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Updated: Aug 5, 2026

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An Escalation for Bivariate Binary Endpoints Controlling the Risk of Overtoxicity (EBE-CRO): Managing Efficacy and

P Colin1,2, M Delattre1,3, P Minini4

  • 1a AgroParisTech , UMR 518 MIA , Paris , France.

Journal of Biopharmaceutical Statistics
|April 5, 2017
PubMed

Insights

This study introduces a novel model-based design for early-phase oncology trials, balancing drug safety and efficacy. It aims to improve dose selection for molecular targeted agents, reducing costs and trial failures.

Area of Science:

  • Oncology
  • Clinical Trial Design
  • Biostatistics

Background:

  • Early-phase oncology trials face challenges with molecular targeted agents (MTAs).
  • Traditional maximum tolerated dose (MTD) is insufficient; early activity signals are crucial.
  • High costs and attrition rates necessitate efficient dose selection strategies.

Purpose of the Study:

  • To propose a model-based dose escalation design for early-phase oncology trials.
  • To integrate both safety (toxicity) and efficacy (activity) endpoints in trial design.
  • To provide a framework for optimal dose selection of novel cancer therapeutics.

Main Methods:

  • A Bayesian model-based design incorporating a bivariate Gaussian latent variable.
  • Modeling monotonic toxicity and quadratic activity dose-response curves.
  • Utilizing predictive distributions for dose recommendation and uncertainty quantification.

Main Results:

  • The proposed design effectively balances toxicity and activity assessments.
  • It allows for incorporation of prior information through a Bayesian framework.
  • Comparison with existing methods demonstrates potential advantages in dose selection.

Conclusions:

  • The novel model-based design offers a robust approach for early-phase oncology dose escalation.
  • Integrating safety and activity improves decision-making for molecular targeted agents.
  • This approach can enhance the efficiency and success rates of early clinical development.
Keywords:
Adaptive designBayesiandose findingefficacysafety

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