Redefining the Gold Standard

February 2019
Authors: Chitra Lele and Ritu Budania, Sciformix – A Covance Company

Adaptive clinical trials have risen in popularity and gained more attention since the FDA Critical Path Initiative (2004) and Critical Path Opportunity List (2006) called for innovative solutions to transform the way medicinal products are developed, evaluated, and manufactured. They are now being commonly used to quickly predict the likelihood of the success or failure of a drug in early stages of drug development.

The release of the FDA’s draft guidance in 2010 on “adaptive design clinical trials for drugs and biologics” provided a
suggested framework for designing such studies and for using them to make decisions that would allow the innovator to “fail early.” EMA’s Committee for Medicinal Products for Human Use released a similar draft in 2006 (1).

Adaptive designs have been widely used over the past decade, largely focussed on early development, especially
Phase 2 studies, although they have also been used in confirmatory clinical trials. Adaptive clinical trials provide
more flexibility and look to improve the efficiency and speed of clinical trials.

Due to the complexity of adaptive designs, the FDA encourages more extensive interactions between the
sponsor and the FDA, therefore, sponsors may seek feedback from the FDA. However, the EMA reflection paper on adaptive trials has advised a more cautionary approach, suggesting use in late Phase 2 (1). The EMA acknowledged the problems increased flexibility can cause. Furthermore, a joint workshop organised by US and EU regulators, academia, and industry experts advised the use of adaptive designs in exploratory studies only. The workshop did not recommend use in confirmatory studies (2).

Certain types of adaptive designs are used more commonly, eg, adaptation for sample size re-estimation, testing for
futility, etc. However, many other types of adaptive designs exist, which may not be as well-known. This article will
provide a summary of the most common adaptations used, along with their different objectives, benefits, and challenges.

Read the full article.