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Implementation of adaptive methods in early-phase clinical trials

Gina R Petroni1, Nolan A Wages1, Gautier Paux2

  • 1Division of Translational Research and Applied Statistics, Department of Public Health Sciences, The University of Virginia, Charlottesville, VA, 22908, U.S.A.

Statistics in Medicine
|March 2, 2016
PubMed

Insights

Despite advances in statistical methods for early-phase clinical trials, the traditional 3+3 design is still common. This article guides protocol development to encourage adoption of advanced, model-based dose-finding designs.

Area of Science:

  • Biostatistics
  • Clinical Trial Design
  • Pharmacology

Background:

  • The traditional 3+3 design is widely used in early-phase clinical trials for dose-finding, despite known limitations compared to innovative statistical methods.
  • Model-based designs offer more efficient dose-finding but are infrequently adopted due to poor understanding and evaluation challenges.
  • Drug development trends towards complex dose-finding problems, necessitating more advanced statistical approaches.

Purpose of the Study:

  • To review essential information for clinical trial protocols to facilitate acceptance and approval of novel statistical designs.
  • To provide practical guidance for implementing efficient, model-based dose-finding designs.
  • To support the transition from traditional algorithmic designs to adaptive model-guided designs in early-phase trials.

Main Methods:

  • Literature review of statistical methods in early-phase clinical trial design.
  • Analysis of barriers to adoption of model-based designs.
  • Guidance development for protocol content and trial implementation.

Main Results:

  • Identification of key information required in protocols for novel design approval.
  • Practical strategies for implementing efficient adaptive designs.
  • Considerations for the practical execution of approved novel trial designs.

Conclusions:

  • Enhanced protocol content and practical guidance can overcome barriers to adopting advanced statistical designs.
  • Facilitating the transition to model-guided adaptive designs is crucial for modern drug development.
  • Addressing implementation challenges is key to realizing the benefits of innovative dose-finding methodologies.
Keywords:
adaptive methodsdose-findingprotocol development

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