Adapting to Adaptive Studies

Adaptive clinical research promises profound and dramatic benefits to the pharmaceutical industry. Adaptive programmes, which allow changes during a trial based on analysis of data collected up to the time of the change, provide major advances such as shortening development time, reducing the incidence of treating patients with ineffective or unsafe doses, and allowing regulatory agencies a more nuanced assessment of both efficacy and safety.

Several trends have converged to enable adaptive methods, including increased computational power, more efficient communications technology, and powerful supporting statistical methodologies. Agencies such as the US Food and Drug Administration and the EMEA have acknowledged the significance of adaptive methods in a variety of ways. Moreover, the direct experience of research groups that deal regularly with relevant design and reporting issues, including my own, confirms not only a growing receptiveness of regulators to adaptive methods, but also encouragement of well designed adaptive studies.

This article summarises the organisational and process issues in adaptive research. After briefly discussing the principles of adaptive research and the types of optimisations an adaptive trial can enable, the focus for the balance of the article will shift to what is required to make the powerful engine of adaptive research deliver maximum benefits.

WHAT IS ADAPTIVE RESEARCH?

The term ‘adaptive research’ broadly denotes changes that can occur during the course of a study or development programme without compromising validity or integrity. An adaptive trial design can correct mistaken assumptions or seize an opportunity to optimise the trial. Often the result is shorter timelines, lower costs and superior information for sponsors, regulators and future prescribing physicians.