ABSTRACT
Dose . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 370 12.5 Multi-stage Designs, Group Sequential Designs, Interim
Analysis, Early Stopping for Toxicity, Efficacy, or Futility . . . . . 371 12.6 Sample Size Re-estimation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 372 12.7 Adaptive Randomization, Individual Ethics versus Group
Ethics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 373 12.8 Seamless Designs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 376 12.9 Biomarker-guided Adaptive Designs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 378 12.10 Multi-arm Adaptive Designs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 378 12.11 Master Protocols, Umbrella Trials, Basket Trials, and
Platform-based Designs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 385 12.12 Examples of Trials with Adaptive Designs — Lessons for Design
and Conduct . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 387 12.13 Software for Adaptive Designs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 390 12.14 Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 392
Glossary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 394 Acknowledgments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 395 Bibliography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 395
In this chapter, we focus on adaptive clinical trial designs that aim to improve the efficiency of research by more quickly answering the important questions
Trials: Issues in Design and
posed in the research protocol, identifying effective treatments and dropping ineffective treatments early, and providing the best treatments to the individual patients enrolled in clinical trials.
