Expedited pathway portfolios, trial complexity, and FDA approval timelines in oncology and neurology: A comparative analysis

Vollständiger Abstract

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FDA expedited programs are intended to facilitate development and review for therapies addressing serious conditions with unmet medical need, but their use may depend on whether the evidentiary package is compatible with regulatory acceleration. We compared FDA original approvals in oncology and neurology from 2015 to 2024 to evaluate whether differences in approval timing reflected expedited pathway portfolio intensity, pivotal evidence architecture, or alignment between the two. We conducted a retrospective comparative cohort study of 195 original FDA approvals, including 136 oncology products and 59 neurology products. Product-level regulatory data were curated from FDA approval materials. Pivotal or registrational trials supporting first approval were identified from FDA labels and review documents and enriched through exact National Clinical Trial identifier matching to AACT. The final evidence dataset included 221 curated product–trial links. Regulatory pathway-portfolio intensity was summarized using a Regulatory Bundling Index incorporating Fast Track, Breakthrough Therapy designation, Priority Review, Accelerated Approval, and Orphan designation. Outcomes included regulatory approval time, clinical development time, total time to approval, and pivotal evidence architecture. Oncology products had higher pathway intensity than neurology products, with median Regulatory Bundling Index 3 [IQR, 2–4] versus 2 [IQR, 0–3] (p < 0.001). Neurology products had longer regulatory approval time than oncology products: 362 days [IQR, 245–366] versus 234 days [IQR, 182–329] (p < 0.001). In contrast, clinical development time and total time to approval did not differ significantly. Neurology pivotal evidence was more often randomized, masked, and late phase, while oncology evidence was more often single group. Trial enrollment did not differ significantly. In exploratory counterfactual analyses, increasing neurology pathway intensity to the oncology median was associated with a median predicted review-time reduction of 37.8 days. Differences in FDA approval timing between oncology and neurology appear to reflect both pathway configuration and pivotal evidence architecture. These findings support a pathway-evidence alignment framework rather than a simple model in which more expedited designations alone explain faster approval.