A three-outcome design for phase II clinical trials

Daniel J. Sargent; Victor Chan; Richard M. Goldberg

doi:10.1016/S0197-2456(00)00115-X

A three-outcome design for phase II clinical trials

Daniel J. Sargent, Victor Chan, Richard M. Goldberg

Quantitative Health Sciences

Research output: Contribution to journal › Article › peer-review

60 Scopus citations

Abstract

The goal of a phase II trial is to make a preliminary determination regarding the activity and tolerability of a new treatment and thus to determine whether the treatment warrants further study in the phase III setting. Phase II clinical trials are typically designed in the hypothesis testing framework with two possible outcomes, either reject the null hypothesis H₀ or reject the alternative hypothesis H_a, based on the observed activity level. However, in cases where the observed activity is "borderline," the decision regarding the future of the agent is not as clear as the prespecified hypothesis test would indicate. In this paper we propose an alternative design that allows for three outcomes: reject H₀, reject H_a, or reject neither. We describe the theoretical properties of this design and illustrate it with several examples. We focus on the clinical implications of the three-outcome design.

Original language	English (US)
Pages (from-to)	117-125
Number of pages	9
Journal	Controlled Clinical Trials
Volume	22
Issue number	2
DOIs	https://doi.org/10.1016/S0197-2456(00)00115-X
State	Published - 2001

Keywords

Minimax design
Optimal design
Sequential testing

ASJC Scopus subject areas

Pharmacology

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10.1016/S0197-2456(00)00115-X

Cite this

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note = "Funding Information: This work was supported in part by grant CA-15083 from the National Cancer Institute. We thank Susan Geyer and two anonymous referees for comments that greatly improved the manuscript.",

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AU - Chan, Victor

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N2 - The goal of a phase II trial is to make a preliminary determination regarding the activity and tolerability of a new treatment and thus to determine whether the treatment warrants further study in the phase III setting. Phase II clinical trials are typically designed in the hypothesis testing framework with two possible outcomes, either reject the null hypothesis H0 or reject the alternative hypothesis Ha, based on the observed activity level. However, in cases where the observed activity is "borderline," the decision regarding the future of the agent is not as clear as the prespecified hypothesis test would indicate. In this paper we propose an alternative design that allows for three outcomes: reject H0, reject Ha, or reject neither. We describe the theoretical properties of this design and illustrate it with several examples. We focus on the clinical implications of the three-outcome design.

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KW - Optimal design

KW - Sequential testing

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A three-outcome design for phase II clinical trials

Abstract

Keywords

ASJC Scopus subject areas

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