Standards Needed for Defining Rare Disease Populations: Congress

U.S. representative Josh Gottheimer (D-NJ) and thirty-eight of his colleagues sent a bipartisan letter to HHS and FDA urging them to establish clear, consistent standards for defining rare disease patient populations. The lawmaker is the founder and co-chair of the Congressional Sarcoidosis Caucus.

“When 95% of rare diseases do not have cures, we cannot risk discouraging innovation in areas where scientific progress is rapidly outpacing regulatory adaptation,” the letter says. “These challenges are not merely technical — they have real implications for patients… This means if the FDA considers prevalence rate with the higher estimate as the prevailing rate, diseases like Sarcoidosis are no longer capable of receiving crucial rare disease funding to find cures even though the patient population that needs treatment is well below the current FDA standard for rare.”

The letter takes issue with the lack of clear, consistent FDA standards on how patient populations should be defined, how prevalence should be measured, and what evidentiary standards sponsors must meet. “Advances in genomics and precision medicine are enabling researchers to identify increasingly specific disease subtypes, but the FDA has no clear roadmap for how to characterize those populations in regulatory submissions,” Gottheimer say in a release, adding that the uncertainty can discourage investment in therapies for small or complex patient populations.

The lawmaker says diseases like sarcoidosis risk losing rare disease status depending on how patient populations are counted. “For example, while some estimates place sarcoidosis prevalence just above 200,000, only about 60,000 patients actually require treatment,” he says. “If the FDA relies on the higher estimate, diseases like sarcoidosis could lose access to rare disease-specific research funding and incentives, even though the population that needs treatments is well below the 200,000-person threshold.”

The lawmakers urge HHS and FDA to:

• Establish standardized definitions of how patient populations are delineated, including the role of genetic, biomarker, and clinical criteria.
• Issue clear guidance on acceptable methodologies for calculating and submitting prevalence data, including preferred data sources, timeframes, and analytic approaches.
• Outline how real-world data and registry-based studies should be incorporated into regulatory submissions.
• Provide greater transparency into how population definitions and prevalence estimates are evaluated during review.
• Clarify the role of treatment-eligible patient populations in determining rare disease status.
• Engage patient groups, researchers, and industry to develop consensus-driven best practices for population identification and data submission.