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One- and two-stage design proposals for a phase II trial comparing three active treatments with control using an ordered categorical endpoint.

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One- and two-stage design proposals for a phase II trial comparing three active treatments with control using an ordered categorical endpoint. / Whitehead, John; Jaki, Thomas.
In: Statistics in Medicine, Vol. 28, No. 5, 28.02.2009, p. 828-847.

Research output: Contribution to Journal/Magazine › Journal article › peer-review

Harvard

Whitehead, J & Jaki, T 2009, 'One- and two-stage design proposals for a phase II trial comparing three active treatments with control using an ordered categorical endpoint.', Statistics in Medicine, vol. 28, no. 5, pp. 828-847. https://doi.org/10.1002/sim.3508

APA

Whitehead, J., & Jaki, T. (2009). One- and two-stage design proposals for a phase II trial comparing three active treatments with control using an ordered categorical endpoint. Statistics in Medicine, 28(5), 828-847. https://doi.org/10.1002/sim.3508

Vancouver

Whitehead J, Jaki T. One- and two-stage design proposals for a phase II trial comparing three active treatments with control using an ordered categorical endpoint. Statistics in Medicine. 2009 Feb 28;28(5):828-847. doi: 10.1002/sim.3508

Author

Whitehead, John ; Jaki, Thomas. / One- and two-stage design proposals for a phase II trial comparing three active treatments with control using an ordered categorical endpoint. In: Statistics in Medicine. 2009 ; Vol. 28, No. 5. pp. 828-847.

Bibtex

@article{ae65b16504c848b49b9fa4795e1429e9,
title = "One- and two-stage design proposals for a phase II trial comparing three active treatments with control using an ordered categorical endpoint.",
abstract = "Phase II clinical trials are performed to investigate whether a novel treatment shows sufficient promise of efficacy to justify its evaluation in a subsequent definitive phase III trial, and they are often also used to select the dose to take forward. In this paper we discuss different design proposals for a phase II trial in which three active treatment doses and a placebo control are to be compared in terms of a single-ordered categorical endpoint. The sample size requirements for one-stage and two-stage designs are derived, based on an approach similar to that of Dunnett. Detailed computations are prepared for an illustrative example concerning a study in stroke. Allowance for early stopping for futility is made. Simulations are used to verify that the specified type I error and power requirements are valid, despite certain approximations used in the derivation of sample size. The advantages and disadvantages of the different designs are discussed, and the scope for extending the approach to different forms of endpoint is considered.",
keywords = "interim analysis , one-stage design, ordinal data , phase II trial , two-stage design",
author = "John Whitehead and Thomas Jaki",
year = "2009",
month = feb,
day = "28",
doi = "10.1002/sim.3508",
language = "English",
volume = "28",
pages = "828--847",
journal = "Statistics in Medicine",
issn = "1097-0258",
publisher = "John Wiley and Sons Ltd",
number = "5",

}

RIS

TY - JOUR

T1 - One- and two-stage design proposals for a phase II trial comparing three active treatments with control using an ordered categorical endpoint.

AU - Whitehead, John

AU - Jaki, Thomas

PY - 2009/2/28

Y1 - 2009/2/28

N2 - Phase II clinical trials are performed to investigate whether a novel treatment shows sufficient promise of efficacy to justify its evaluation in a subsequent definitive phase III trial, and they are often also used to select the dose to take forward. In this paper we discuss different design proposals for a phase II trial in which three active treatment doses and a placebo control are to be compared in terms of a single-ordered categorical endpoint. The sample size requirements for one-stage and two-stage designs are derived, based on an approach similar to that of Dunnett. Detailed computations are prepared for an illustrative example concerning a study in stroke. Allowance for early stopping for futility is made. Simulations are used to verify that the specified type I error and power requirements are valid, despite certain approximations used in the derivation of sample size. The advantages and disadvantages of the different designs are discussed, and the scope for extending the approach to different forms of endpoint is considered.

AB - Phase II clinical trials are performed to investigate whether a novel treatment shows sufficient promise of efficacy to justify its evaluation in a subsequent definitive phase III trial, and they are often also used to select the dose to take forward. In this paper we discuss different design proposals for a phase II trial in which three active treatment doses and a placebo control are to be compared in terms of a single-ordered categorical endpoint. The sample size requirements for one-stage and two-stage designs are derived, based on an approach similar to that of Dunnett. Detailed computations are prepared for an illustrative example concerning a study in stroke. Allowance for early stopping for futility is made. Simulations are used to verify that the specified type I error and power requirements are valid, despite certain approximations used in the derivation of sample size. The advantages and disadvantages of the different designs are discussed, and the scope for extending the approach to different forms of endpoint is considered.

KW - interim analysis

KW - one-stage design

KW - ordinal data

KW - phase II trial

KW - two-stage design

U2 - 10.1002/sim.3508

DO - 10.1002/sim.3508

M3 - Journal article

VL - 28

SP - 828

EP - 847

JO - Statistics in Medicine

JF - Statistics in Medicine

SN - 1097-0258

IS - 5

ER -