THE SCALE OF PROLONGED UNCERTAINTY: ESTIMATING U.S. PATIENT POPULATIONS AFFECTED BY OVERDUE ACCELERATED APPROVAL CONFIRMATORY TRIALS
Author(s)
Mouna Dardouri, MPH, PharmD, Michael J. DiStefano, PhD;
University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, CO, USA
University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, CO, USA
OBJECTIVES: To quantify the U.S. population potentially exposed to Accelerated Approval (AA) therapies with delayed confirmatory postmarketing requirements (PMRs) representing patients living with ongoing uncertainty as of January 2026.
METHODS: We used the FDA PMR searchable database to identify AA PMRs with original final report due dates before 12/31/2025 and a status of “Ongoing” or “Delayed.” For each overdue PMR, we abstracted the drug and its AA indication and paired each indication with the best available U.S. epidemiologic inputs from the literature. Eligibility criteria described in each indication (such as advanced or metastatic disease, specific tumor type or biomarker, and prior treatment requirements) were applied step by step to narrow the underlying disease population to patients who would meet the indication, using estimates from peer-reviewed sources. Infectious disease products were excluded from prevalence pooling because eligibility often reflects broad preventive populations rather than patients living with the treated condition.
RESULTS: We identified 24 delayed AA PMRs with due dates before 12/31/2025. 83% (20/24) were oncology indications. 29% (7/24) were more than 12 months past the original due date as of 1/1/2026; the median time past due was ~4.6 months (ranging from 1 day to 59 months). After excluding infectious disease products, the smallest estimated eligible prevalent population was for afamitresgene autoleucel in unresectable or metastatic synovial sarcoma (~334 patients). The largest estimated eligible prevalent population was for adagrasib in KRAS G12C-mutated metastatic non-small cell lung cancer (~33,700-36,500 patients).
CONCLUSIONS: As of January 2026, overdue AA confirmatory requirements remain common and include both rare disease and indications affecting tens of thousands of patients. When confirmatory trials are delayed, questions about the balance of benefit and harm and the value of therapies remain unresolved. This uncertainty affects treatment decisions, resource allocation, and coverage determinations, reinforcing the need for timely completion and clear monitoring of confirmatory studies.
METHODS: We used the FDA PMR searchable database to identify AA PMRs with original final report due dates before 12/31/2025 and a status of “Ongoing” or “Delayed.” For each overdue PMR, we abstracted the drug and its AA indication and paired each indication with the best available U.S. epidemiologic inputs from the literature. Eligibility criteria described in each indication (such as advanced or metastatic disease, specific tumor type or biomarker, and prior treatment requirements) were applied step by step to narrow the underlying disease population to patients who would meet the indication, using estimates from peer-reviewed sources. Infectious disease products were excluded from prevalence pooling because eligibility often reflects broad preventive populations rather than patients living with the treated condition.
RESULTS: We identified 24 delayed AA PMRs with due dates before 12/31/2025. 83% (20/24) were oncology indications. 29% (7/24) were more than 12 months past the original due date as of 1/1/2026; the median time past due was ~4.6 months (ranging from 1 day to 59 months). After excluding infectious disease products, the smallest estimated eligible prevalent population was for afamitresgene autoleucel in unresectable or metastatic synovial sarcoma (~334 patients). The largest estimated eligible prevalent population was for adagrasib in KRAS G12C-mutated metastatic non-small cell lung cancer (~33,700-36,500 patients).
CONCLUSIONS: As of January 2026, overdue AA confirmatory requirements remain common and include both rare disease and indications affecting tens of thousands of patients. When confirmatory trials are delayed, questions about the balance of benefit and harm and the value of therapies remain unresolved. This uncertainty affects treatment decisions, resource allocation, and coverage determinations, reinforcing the need for timely completion and clear monitoring of confirmatory studies.
Conference/Value in Health Info
2026-05, ISPOR 2026, Philadelphia, PA, USA
Value in Health, Volume 29, Issue S6
Code
HPR156
Topic
Health Policy & Regulatory
Disease
No Additional Disease & Conditions/Specialized Treatment Areas