Optimal design of clinical trials comparing several treatments with a control

Ian C. Marschner*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

17 Citations (Scopus)


Clinical trials are often designed to compare several treatments with a common control arm in pairwise fashion. In this paper we study optimal designs for such studies, based on minimizing the total number of patients required to achieve a given level of power. A common approach when designing studies to compare several treatments with a control is to achieve the desired power for each individual pairwise treatment comparison. However, it is often more appropriate to characterize power in terms of the family of null hypotheses being tested, and to control the probability of rejecting all, or alternatively any, of these individual hypotheses. While all approaches lead to unbalanced designs with more patients allocated to the control arm, it is found that the optimal design and required number of patients can vary substantially depending on the chosen characterization of power. The methods make allowance for both continuous and binary outcomes and are illustrated with reference to two clinical trials, one involving multiple doses compared to placebo and the other involving combination therapy compared to mono-therapies. In one example a 55% reduction in sample size is achieved through an optimal design combined with the appropriate characterization of power.

Original languageEnglish
Pages (from-to)23-33
Number of pages11
JournalPharmaceutical Statistics
Issue number1
Publication statusPublished - Jan 2007
Externally publishedYes


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