Resource • White Paper
Patient Diversity in Clinical Research: Identifying Challenges, Opportunities, and Best Practices
Source: Darshan Dave, Senior Medical Writer, Biorasi
Introduction
Clinical research continues to evolve in its evaluation of the safety and efficacy of interventions including drugs, devices, surgeries, and diet – examining treatments to prevent diseases or diagnose them at an early stage, evaluating opportunities to improve the quality of life of patients, and also testing behavioral, social, environmental, and structural interventions (1). Although good clinical practice (GCP) measures ensure that patient participation in clinical trials complies with current regulatory standards for enrollment and engagement, certain patient populations are often not included in clinical trial recruitment even though they may react differently to the same intervention. This variability in clinical response is caused by genetic variations as well as a variety of lived experiences and living conditions; for example, women live longer, bear a greater disease burden than men, and require extra care for reproductive health and childbearing needs. Similarly, members of one racial or ethnic group may respond differently than those from another (2,3). Thus, leveraging diversity in clinical trial enrollment – focusing on individuals with a range of characteristics such as race, ethnicity, age, sex, gender identity, socioeconomic status, disability, pregnancy status, lactation status, and co-morbidity – is crucial in ensuring that medical discoveries are applicable to all populations for whom they are intended (3).
A total of 167 new molecular entities were approved by Food and Drug Administration (FDA) between 2008 and 2013, and approximately 1 in 5 of those studies noted differences in exposure, response across racial/ethnic groups, or both. For example, as reported in 2011, although African Americans and Hispanics comprised 12% and 16% of the US population, respectively, they only comprised of 5% and 1% of trial participants overall. Due to this discrepancy in patient participation, US minority groups such as these have not benefited as significantly from these developments as compared to their White counterparts (4). A lack of diversity in clinical trials can also distort the results and produce non-generalizable clinical information. Instead, clinical research that involves a varied participant pool has the potential to produce more comprehensive and reliable data. It may also expand current knowledge of racial and ethnic treatment variations, which could help reduce inequities in study outcomes (5). As a result, in November 2020, revised FDA guidance on clinical trial diversity was issued to establish greater involvement of diverse groups as a requirement for future studies.
Strategies for Enhancing Patient Diversity
Increasing clinical trial diversity in an effective, sustainable, and scalable manner remains a great opportunity and a mutual challenge for the pharmaceutical industry, academic institutions, and clinical research support organizations, such as Contract Research Organizations (CROs). Viable diversity strategies can be developed through a multi-stakeholder approach, gathering insights from patients, investigators, referring physicians, and clinical trial coordinators. Furthermore, thoughtful advance planning and an emphasis on patient-centric, culturally sensitive approaches to build trust, awareness, and ultimately participation, are necessary for recruiting appropriately diverse patient populations (2). These proactive diversity strategies include:
- Implementing the study design with patients in mind
While designing the study protocol, examine all aspects of trial planning, including clinical operations, feasibility, patient recruitment, and regulatory affairs, from the patient’s perspective. This can be accomplished by obtaining feedback from patients and patient advocates early in the process. It is important to ensure that the final study design addresses access for diverse groups that significantly reduces both the patient participation and study engagement burdens (6).
- Collaboration with community-based organizations and patient advocacy groups
Community-based organizations and patient advocacy groups play a critical role in cultivating diversity in clinical trials by identifying and addressing obstacles to participation, encouraging community involvement, and advocating for policy changes. Through collaboration with patient organizations and local communities, researchers and sponsors can enhance diversity in clinical trials, provide more representative research outcomes, and improve healthcare for all (7).
- Patient referrals as an approach to expand into target demographics
After a patient becomes involved in a trial, they often share their experience with others in their family or community network, who then may become more curious about clinical trials. Encouraging patients to speak with others and providing them with resources to describe the study and its advantages can drive further participation and awareness (8).
- Develop proactive, targeted messaging and outreach
It is critical that clinical trial content be provided to patients in a format that they can easily review, so that they are aware of the benefits and risks of the study. All study materials, such as advertisements, patient consent forms, and study content, should be in the patients’ native language and presented at an understandable reading level. (6).
- Identify and engage the right clinical sites
When reviewing potential clinical sites for a study, be sure to identify and engage with study locations that meet your diversity goals and have higher percentages of the selected demographics. This can also include staff diversity among the investigators and the study teams. For instance, during the recruitment process, participants may feel more comfortable interacting with doctors and other healthcare professionals who are part of their own racial/ethnic group (6).
FDA recommendation for Race and Ethnicity Diversity Plan
To improve clinical trial diversity, the FDA has issued several sets of guidance documentation. These recommendations address a range of subjects, including the collection and analysis of data on racial and ethnic groups, measures that enhance diversity in clinical trials, and the broadening of scientifically justified eligibility criteria to increase clinical trial participation. This guidance also focuses on diversity plans to improve enrollment of participants from underrepresented racial and ethnic populations because the lack of representation of these populations in clinical research reflects a broader issue regarding differential access to health care (9).
As per the recommendation, a diversity plan should be submitted for medical products for which an investigational new drug (IND) submission is required and/or for which clinical studies are intended to support a marketing submission under section 351(a) of the Public Health Service Act for a standalone Biologics License Application (BLA), or under 505(b)(1) or 505(b)(2) of the Federal Food, Drug, and Cosmetic Act for an NDA. A plan is also recommended for medical products that require an investigational device exemption (IDE) and/or clinical studies to support a device marketing submission, whether a premarket notification (510(k)), premarket approval (PMA) application, a De Novo classification request, or a humanitarian device exemption (HDE) application. Through these requirements, the FDA will evaluate the Race and Ethnicity Diversity Plan as an important part of the sponsor’s development program (9).
Conclusion
As the importance of diverse patient participation in clinical research continues to receive more scrutiny from regulatory organizations, clinical trial stakeholders must adapt their protocols to include the right mix of different races, ethnicities, ages, sexual orientations, and gender identities. In order to enhance diversity in clinical trial recruitment, various approaches can be implemented by sponsors, ranging from more patient-centric protocol designs to expansive clinical site networks that encompass more diverse communities. With FDA guidance measures now in place, clinical trial stakeholders need to listen closely to the voice of patient diversity across all aspects of their trial. This not only improves patients’ trust and engagement, but also results more reliable data, better patient outcomes, and improved possibilities to promote public health.
References
2. https://www.ncbi.nlm.nih.gov/books/NBK24684/
3. Clark LT, Watkins L, Piña IL, Elmer M, Akinboboye O, Gorham M, Jamerson B, McCullough C, Pierre C, Polis AB, Puckrein G, Regnante JM. Increasing Diversity in Clinical Trials: Overcoming Critical Barriers. Curr Probl Cardiol. 2019 May;44(5):148-172. doi: 10.1016/j.cpcardiol.2018.11.002. Epub 2018 Nov 9. Erratum in: Curr Probl Cardiol. 2021 Mar;46(3):100647. PMID: 30545650.
4. https://www.liebertpub.com/doi/full/10.1089/jwh.2012.3733
5. Bierer B, White S, Meloney L, Ahmed H, Strauss D, Clark L. Achiveing diversity, inclusion and equity in clinical research, guidance document. Multi regional clinical trial
6. https://www.medpace.com/wp-content/uploads/2023/03/DEI-Whitepaper011923.pdf
7. Wyer Rob, Cultivating Diversity in Clinical Trials: The Role of Patient Advocacy Groups, June 8, 2023
8. https://www.clinicalleader.com/doc/practical-ways-to-increase-diversity-in-clinical-trials-0001
