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An adaptive dose-finding design incorporating both toxicity and efficacy

Wei Zhang1, Daniel J Sargent, Sumithra Mandrekar

  • 1Department of Biostatistics, University of Iowa, Iowa City, IA 52242, USA.

Statistics in Medicine
|October 13, 2005
PubMed

Insights

This study introduces TriCRM, a novel approach for phase I clinical trials. TriCRM optimizes drug dose selection by integrating both toxicity and efficacy data, improving novel therapy development.

Area of Science:

  • Clinical Pharmacology
  • Biostatistics
  • Drug Development

Background:

  • Novel therapies require innovative drug development strategies.
  • Determining optimal doses for targeted agents with low toxicity is challenging.
  • Phase I trials need efficient designs to advance promising treatments.

Purpose of the Study:

  • To present a novel dose-finding approach for phase I trials.
  • To integrate both toxicity and efficacy data for optimal dose estimation.
  • To introduce the TriCRM design for biologically optimal dose selection.

Main Methods:

  • Utilizes a flexible continuation-ratio model.
  • Employs straightforward optimal dose selection criteria.
  • Incorporates a continual reassessment method (CRM) for adaptive dose adjustments.

Main Results:

  • The TriCRM design effectively estimates the biologically optimal dose.
  • Considers various dose-outcome relationships (increasing, decreasing, unimodal).
  • Simulation studies confirm favorable operating characteristics of TriCRM.

Conclusions:

  • TriCRM offers an improved method for dose selection in early-phase drug development.
  • This approach enhances the efficiency of identifying optimal doses for novel agents.
  • The integration of toxicity and efficacy data leads to more robust dose determination.

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