Lessons Learned from a Delayed Start Trial Review Experience

• Activity Number: 223
• Type: Topic Contributed
• Date/Time: Monday, July 30, 2012 : 2:00 PM to 3:50 PM
• Sponsor: Biopharmaceutical Section
• Author(s): Tristan Massie*+
• Companies: FDA

Abstract

Some experts question whether a single phase design using a subjective endpoint can establish disease modification without complementary data such as possibly effects on biomarkers. This, in part, led to the delayed start design. I will discuss lessons learned from the experience of reviewing a delayed start design trial. Some pre-existing concerns about the delayed start design were validated by the trial results. For example, the trial's prespecified margin would have allowed a conclusion of noninferiority of slopes, in one case, despite the fitted lines actually crossing. In the given trial the subjects remaining for the analysis of the second phase showed imbalances between treatment groups in some crucial baseline covariates, suggesting that the randomization was broken. This highlights the fact that prevention of Missing Data is critical for interpretation of the second phase of such trials. On the other hand there were considerable dropouts due to the length of trial period and the nature of the degenerative disease. Other issues and insights from an FDA advisory committee will be discussed too. This presentation should not be construed to represent FDA's views or policies.