Start Early, Collaborate Often: Key Steps To More Diverse Clinical Trials

By Alekhya Pochiraju, member of TransCelerate BioPharma, and Product Development Global Operations, Genentech

Participants in clinical trials should represent the patients who are likely to have the health condition and benefit from the medical products being researched. This is often not the case. Racially and ethnically diverse populations are underrepresented in clinical trials, leading to persistent gaps between trial representation and real-world disease burden. This gap in representation is a concern as people of different ages, races, and ethnicities may react differently to certain medical products, either due to intrinsic (such as gender, race/ethnicity) or extrinsic (such as access to healthcare, socioeconomic conditions) factors. This concern is of heightened importance as the demographic landscape grows increasingly diverse.

As such, in April 2022, the FDA issued a draft guidance that has led some companies and industry at large to take a more proactive approach to the development of diversity, equity, and inclusion in clinical trials (DEICT) strategies.

Largely, efforts to improve DE&I have focused on trial enrollment criteria to ensure diverse populations. However, it is imperative to build strategies that enhance not just enrollment but participant engagement and retention as these remain a pertinent issue in underserved groups.

As part of my role in TransCelerate BioPharma’s Diversity of Participants in Clinical Trials Initiative, I have been collaborating with other R&D experts on developing tools to help the industry tackle DE&I efforts in an impactful and effective way. Building DEICT strategies is an industry wide multifarious effort and is a continuous learning process from every stakeholder involved. Success in this space will be driven by cross-industry dialogue, multi-stakeholder partnerships, and sponsors learning from each other to enable a collaborative approach to improving diversity in clinical trials.

4 Ways To Strengthen Sponsor-Site Relationships For Improved Trial Diversity

Overcoming the diversity gap in clinical trial research requires multilevel approaches and collaborative partnerships— a partnership among sponsors and sites that is rooted in patient feedback and guidance from health authorities. This allows for a development of thoughtful, proactive, and evidence-based strategies to address underrepresentation.

Sponsors should consider asking sites for suggestions on how to best connect with their diverse patient populations. TransCelerate has developed the Site Engagement and Capacity Building Considerations for Diversity, Equity and Inclusion in Clinical Trials (DEICT) resource, composed of a set of mitigation considerations designed to support efforts to sustainably partner with sites to enable the enrollment and retention of underrepresented patient populations in clinical trials. These mitigation considerations consist of perspectives from a series of stakeholder discussions and a Diversity Roundtable event and suggest approaches across different maturity levels.

The research identified four potential key mitigation considerations that sponsors may consider for a successful partnership with sites: 

1. Increase a sponsor’s capacity to build effective partnerships with community-based sites: Community-based sites may not have as much experience participating in clinical trials and could require additional training, capacity building, and other forms of support beyond what would typically be required for a well-established academic or large private site. Therefore, sponsors should work with their site-facing staff to review roles and discuss whether they should allocate additional resources that provide dedicated support to these community-based sites. 

2. Develop community engagement and sustainable partnerships to build trust: Sponsors and sites should work collaboratively to build visibility, rapport, and trust with diverse communities. To illustrate, as a collaborative approach, sponsors and sites should identify key community stakeholders (e.g., religious leaders, faith-based, and non-profit organizations, etc.), minority-serving healthcare providers, and other trusted voices who can support the understanding of healthcare needs and interests of racially and ethnically diverse communities in the site catchment area. The successful implementation of DEICT strategies will be dependent on both sites and sponsors having a shared understanding of diverse communities’ healthcare and clinical research needs. 

3. Identify site’s capacity building needs focused on site staffing: Sponsors should anticipate that sites will have multiple, overlapping capacity building needs related to the recruitment and retention of diverse underrepresented patient populations. Open two-way dialogue is essential to identify site-level DEICT barriers and potential mitigation approaches. In practice, this can mean evaluating existing site networks to understand staff capacity to recruit and retain diverse candidates or partnering with minority-serving professional societies and organizations that can support the identification of diverse candidates.

4. Identify site-level capacity building needs focused on support services: Patient-level barriers to clinical trial participation such as the need for childcare or eldercare, inflexible work schedules, and lack of translation support limit the accessibility of clinical trial research and greatly increase overall participant burden. Sponsors should proactively solicit input from sites and the diverse patients they serve to better understand the need for supplemental services that they may not be currently providing.

Prioritizing Diversity At The Start: Program & Portfolio-Level Considerations

Considering the latest draft guidance from the FDA, many sponsors are beginning to document the approach used to measure enrollment of racially and ethnically diverse patient populations in diversity implementation plans.

Clinical trials of the future should go beyond recruitment. It is heartening to see that the industry is looking at other ways to diversify trials through trial design before there is even a patient enrolled. Sponsors should consider diversity and inclusion early in the drug development lifecycle, as more inclusive trial practices are being strongly encouraged by health authorities.

This proactive approach includes earlier planning in the compound development process, deeper cross-functional collaboration and coordination, and the creation of standardized templates and SOPs to guide consistency across the company.

To address the health authorities’ call to action, TransCelerate has developed a DEICT toolkit designed to support sponsor efforts to leverage key portfolio- and program/compound-level diversity considerations to facilitate meaningful inclusion of diverse patient populations in the drug development life cycle.

At the portfolio level and during various stages of study design and conduct, sponsors can think about:

• Epidemiological Considerations: Understand patient populations impacted by the disease and whether and how disease impact varies for racial and ethnic minorities. 
• Operational Considerations: Understand site selection, site resourcing, and community and patient engagement perspectives. 
• Design Considerations:
  • Phase 1: Intentionally engage diverse populations during Phase 1 recruitment in alignment with the sponsor’s DEICT strategy for future planned studies. 
  • Phase 2: Consider site engagement, prespecified subgroup analysis, regulatory guidance, and inclusion/exclusion criteria. 
  • Phase 3: Further evaluate population-level differences in safety and efficacy.

Applying these considerations will help fulfill FDA-requested diversity plans. Implementation and availability of a diversity plan will enable the collection of more robust data to establish the safety and efficacy of investigational medical products for underrepresented diverse patient populations. 

Sponsors, sites, health authorities, and other industry stakeholders should explore creative and innovative ways to help ensure diversity among clinical trial participants. Improving clinical trial diversity can help improve health equity outcomes by enabling patient access and improving the scientific rigor. There are multiple publicly available resources from industry organizations to help clinical trials progress their DE&I efforts, including resources from TransCelerate Biopharma.

About The Author:

Alekhya Pochiraju is a senior lead in clinical operations, product development, at Genentech, where she provides clinical oncology operations expertise and advocates for health equity in clinical trials. She believes, with the future of healthcare geared towards personalized medicine, biomarkers are a critical element of cancer drug development and cancer therapeutics. Her recent talk at SCOPE US, Biomarkers & Precision Medicine USA Congress and Salesforce Women's Summit, focused on health equity disparity among minorities and people of color. Prior to joining Genentech, Alekhya worked in quality technology at Fluidigm and Sanofi-Genzyme. Alekhya holds a master's degree from Northeastern University in biotechnology.