Statistics Surveys

Adaptive clinical trial designs for phase I cancer studies

Oleksandr Sverdlov, Weng Kee Wong, and Yevgen Ryeznik

Full-text: Open access

Abstract

Adaptive clinical trials are becoming increasingly popular research designs for clinical investigation. Adaptive designs are particularly useful in phase I cancer studies where clinical data are scant and the goals are to assess the drug dose-toxicity profile and to determine the maximum tolerated dose while minimizing the number of study patients treated at suboptimal dose levels.

In the current work we give an overview of adaptive design methods for phase I cancer trials. We find that modern statistical literature is replete with novel adaptive designs that have clearly defined objectives and established statistical properties, and are shown to outperform conventional dose finding methods such as the 3+3 design, both in terms of statistical efficiency and in terms of minimizing the number of patients treated at highly toxic or nonefficacious doses. We discuss statistical, logistical, and regulatory aspects of these designs and present some links to non-commercial statistical software for implementing these methods in practice.

Article information

Source
Statist. Surv., Volume 8 (2014), 2-44.

Dates
First available in Project Euclid: 29 May 2014

Permanent link to this document
https://projecteuclid.org/euclid.ssu/1401369114

Digital Object Identifier
doi:10.1214/14-SS106

Mathematical Reviews number (MathSciNet)
MR3216028

Zentralblatt MATH identifier
1295.82023

Subjects
Primary: 62L05: Sequential design 62L10: Sequential analysis 62L12: Sequential estimation
Secondary: 62L20: Stochastic approximation

Keywords
Bayesian designs “best intention” designs continual reassessment method dose finding studies estimation efficiency ethics maximum tolerated dose oncology trial designs optimal designs phase I stochastic approximation toxicity up-and-down designs

Citation

Sverdlov, Oleksandr; Wong, Weng Kee; Ryeznik, Yevgen. Adaptive clinical trial designs for phase I cancer studies. Statist. Surv. 8 (2014), 2--44. doi:10.1214/14-SS106. https://projecteuclid.org/euclid.ssu/1401369114


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