Progress and Challenges in the FDA Accelerated Approval Pathway: A Policy Roadmap for HEOR

In this update, we analyze the evolution of the FDA Accelerated Approval Pathway since the 2022 Food and Drug Omnibus Reform Act (FDORA), highlighting measurable improvements, ongoing evidentiary gaps, and policy recommendations critical for health economics and outcomes research (HEOR), pricing, and reimbursement.

Reforms Driving Faster Evidence and Fewer Lingering Approvals

Recent legislative and regulatory updates have strengthened the FDA Accelerated Approval Pathway, particularly in oncology. Requirements that confirmatory trials be underway at approval, clearer surrogate endpoint expectations, a preference for randomized controlled trials when feasible, and expedited withdrawal authority have been well received by stakeholders. These changes have shortened the median time from accelerated approval to traditional approval in oncology from 4.3 years (1992–2013) to 2.3 years (2014–2024), while time to withdrawal has fallen from 9.5 to 3.2 years. Between 2021 and 2025, the FDA withdrew or facilitated the withdrawal of 25 oncology indications granted accelerated approval—compared with only six withdrawals from 1999 to 2021.

Therapeutic Area Differences Reveal Uneven Evidence Foundations

Significant challenges remain, and they vary sharply by disease area. In non-oncology rare diseases, ultra-rare conditions, and neurology, surrogate endpoints often rest on weak evidence, natural history data are limited, and small patient populations constrain trial design. High-profile cases such as elamipretide for Barth syndrome and delandistrogene moxeparvovec (Elevidys) for Duchenne muscular dystrophy have exposed regulatory ambiguities, mixed confirmatory results, and subsequent safety concerns that have damaged stakeholder trust. Even in oncology, where surrogates like progression-free survival are more established, one-third of products converted on the basis of progression-free survival between 2013 and 2017 later failed to show overall survival or quality-of-life benefits.

Pricing, Uncertainty, and Trust Issues Undermine Pathway Value

High launch prices that fail to reflect evidentiary uncertainty continue to drive restrictive coverage, prior authorization burdens, and patient financial toxicity. Asymmetric accumulation of safety versus efficacy data, delays in confirmatory trials, and limited public learning from negative results further erode payer confidence and slow scientific progress. These dynamics underscore the need for greater transparency in regulatory decision-making and more systematic approaches to surrogate endpoint validation.

HEOR Strategies and Value-Based Solutions for Sustainable Access

The persistent gap between surrogate and clinical outcomes calls for increased HEOR investment in surrogate validation, real-world evidence generation, and meta-analytic frameworks linking intermediate and final endpoints. Coverage restrictions for accelerated approval products are driven primarily by price and cost-effectiveness rather than the approval pathway itself. This reality supports earlier adoption of value-based pricing at launch, outcomes-based contracts targeted at areas of highest uncertainty, standardized contract templates, and centralized data collection. Waiving cost-sharing for drugs with no therapeutic alternatives could reduce financial toxicity without distorting incentives. Greater transparency—through standardized decision templates, public after-action reports on failed surrogates, and risk ratings—would improve shared decision-making and rebuild trust among manufacturers, payers, patients, and regulators.

Policy Roadmap to Strengthen Evidence and Align Incentives

Implementing systematic surrogate endpoint evaluation, scientific-focused drug development meetings, risk ratings, value-based pricing, targeted outcomes-based contracts, informed consent requirements, and tailored centers of excellence would reinforce the evidentiary foundation of the FDA Accelerated Approval Pathway. These steps would better align financial incentives with patient outcomes while preserving timely access to promising therapies for serious conditions.