linical trials do not yet adequately reflect the populations who use the drugs once they are approved. This article introduces four challenges that could slow down progress in clinical trial representation.

FDA has worked to improve clinical trial representation and has issued three final documents.

• Collection of Race and Ethnicity Data in Clinical Trials (October 2016)
• Evaluation and Reporting of Age-, Race-, and Ethnicity-Specific Data in Medical Device Clinical Studies (September 2017)
• Enhancing the Diversity of Clinical Trial Populations — Eligibility Criteria, Enrollment Practices, and Trial Designs (November 2020).

In addition, FDA published the draft guidance Diversity Plans to Improve Enrollment of Participants from Underrepresented Racial and Ethnic Populations in Clinical Trials in April 2022. In December 2022, Congress passed the Food and Drug Omnibus Reform Act (FDORA), requiring sponsors to submit plans and required FDA to update guidance on Diversity Plans by December 2023 (see Sec. 3602). FDA published an updated draft guideline on June 26, 2024.

Many questions remain. Because of the variety of diseases and patient populations, FDA might not be able to publish a plan template. Some companies have submitted Diversity Action Plans (DAP), as is now mandated by US Law. Others have begun diversity planning efforts. Not surprisingly, others are waiting and watching.

This has led to a patchwork of expectations, attitudes, and solutions for implementation in the clinical trial ecosystem. It has also revealed key issues, which could present further obstacles for diversity, equity, and inclusion (DEI). On the other hand, these issues may also present opportunities to improve the ecosystem overall.

William Bridges, in Managing Transitions: Making Sense of Life’s Changes, speaks of the “neutral zone,” or what others might call the “muddy middle.” It is a place where “forward motion seems to stop while you hang suspended between was and will be.” He describes the neutral zone as treacherous, inevitable, and also as a time of great creativity.

We identified four areas that have come into focus as clinical trial partners (sponsors, Contract or Clinical Research Organizations (CROs), vendors, sites, and communities) and regulators wrestle with Diversity Action Plans:

Misalignment

Experts in the field have observed that organizations may interpret the intent of DAP in widely divergent ways.

Operational Inertia

Industry values ways to move faster and contain costs, and diversity efforts are inaccurately characterized as delays or added expenses.

Barriers to Collaboration

Today, sponsors partner with CROs and other vendors.

Each stakeholder is struggling to figure out what role they play and how to collaborate with others, who may be shifting their own understanding.

DEI Fatigue

A major impediment to systemic change is the environment in which that change is happening. For over 400 years, American society has struggled to live up to the ideal that all are created equal.

In Conclusion

We need to change the conversation from DEI to representative clinical trials. The fundamental issue is that nobody yet knows how DAPs will affect the drug development ecosystem. The impact will need to be learned through myriad experiments, prototypes, and maybe even failures.

In this issue of DIA Global Forum, we unpack each of these four issues and propose practical steps for successful and fruitful implementation. Our goal is to provide help in working our way through the neutral zone together. You can also get involved in this work by joining the DIA DEI Community.