Challenges in Implementing Futility Schemes, with Reference to Aducanumab.

Stopping an ongoing clinical trial based on an interim analysis that shows poor outcomes, often referred to as a judgment of "futility", is a familiar feature in current clinical trials practice. Interim data can be misleading, and the implications of prematurely terminating a trial that should not stop are severe. It is thus critical that designs allowing futility stopping be planned and implemented carefully and cautiously. A recent Phase III development program for aducanumab in Alzheimer's disease was halted based on a pre-defined futility guideline, yet based upon updated data and closer examination, the terminated studies became the basis for a regulatory submission. Not surprisingly, this situation generated much controversy and discussion. It provides a good basis for illustrating important principles governing the planning and implementation of futility schemes.