Design of phase II ALS clinical trials

Abstract

Several important design issues for clinical trials in ALS were presented at the World Federation of Neurology conference at the International Motor Neuron Disease meeting in Yokahama, Japan. We present a discussion, and critique, of the important ideas that were presented with regard to phase II trials. In particular we critique the use of ‘Futility Designs’ because, as presented at the meeting they will too often lead to the testing of ineffective drugs. We show that except under a highly restrictive model, the use of a ‘Lead In’ period has only a minor effect on trial efficiency. We show the advantage of using multi‐drug phase II trials to select drugs for further study and the advantage of studies that combine phase II and III. We also describe how group sequential trials can be used to stop trials early.

• Clinical trials
• amyotrophic lateral sclerosis
• motor neuron disease
• futility
• lead in period
• group sequential trials
• endpoints
• survival