Regulatory Considerations in the Evaluation of Progression-Free Survival

• Activity Number: 339
• Type: Topic Contributed
• Date/Time: Tuesday, August 2, 2011 : 10:30 AM to 12:20 PM
• Sponsor: Biopharmaceutical Section
• Author(s): Rajeshwari Sridhara*+
• Companies: U.S. Food and Drug Administration
• Keywords: PFS ; Censoring rules

Abstract

Improvement in overall survival and patient reported outcomes provide direct clinical benefit to patients. However, consideration of progression-free survival (PFS) as the primary endpoint for demonstration of efficacy for approval of drug products is subject to demonstration of statistically persuasive effect & a magnitude of effect that will translate to a meaningful clinical benefit with an acceptable risk-benefit profile. In open label studies independent radiologic review is recommended as progression assessments are complex and subjective. This can result in informed censoring when the investigator and independent reviewers do not agree on the progression assessment. While we acknowledge that any choice of censoring rule in evaluating PFS has problems including informed censoring, the current FDA recommendation for the PFS analysis is that the PFS data be censored on the date of the last tumor assessment documenting absence of progression for patients who have no documented progression, or change therapy, or discontinue due to toxicity or personal preference. FDA's rationale for this current recommendation and ongoing research will be presented.