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On Optimal Designs for Clinical Trials: An Updated Review

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Abstract

Optimization of clinical trial designs can help investigators achieve higher quality results for the given resource constraints. The present paper gives an overview of optimal designs for various important problems that arise in different stages of clinical drug development, including phase I dose–toxicity studies; phase I/II studies that consider early efficacy and toxicity outcomes simultaneously; phase II dose–response studies driven by multiple comparisons (MCP), modeling techniques (Mod), or their combination (MCP–Mod); phase III randomized controlled multi-arm multi-objective clinical trials to test difference among several treatment groups; and population pharmacokinetics–pharmacodynamics experiments. We find that modern literature is very rich with optimal design methodologies that can be utilized by clinical researchers to improve efficiency of drug development.

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Acknowledgements

The authors would like to thank three anonymous reviewers for their constructive comments that have helped improve the original version of the manuscript. Wong was partially supported by a grant from the National Institute of General Medical Sciences of the National Institutes of Health under Award Number R01GM107639. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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Authors and Affiliations

  1. Early Development Biostatistics, Novartis Pharmaceuticals, East Hanover, USA

    Oleksandr Sverdlov

  2. Department of Mathematics, Uppsala University, Uppsala, Sweden

    Yevgen Ryeznik

  3. Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden

    Yevgen Ryeznik

  4. Department of Biostatistics, Fielding School of Public Health, University of California, Los Angeles, USA

    Weng Kee Wong

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  1. Oleksandr Sverdlov
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Part of special issue guest edited by Pritam Ranjan and Min Yang--- Algorithms, Analysis and Advanced Methodologies in the Design of Experiments.

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Sverdlov, O., Ryeznik, Y. & Wong, W.K. On Optimal Designs for Clinical Trials: An Updated Review. J Stat Theory Pract 14, 10 (2020). https://doi.org/10.1007/s42519-019-0073-4

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