Report of a Workshop on Confirmatory Evidence to Support a Single Clinical Trial as a Basis for New Drug Approval *

Abstract

A novel approach for more efficient, economical, and faster clinical evaluation of new drugs is to couple effectiveness data from phase 2 and other studies with a phase 3 single clinical trial (SCT) for regulatory approval. Sanctioned in the Food and Drug Administration Modernization Act (FDAMA), this approach challenges the traditional requirement for two controlled phase 3 trials for approving a new therapy. Academic, industry, legal, and regulatory experts participated in a workshop to define adequate confirmatory evidence of effectiveness to support regulatory approval based on data from an SCT Participants examined qualities of confirmatory evidence and SCTs and implications of this model for clinical safety information. Acknowledging the evolutionary nature of scientific evidence of effectiveness, participants identified risks and benefits of this approach, concerns of FDA and pharmaceutical companies, and policy changes that may further encourage widespread use of the confirmatory evidence-SCT model. For example, these policy changes include explicit FDA publication of the basis for effectiveness determinations of new drugs, use of end-of-phase 1 industry-regulator meetings for prospective planning of the confirmatory evidence-SCT program, and more use of established pharmacological knowledge to qualify confirmatory evidence biomarkers and surrogate endpoints.