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Factorial versus multi‐arm multi‐stage designs for clinical trials with multiple treatments
Author(s) -
Jaki Thomas,
Vasileiou Despina
Publication year - 2016
Publication title -
statistics in medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.996
H-Index - 183
eISSN - 1097-0258
pISSN - 0277-6715
DOI - 10.1002/sim.7159
Subject(s) - type i and type ii errors , factorial , factorial experiment , sample size determination , statistics , fractional factorial design , statistical power , research design , design of experiments , mathematics , computer science , clinical study design , optimal design , clinical trial , medicine , mathematical analysis , pathology
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. © 2016 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd.