General considerations about adaptive trials


Tutorial papers

There are some easy-to-read papers discussing the concept of adaptive designs and real-life case studies as well as general practical considerations:

  • Burnett et al.   Adding flexibility to clinical trial designs: an example-based guide to the practical use of adaptive designs. BMC Med. 2020;18(1):352. 
  • Pallmann et al. Adaptive designs in clinical trials: why use them, and how to run and report them. BMC Med. 2018;16:29.
  • Park et al. Critical concepts in adaptive clinical trials. Clin Epidemiol. 2018;10:343–51. 
  • Thorlund et al. Key design considerations for adaptive clinical trials: A primer for clinicians. BMJ. 2018;p. k698 
  • Stallard et al. Efficient adaptive designs for clinical trials of interventions for COVID-19. Stat Biopharm Res. 2020;1–26. 
  • Porcher et al. Adaptive methods: when and how should they be used in clinical trials? Therapie. 2011;66:319–26.

Easy-to-read books with case studies

These are some of non-technical and practical oriented books suitable for multidisciplinary audience. They also cover useful real-life case studies and considerations when using adaptive designs:

  • Rosenberg. The agile approach to adaptive research: optimizing efficiency in clinical development. John Wiley & Sons, Inc. 2010 
  • He et al. Practical considerations for adaptive trial design and implementation. Springer. 2014

Statistical books

These are some of the available books for statisticians who may want to know about about statistical issues around adaptive methods:

  • Proschan et al. Statistical monitoring of clinical trials - A unified approach. Springer. 2006
  • Wassmer and Brannath. Group sequential and confirmatory adaptive design in clinical trials. Springer. 2016
  • Whitehead. The design and analysis of sequential clinical trials. John Wiley & Sons Ltd. 2000

Guidance on costing of adaptive trials

1. Wason et al. Practical guidance for planning resources required to support publicly-funded adaptive clinical trials. BMC Med. 2022

Protocol guidance

Although the following guidance paper was developed in the context of early phase trials, the guiding principles are similar so it can be easily adapted and used to inform the development of protocols in late phase trials.

  • Lorch et al. Three steps to writing adaptive study protocols in the early phase clinical development of new medicines. BMC Med Res Methodol. 2014;14:1–9. 

Reporting guidance

Researchers are encouraged to use the official CONSORT extension for randomised adaptive trials. This Adaptive designs CONSORT Extension (ACE) is publicly accessible via several platforms:

Regulatory guidance

FDA. Adaptive designs for clinical trials of drugs and biologics. Guidance for Industry. 2019. 

Statistical guidance on simulations

Mayer et al. Simulation practices for adaptive trial designs in drug and device development. Stat Biopharm Res. 2019;11(4):325–35.

Online resources

Open access statistical resources


MEDIANA Adaptive Designs Toolkit

The R package (MedianaDesigner) supports simulation-based power and sample size calculations for a broad class of late-stage clinical trials, including adaptive dose-finding phase II and confirmatory phase III trials. The following adaptive designs are currently supported: 

  • phase II trials with response-adaptive randomisation, 
  • phase III trials with data-driven sample size or event count re-estimation, 
  • phase III trials with data-driven treatment selection, 
  • phase III trials with data-driven population selection. 
The package enables efficient clinical trial simulations for most commonly used types of trial designs; e.g., phase III designs with one or two interim analyses, and emphasizes user-friendly features such as the availability of a graphical user interface (shiny-based applications) and comprehensive simulation reports (Microsoft Word documents).
 For more information about the package, as well as the online manual with case studies and technical documentation. A ten-part online training course with a general introduction to adaptive designs, a review of relevant statistical and regulatory considerations, case studies, and instructional videos for the software is available at Mediana’s YouTube channel.