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Optimal designs for dose-response models with restricted design spaces

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  • Dette, Holger
  • Biedermann, Stefanie
  • Zhu, Wei

Abstract

In dose response studies, the dose range is often restricted due to concerns over drug toxicity and/or efficacy. We present restricted and unrestricted interval locally optimal designs with respect to a very general class of optimality criteria for estimating the underlying dose response curve. The underlying curve belongs to a diversified set of link functions suitable for the dose response studies and having a common canonical form. These include the fundamental binary response models – the logit and the probit as well as the skewed versions of these models. The results are illustrated through the re-design of a dose ranging trial conducted at the Merck Research Laboratories (Zeng and Zhu, 1997). This work is a generalization of the results of Dai and Zhu (2002) in terms of the design interval, the underlying dose response curve and the optimality criterion.

Suggested Citation

  • Dette, Holger & Biedermann, Stefanie & Zhu, Wei, 2004. "Optimal designs for dose-response models with restricted design spaces," Technical Reports 2004,40, Technische Universität Dortmund, Sonderforschungsbereich 475: Komplexitätsreduktion in multivariaten Datenstrukturen.
    • Handle: RePEc:zbw:sfb475:200440
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    1. Anthony Y. C. Kuk, 2004. "A litter‐based approach to risk assessment in developmental toxicity studies via a power family of completely monotone functions," Journal of the Royal Statistical Society Series C, Royal Statistical Society, vol. 53(2), pages 369-386, April.
    2. Linda M. Haines & Inna Perevozskaya & William F. Rosenberger, 2003. "Bayesian Optimal Designs for Phase I Clinical Trials," Biometrics, The International Biometric Society, vol. 59(3), pages 591-600, September.
    3. Holger Dette, 1997. "Designing Experiments with Respect to ‘Standardized’ Optimality Criteria," Journal of the Royal Statistical Society Series B, Royal Statistical Society, vol. 59(1), pages 97-110.
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    1. Dette, Holger & Biedermann, Stefanie & Zhu, Wei, 2005. "Compound Optimal Designs for Percentile Estimation in Dose-Response Models with Restricted Design Intervals," Technical Reports 2005,02, Technische Universität Dortmund, Sonderforschungsbereich 475: Komplexitätsreduktion in multivariaten Datenstrukturen.

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