, those with malignancies or certain infections such as HIV, and children) who are routinely excluded from trials without sufficient clinical or scientific justification. Such exclusion limits the generalizability of clinical trial data, making it impossible to understand the diverse benefit-risk profile of a therapy across patient populations where significant genetic and/or biological differences may have a differential impact on the safety and efficacy of a treatment. This is particularly detrimental in ethnic minorities and rare disease populations where clinical trials have been historically lacking.

In an effort to increase inclusivity, FDA recommends the following key steps toward broadening clinical trial access, representation, and participation:

• Decreasing Burden for Patients: Designing studies with remote data collection, flexibility in visit windows, and adopting electronic or phone assessments. Reimbursement should also be considered to ease the financial burden of study participants.
• Adopt Enrollment and Retention Practices That Enhance Inclusiveness: Working collaboratively and directly with underserved community stakeholders (patients, caregivers, and patient advocates), incorporating feedback on trial design to address participant needs, and engaging in efforts such as: 1) holding public education and outreach (hosted by Industry, patient advocacy groups, medical associations, and other stakeholders) in neighborhoods where the target populations are heavily concentrated; and 2) holding accessible recruitment events during evenings and weekends to accommodate work and childcare schedules.
• Expanded Access: Utilizing FDA’s expanded access pathway to offer a broader range of patients with serious or immediately life-threatening conditions, treatment with an investigational drug when no comparable or satisfactory alternative therapy is available to them.

Pathways to Inclusion: Awareness, Collaboration, and Transformation

Although some underserved groups require distinctly different considerations, there is great opportunity to learn from past progress to help operationalize best practices moving forward.

1983 Orphan Drug Act

Up until the 1970s, there were roughly 70 FDA approved treatments for 7,000 rare diseases. Now there are roughly 700. While this still leaves over 6,000 rare diseases without an FDA-approved treatment, great strides in rare disease drug development are largely attributed to fundamental changes in public policy – incentives for sponsors and researchers, strong advocacy group initiatives to increase awareness in the community, and open regulatory policy collaboration have made it possible for the needs of smaller patient populations to be accommodated in clinical trials. Early successes seen from these efforts are demonstrated in the 1983 Orphan Drug Act which was championed by rare disease advocates, government officials, researchers and industry (a roadmap for advocacy initiatives during the 1980’s AIDS epidemic) in order to bring better progress to clinical trial conduct in neglected rare disease patient populations.

In an effort to improve broader clinical trial inclusivity efforts, greater attention to regulatory policy initiatives and regulatory flexibility (mirroring efforts in rare disease drug development) can be critical for increasing engagement among ethnic minorities and other underserved populations outlined in the 2019 FDA guidance. Beginning with awareness and acknowledgement, patient stakeholders, including advocates, sponsors, researchers, regulators, and lawmakers can begin to actively implement key steps to address long-entrenched issues of exclusion and promote clinical trial diversity.

Remote Trials

In the 2019 guidance, FDA also highlights the benefit of remote trial design for decreasing the study burden among the elderly, children, disabled and cognitively impaired individuals or underserved communities that have developed a general mistrust of clinical research. Greater advancement in the development of remote trial models is on the horizon in response to the COVID-19 crisis and will be beneficial for underserved patient communities long after the pandemic. Remote trials are showing that it is possible to effectively reduce patient burden (e.g., distance to a medical center becomes less of a barrier to participation, there are fewer hospital visits required) and potentially increase the likelihood of including a more representative patient population in studies. Remote trials provide opportunities for both underserved and rare disease communities where transportation to centralized sites may be a challenge or where patients are geographically dispersed. Remote trials, if more widely adopted and sustained long-term, will be transformative in value to patients, sponsors, and sites as they have the potential to increase trial efficiency and access like never before.

Addressing Needs of Minority Communities

A number of systemic obstacles have been identified that account for limited minority community participation in clinical research. However, many actions can be taken to increase minority engagement, including:

• Establishing community-based health programs at the clinical site level to foster trusted relationships in underserved communities.
• Employing trial personnel and patient liaisons that share commonalities with patients (e.g., racial and ethnically diverse staff) and are trained in culturally appropriate communication techniques to engender trust.
• Using trial sites close to patients’ homes, adopting remote trial models when possible, or arranging for reliable transportation when distance is a barrier to participation.
• Using interpreters and live on-screen captioning for Zoom or telemedicine calls to address language barriers.
• Including racially and ethnically diverse images in advertisements and other study materials to demonstrate inclusion.

Greater Diversity in Clinical Trials: Change in the Air?

Change is unlikely when there is a belief that change is impossible. It is clear that further progress is necessary to increase inclusivity in clinical trials. However, in the wake of COVID-19, there is a newfound awareness and a call to action. Patient advocates, industry partners, and regulators can continue to join forces and increase accountability and flexibility through joint policy initiatives. Diversity and inclusion can come only from sustained efforts in senior level support, substantial funding, and a commitment to building trust in underserved communities and maintaining it.