Adaptive designs in clinical trials

Abstract

In addition to the expensive and lengthy process of developing a new medicine, the attrition rate in clinical research was on the rise, resulting in stagnation in the development of new compounds. As a consequence to this, the US Food and Drug Administration released a critical path initiative document in 2004, highlighting the need for developing innovative trial designs. One of the innovations suggested the use of adaptive designs for clinical trials. Thus, post critical path initiative, there is a growing interest in using adaptive designs for the development of pharmaceutical products. Adaptive designs are expected to have great potential to reduce the number of patients and duration of trial and to have relatively less exposure to new drug. Adaptive designs are not new in the sense that the task of interim analysis (IA)/review of the accumulated data used in adaptive designs existed in the past too. However, such reviews/analyses of accumulated data were not necessarily planned at the stage of planning clinical trial and the methods used were not necessarily compliant with clinical trial process. The Bayesian approach commonly used in adaptive designs was developed by Thomas Bayes in the 18th century, about hundred years prior to the development of modern statistical methods by the father of modern statistics, Sir Ronald A. Fisher, but the complexity involved in Bayesian approach prevented its use in real life practice. The advances in the field of computer and information technology over the last three to four decades has changed the scenario and the Bayesian techniques are being used in adaptive designs in addition to other sequential methods used in IA. This paper attempts to describe the various adaptive designs in clinical trial and views of stakeholders about feasibility of using them, without going into mathematical complexities.

Keywords: Adaptive designs; Bayesian approach; interim analysis; randomization; sequential methods.