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Factorial versus multi-arm multi-stage designs for clinical trials with multiple treatments

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Factorial versus multi-arm multi-stage designs for clinical trials with multiple treatments. / Jaki, Thomas Friedrich; Vasileiou, Despoina.
In: Statistics in Medicine, Vol. 36, No. 4, 20.02.2017, p. 563-580.

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Jaki TF, Vasileiou D. Factorial versus multi-arm multi-stage designs for clinical trials with multiple treatments. Statistics in Medicine. 2017 Feb 20;36(4):563-580. Epub 2016 Nov 2. doi: 10.1002/sim.7159

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@article{eec1fe0d2df24a3b8aa874c3691147d8,
title = "Factorial versus multi-arm multi-stage designs for clinical trials with multiple treatments",
abstract = "When several treatments are available for evaluation in a clinical trial, different design options are available. We compare multi-arm multi-stage with factorial designs, and in particular, we will consider a 2 × 2 factorial design, where groups of patients will either take treatments A, B, both or neither. We investigate the performance and characteristics of both types of designs under different scenarios and compare them using both theory and simulations. For the factorial designs, we construct appropriate test statistics to test the hypothesis of no treatment effect against the control group with overall control of the type I error. We study the effect of the choice of the allocation ratios on the critical value and sample size requirements for a target power. We also study how the possibility of an interaction between the two treatments A and B affects type I and type II errors when testing for significance of each of the treatment effects. We present both simulation results and a case study on an osteoarthritis clinical trial. We discover that in an optimal factorial design in terms of minimising the associated critical value, the corresponding allocation ratios differ substantially to those of a balanced design. We also find evidence of potentially big losses in power in factorial designs for moderate deviations from the study design assumptions and little gain compared with multi-arm multi-stage designs when the assumptions hold.",
author = "Jaki, {Thomas Friedrich} and Despoina Vasileiou",
year = "2017",
month = feb,
day = "20",
doi = "10.1002/sim.7159",
language = "English",
volume = "36",
pages = "563--580",
journal = "Statistics in Medicine",
issn = "0277-6715",
publisher = "John Wiley and Sons Ltd",
number = "4",

}

RIS

TY - JOUR

T1 - Factorial versus multi-arm multi-stage designs for clinical trials with multiple treatments

AU - Jaki, Thomas Friedrich

AU - Vasileiou, Despoina

PY - 2017/2/20

Y1 - 2017/2/20

N2 - When several treatments are available for evaluation in a clinical trial, different design options are available. We compare multi-arm multi-stage with factorial designs, and in particular, we will consider a 2 × 2 factorial design, where groups of patients will either take treatments A, B, both or neither. We investigate the performance and characteristics of both types of designs under different scenarios and compare them using both theory and simulations. For the factorial designs, we construct appropriate test statistics to test the hypothesis of no treatment effect against the control group with overall control of the type I error. We study the effect of the choice of the allocation ratios on the critical value and sample size requirements for a target power. We also study how the possibility of an interaction between the two treatments A and B affects type I and type II errors when testing for significance of each of the treatment effects. We present both simulation results and a case study on an osteoarthritis clinical trial. We discover that in an optimal factorial design in terms of minimising the associated critical value, the corresponding allocation ratios differ substantially to those of a balanced design. We also find evidence of potentially big losses in power in factorial designs for moderate deviations from the study design assumptions and little gain compared with multi-arm multi-stage designs when the assumptions hold.

AB - When several treatments are available for evaluation in a clinical trial, different design options are available. We compare multi-arm multi-stage with factorial designs, and in particular, we will consider a 2 × 2 factorial design, where groups of patients will either take treatments A, B, both or neither. We investigate the performance and characteristics of both types of designs under different scenarios and compare them using both theory and simulations. For the factorial designs, we construct appropriate test statistics to test the hypothesis of no treatment effect against the control group with overall control of the type I error. We study the effect of the choice of the allocation ratios on the critical value and sample size requirements for a target power. We also study how the possibility of an interaction between the two treatments A and B affects type I and type II errors when testing for significance of each of the treatment effects. We present both simulation results and a case study on an osteoarthritis clinical trial. We discover that in an optimal factorial design in terms of minimising the associated critical value, the corresponding allocation ratios differ substantially to those of a balanced design. We also find evidence of potentially big losses in power in factorial designs for moderate deviations from the study design assumptions and little gain compared with multi-arm multi-stage designs when the assumptions hold.

U2 - 10.1002/sim.7159

DO - 10.1002/sim.7159

M3 - Journal article

VL - 36

SP - 563

EP - 580

JO - Statistics in Medicine

JF - Statistics in Medicine

SN - 0277-6715

IS - 4

ER -