Adaptive trial designs: opportunities and challenges
Vlad Dragalin, PhD
Janssen Pharmaceuticals Companies of Johnson & Johnson
The use of adaptive designs can increase the efficiency of drug development by improving our ability to efficiently learn about the dose–exposure--response and better determining whether to take a drug forward into latter phase testing and at what dose. Adaptive designs often employ frequent interim analyses of all accumulated data (and, possibly, external trial data) to determine whether pre-planned design modifications will be ‘triggered’. Interim analyses partition the trial into multiple stages, each trial stage’s characteristics (number of treatment arms, number of patients to be enrolled, their allocation between arms, stage duration, etc.) defined by the preceding interim analysis results. The ability to periodically, or even continually, examine available data to determine whether trial modifications are necessary and, when indicated, implement pre-defined design changes gives adaptive design its strength and flexibility.
We will provide an overview of available adaptive designs appropriate for drug development at different level: trial, program, and portfolio, including platform, umbrella, and basket designs. We will discuss also about the current trends seen across industry regarding uptake of adaptive designs. We will examine which types of adaptive designs are at the forefront, and those that are taking longer to gain traction, how the uptake of adaptive trial designs is not only a matter of design, but also a matter of finding solutions to sometimes complex trial execution challenges.
We will examine the pressure points within the execution process that are threats to trial integrity. The challenges of ensuring data remains blinded throughout the trial, that transcend beyond the usual focus point of managing the Data Monitoring Committee process itself, to the effect on monitoring and the project management practices. We will also go beyond the issues concerning confirmatory adaptive trials, to examine the additional execution challenges that affect exploratory stage adaptive trials.
For over a decade adaptive designs have been pushing at traditionally held beliefs and practices. Uptake may be slower than anticipated. However, through this session the audience will learn how progress is continuing to be made, and how the introduction of adaptive trials may ultimately lead to an overall improvement by industry in the way trial design options are evaluated and all trials are executed.