Evaluating Effectiveness of a New Treatment Indication: A Succession of Clinical Trials with Varying Estimands

• Activity Number: 290
• Type: Invited
• Date/Time: Tuesday, August 11, 2015 : 8:30 AM to 10:20 AM
• Sponsor: Biopharmaceutical Section
• Author(s): Scott Emerson*
• Companies: University of Washington
• Keywords: missing data ; RCT

Abstract

An "indication" for a new therapy is a unique combination of a disease, a patient population, a treatment strategy, and a desired clinical outcome. Prior to adoption of such a therapy, we would like to have high confidence of its safety, efficacy, and effectiveness. The various phases of randomized clinical trials are the mainstays of this process-- a process that has always been sequential and adaptive. A major challenge of that process is how to best focus on the eventual use of the therapy in clinical practice, all the while ensuring the scientific and statistical rigor inherent in a randomized intervention. In this talk I discuss some RCT design strategies that might be used to allow rigorous, per randomization analyses to identify treatments that are safe and effective when the patients enrolled in the RCT might ultimately have very different exposures to the study drug. I focus on the role that "intent-to-treat" and "per protocol" estimands might be evaluated in successive randomized trials in order to best address the public health and regulatory needs.