February 1, 2024 Webinar
Reflections on Clinical Trial Futility Decisions and Approval Strength of Evidence from the Aducanumab Saga
Paul Gallo, PhD
Abstract:
Two issues arising in clinical development where statistical methods play a fundamental role, and which one might perhaps expect never to arise within the same clinical program, are: stopping ongoing trials for so-called "futility" when interim results are very weak; and quantifying the degree of favorable evidence necessary for regulatory approval of an investigational therapy. However both of these issues did indeed arise in a clinical development program for aducanumab, a potential breakthrough therapy to slow decline in Alzheimer's disease patients. Two pivotal trials of aducanumab were underway when it was announced that the program would be terminated for futility based on poor results seen at an interim analysis; eventually these same trials became the basis for regulatory submissions, which led to an FDA Advisory Committee hearing that had some unusual intriguing aspects, and ultimately to a somewhat controversial regulatory decision. We use this case as a motivating example to discuss challenges in implementing futility plans and making futility decisions; we also touch upon issues involving how overall strength of evidence from a clinical program might be interpreted.
Short Bio:
Paul Gallo received a Ph.D. from the Department of Statistics at UNC-Chapel Hill in 1982. He recently retired after a 40-year career in the pharmaceutical industry, the last 30 of which were at Novartis Pharmaceuticals in East Hanover NJ, where he served as Senior Biometrical Fellow and Executive Director of Biostatistics. He was a member of Novartis's Statistical Methodology Group since its inception in 2000. In that role, he provided statistical training and methodological support to projects across all areas of the organization's clinical investigations. He played a prominent leadership role in influential industry working groups on adaptive clinical trial designs and multiregional clinical trials. He is an author of 76 publications in the scientific literature, and has given presentations or presented short courses at scientific conferences on over 100 occasions. He is a Fellow of the American Statistical Association, and served on ASA's Committee on Fellows, of which he was Chair in 2018.