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Optimal sequential designs in phase I studies

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  • Azriel, David

Abstract

Phase I clinical trials are conducted in order to find the maximum tolerated dose of a given drug out of a set of doses, usually finite. In general, once a formal target function and a suitable probability structure are defined, optimization of sequential studies can theoretically be achieved using backward induction. This is a computationally heavy task and most of the proposed methods can be regarded as “myopic” strategies with respect to a certain loss function. Such designs are computationally feasible, but are not globally optimal. A Dynamic Programming algorithm that overcomes such computational difficulties is presented. It computes the global optimal designs with respect to different loss functions, which represent different purposes of a phase I study. Though the optimal designs provide an improvement over the standard designs, the improvement is not very significant. The expected loss of the global optimal design is about 3% (at most) less than in the “myopic” policies in the specific probability structure that have been considered. This is important as computationally feasible and simple algorithms provide designs that are very close to being optimal.

Suggested Citation

  • Azriel, David, 2014. "Optimal sequential designs in phase I studies," Computational Statistics & Data Analysis, Elsevier, vol. 71(C), pages 288-297.
    • Handle: RePEc:eee:csdana:v:71:y:2014:i:c:p:288-297
    DOI: 10.1016/j.csda.2013.05.010
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    References listed on IDEAS

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    1. Drovandi, Christopher C. & McGree, James M. & Pettitt, Anthony N., 2013. "Sequential Monte Carlo for Bayesian sequentially designed experiments for discrete data," Computational Statistics & Data Analysis, Elsevier, vol. 57(1), pages 320-335.
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    4. Azriel, David, 2012. "A note on the robustness of the continual reassessment method," Statistics & Probability Letters, Elsevier, vol. 82(5), pages 902-906.
    5. Oron Assaf P. & Azriel David & Hoff Peter D., 2011. "Dose-Finding Designs: The Role of Convergence Properties," The International Journal of Biostatistics, De Gruyter, vol. 7(1), pages 1-17, October.
    6. Ying Kuen Cheung & Rick Chappell, 2002. "A Simple Technique to Evaluate Model Sensitivity in the Continual Reassessment Method," Biometrics, The International Biometric Society, vol. 58(3), pages 671-674, September.
    7. David Azriel & Micha Mandel & Yosef Rinott, 2010. "The Treatment Versus Experimentation Dilemma in Dose-finding Studies," Discussion Paper Series dp559, The Federmann Center for the Study of Rationality, the Hebrew University, Jerusalem.
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