One way to understand FDA’s health priorities is to listen to FDA Commissioner, Robert Califf. In the 8 February 2024 article published in New England Journal of Medicine, Califf touched on the need to address chronic diseases in the United States (US) and how FDA is approaching this problem by targeting innovations in clinical research and regulatory policy.

UNMET NEED

• Seven of the 10 most common causes of death in the US are chronic diseases including heart disease, cancer, Alzheimer’s disease, diabetes, and chronic lung, liver, and kidney diseases.
• 58% of adults have two or more chronic diseases and one in five people in their 20s have multiple chronic diseases.
• Chronic diseases disproportionally impact low-income, rural, tribal, and marginalized populations.

FDA’s APPROACH

The legal and regulatory tools that FDA has support development of safe and effective interventions for the treatment and prevention of diseases. Califf’s NEJM article summarizes how FDA is approaching the chronic diseases challenge in the US, which in turn provides sponsors a window into FDA’s thinking on what clinical trial approaches would pass muster with the FDA.

• Since chronic diseases require larger and long-duration trials which could be costly, FDA supports use of biomarkers and surrogate endpoints for efficacy.
• FDA supports research on the development and evaluation of reliable biomarkers and surrogate endpoints for outcomes of interest. FDA and the National Institutes of Health have jointly developed the Biomarkers, Endpoints, and Other Tools (BEST) Resource and standardized terminology.
• Since chronic diseases impact a large segment of population, FDA prefers generalizable trials with less restrictive eligibility criteria.
• FDA supports pragmatic trials (including those incorporating decentralized elements) to address enrollment of wide cross-section of population that is representative of the disease impact. Larger, simpler, practical trials with decentralized designs could be cheaper and also suitable for generating reliable premarketing and postmarketing evidence on diagnostics and therapeutics for common chronic diseases.
• FDA supports the use of technology such as electronic health records as a surrogate for long-term safety monitoring during postmarketing surveillance.
• FDA has interest in fostering patient engagement and patient-focused drug development including use of patient-reported outcomes in clinical trials. Diagnostic tests, including at-home tests, are also on FDA’s radar since they improve patient engagement with their own health.
• FDA cautions that diversity and access objectives should not be overlooked: “Both diagnostic and therapeutic interventions must be broadly accessible across groups based on age, sex, gender, race, ethnicity, coexisting conditions, income, food and housing security, geography, education, and degree of health and digital literacy.”
• FDA has become strict in requiring and enforcing trial diversity plans and has also issued industry guidance with a goal of increasing trial enrollment among older adults with multiple coexisting conditions.
• FDA is also using its authority to obtain postapproval evidence and require confirmatory trials for interventions, where applicable.

SOURCE

• Warraich HJ, Marston HD, Califf RM. Addressing the Challenge of Common Chronic Diseases - A View from the FDA. N Engl J Med. 2024 Feb 8;390(6):490-492. doi: 10.1056/NEJMp2313217. PMID: 38314843.
• FDA-NIH Biomarker Working Group. BEST (Biomarkers, Endpoints, and other Tools) Resource [Internet]. Silver Spring (MD): Food and Drug Administration (US); 2016-. NCBI Books.
• Read about FDA Commissioner, Robert Califf at Wikipedia, STAT News Profile [archive]

Related posts: diversity plans, FDA's Project Pragmatica, FDA guidance on decentralized trials, patient involvement in trial design