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Identifying a maximum tolerated contour in two-dimensional dose finding.

Nolan A Wages1

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

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Summary
This summary is machine-generated.

This study introduces a new dose-finding method for multi-agent trials, extending the continual reassessment method to identify multiple maximum tolerated dose combinations (MTDCs) for improved phase II efficacy testing.

Keywords:
dose findingdrug combinationequivalence contourphase I

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Area of Science:

  • Biostatistics
  • Clinical Trials
  • Pharmacology

Background:

  • Traditional phase I clinical trials often aim to find a single maximum tolerated dose combination (MTDC).
  • Alternative approaches consider that multiple dose combinations may represent an acceptable toxicity contour.
  • Identifying multiple MTDCs could enhance subsequent phase II efficacy studies.

Purpose of the Study:

  • To present a novel dose-finding methodology for multi-agent trials.
  • To extend the continual reassessment method (CRM) for identifying multiple MTDCs.
  • To facilitate the selection of optimal dose combinations for phase II trials.

Main Methods:

  • Development of an extended continual reassessment method (CRM).
  • The proposed method accounts for the potential existence of multiple MTDCs.
  • Simulation studies are employed to evaluate operating characteristics.

Main Results:

  • The new method demonstrates its utility in identifying multiple MTDCs.
  • Performance is compared against existing dose-finding methodologies.
  • Simulation results highlight the method's operating characteristics.

Conclusions:

  • The presented method offers a valuable extension to existing phase I trial designs.
  • It enables the identification of multiple MTDCs, potentially improving phase II trial efficiency.
  • Discussion on implementation and software availability is provided.