Year: 2026
Type: article
Abstract: The recent decision to establish a single pivotal trial as the default evidentiary standard for Food and Drug Administration (FDA) approval marks a substantive shift in the architecture of regulatory proof. This marks a shift from replication-based validation to a coherence-based model of sufficiency, beyond a procedural adjustment. Because FDA standards likely influence global development strategies, this change will likely extend beyond the United States. Although accelerating access and reducing development costs are legitimate objectives, the reform raises methodological and epistemological concerns. The statistical rationale does not fully incorporate the contextual factors that influence false-positive risk, including prior plausibility and statistical power. Prior plausibility remains informal, and post-marketing evidence seldom restores the epistemic security provided by independent replication. Replication is not merely a statistical redundancy but rather a structural safeguard of robustness and external validity. Without explicit safeguards, increased regulatory flexibility may generate heterogeneity in evidentiary thresholds and progressively weaken the discriminative function of health technology assessment.
DOI: 10.1111/fcp.70110
Institutions: Lyon 1 Université, Centre National de la Recherche Scientifique, Hospices Civils de Lyon, Laboratoire de Biométrie et Biologie Evolutive, Institut universitaire de cardiologie et de pneumologie de Québec, Université Laval, Inserm, Université Paris-Saclay, Centre de recherche en Epidémiologie et Santé des Populations, Institut de Recherche en Santé, Environnement et Travail, CIC Rennes, Centre Hospitalier Universitaire de Rennes, Université de Rennes, Centre Hospitalier Universitaire de Grenoble, Université Paris Cité
Language: English
Subfield: Statistics and Probability
Field: Mathematics
Domain: Physical Sciences
Open Access status: hybrid
Estimated APC paid: $3,300
OpenAlex ID: W7202382149