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P04: A Retrospective Regulatory Review: Leveraging Safety to Inform and Encourage Diverse and Inclusive Clinical Trial Enrollment

Poster Presenter

Timothy Kline

Manager, Global Regulatory Affairs
Janssen Pharmaceutical Companies of Johnson & Johnson
United States

Objectives

To drive awareness and encourage sponsors to increase enrollment of representative and diverse participant groups in clinical trials using an emerging data-driven retrospective analysis of post-marketing requirements issued for insufficient representative enrollment due to safety .

Method

This retrospective analysis began in 2019 with a manual correlation of multiple FDA databases (Post-Marketing Commitments [PMC/PMR] and Summary Basis of Approval) to query for PMC/PMR that likely originated from insufficient diverse representation due to safety and correlates to FDA review comments.

Results

Approximately 100 fields (5 fields from Drug Trial Snapshots, 24 fields from PMC/PMR database, and 50 fields from Summary Basis of Approval database) were accessed from the full databases and collated manually (spreadsheet comparisons), semi-automatically (relational database programs), and automatically (machine-learning algorithms). These 100 fields were analyzed for trends and relationships that may have triggered a PMC/PMR on account of clinical trial underrepresentation. A collection of safety-driven PMRs across multiple-diseases (cardiovascular, immunology, and oncology) on account of underrepresentation of key demographics was found. Most case studies in the collection were found to correlate to specific review comments from the FDA Division responsible for approval of the product. Both manual and semi-automated methods of analysis identified the same case studies. The current dataset size appears to be insufficient in size for machine-learning. The evolving hypothesis is that the rate of issued PMRs may only increase or exacerbate to other more detrimental circumstances for both the sponsor and public if current trajectories are unchanged.

Conclusion

Yet, a brief review of recent Drug Trial Snapshots show that patients who currently participate in clinical trials for new drugs continue to skew heavily white – in some cases, 80 to 90 percent. FDA Drug Trials Snapshots (N = 46,000 patients, 48 new drugs/treatments, 2019) show that demographic breakdown was: White/Caucasian – 72%; Hispanic/LatinX – 18%; Black/African American – 9%; and Asian – 9%. Clinical trial participants for cancer, a significant health concern within communities of color (in 2019) represented less than 10% of the total study population. There are several reasons for underrepresentation by minority groups in the U.S., including: 1) a lack of accurate information and understanding about clinical research; 2) mistrust in medical care and clinical research that can be traced back to historical events; and 3) unfamiliarity on where to access information about clinical trial opportunities. However, ethnic and racial demographics in the U.S. will continue to rapidly shift and will approach a threshold without a single racial or ethnic majority by about 2055. Now is the time to act to commit to diverse and inclusive trials built on a solid foundation of data (inclusive of retrospective analyses) and candid conversations/outreach to the communities most in need.