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Related Experiment Videos

Two-sample continual reassessment method.

J O'Quigley1, L Z Shen, A Gamst

  • 1Department of Mathematics, University of California, San Diego, La Jolla 92093, USA.

Journal of Biopharmaceutical Statistics
|March 26, 1999
PubMed
Summary
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This study extends the continual reassessment method (CRM) for phase I trials to accommodate two patient groups. The two-sample CRM offers optimal dose-finding when groups differ but share characteristics, improving patient safety.

Area of Science:

  • Biostatistics
  • Clinical Trial Design
  • Pharmacology

Background:

  • Phase I clinical trials aim to find the maximum tolerated dose (MTD).
  • Traditional methods often treat patient populations as homogenous.
  • Adapting dose-finding methods for heterogeneous patient groups is crucial for safety and efficacy.

Purpose of the Study:

  • To extend the continual reassessment method (CRM) for phase I dose-finding studies involving two distinct patient groups.
  • To evaluate a novel two-sample CRM that models relationships between dose-toxicity curves of two groups.
  • To compare the performance of the two-sample CRM against single-sample CRM applied separately or to pooled data.

Main Methods:

  • Developed a bivariate CRM incorporating a specified relationship between dose-toxicity curves for two patient groups.

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  • Employed maximum likelihood estimation for the bivariate model.
  • Conducted extensive simulations under various model misspecifications to assess performance.
  • Provided asymptotic results to support simulation findings.

    • Main Results:

    • The two-sample CRM performs best when patient groups are different but share some characteristics.
    • When groups are highly dissimilar, separate single-sample CRMs offer comparable finite-sample performance with better asymptotic efficiency.
    • Pooling data (ignoring heterogeneity) is optimal only when groups are truly homogeneous.
    • The two-sample approach is particularly beneficial when subgroup sizes are small.

    Conclusions:

    • The proposed two-sample CRM effectively adapts dose-finding for two-group studies.
    • The method provides a flexible and robust approach to MTD determination in heterogeneous populations.
    • Choosing the appropriate method (two-sample, separate single-sample, or pooled) depends on the degree of patient heterogeneity.