Adaptive Clinical Trial Design

Published December 2016 Updated September 2017 12 lectures
Prof. Yu Shyr
Vanderbilt University Medical Center, USA
Summary

The biopharmaceutical industry spends about $100 billion per year worldwide on clinical drug development; yet, nearly half of the studies have failed in Phase 3 trials or have trials with an incorrect dose. Therefore, a more efficient trial design with fewer patients, a shorter study duration, a better likelihood of... read moredemonstrating the true drug effect, and a quicker, more informative decision on continuing or discontinuing the trial, is essential for improving trial failure or incorrect dose selection rate. A trial design with adaptive features, such as changes in design or analysis based on the accumulated data during the trial progress, has the potential to improve the efficiency of the trial design. Interest in these designs has grown substantially.
The statistical methodology publications on adaptive trial design approaches have grown significantly since the 1990s. The implementation of newly developed approaches in drug development has raised interest among regulators, academia, and industry. Both the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have published guidance documents addressing the potentials as well as the limitations of adaptive clinical designs in the regulatory context.
This course examines the adaptive clinical trials design and analysis, and focuses on the theoretical and practical issues related to the frequentist and the Bayesian-based framework.
The first section of the course provides a foundation on adaptive trial design, including an overview of the design, regulatory guidance, basic Bayesian inference, and a step-by-step procedure in Bayesian trial design.
The second section of the course focuses on the implementation of adaptive clinical trials, such as adaptive randomization, Phase I, Phase II, Phase II/III seamless, Phase III, and biomarker adaptive design for targeted therapy trials. A number of cases in superior, non-inferior, and equivalent trials will be discussed.
The third section of this course includes sample size estimation, interim analysis, and issues related to statistical data analysis.
The last section of the course focuses on special issues such as ethical and practical challenges that range from a single-country trial to a multi-country adaptive trial.
Each lecture will be presented by a renowned expert in the field, providing an account of principles, current knowledge and methods, and a future direction in the adaptive clinical trials field. We hope the lectures in this course will build a solid foundation for an audience who is interested in learning about adaptive clinical trials and in ultimately improving the success rate of new drug development.