Efficient treatment allocation in 2x2 multicenter trials when costs and variances are heterogeneous

Francesca Lemme*, Gerard J. P. van Breukelen, Math J. J. M. Candel

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


At the design stage of a study, it is crucial to compute the sample size needed for treatment effect estimation with maximum precision and power. The optimal design depends on the costs, which may be known at the design stage, and on the outcome variances, which are unknown. A balanced design, optimal for homogeneous costs and variances, is typically used. An alternative to the balanced design is a design optimal for the known and possibly heterogeneous costs, and homogeneous variances, called costs considering design. Both designs suffer from loss of efficiency, compared with optimal designs for heterogeneous costs and variances. For multicenter trials, we compute the relative efficiency of the balanced and the costs considering designs, relative to the optimal designs. We consider 2 heterogeneous costs and variance scenarios (in 1 scenario, 2 treatment conditions have small and 2 have large costs and variances; in the other scenario, 1 treatment condition has small, 2 have intermediate, and 1 has large costs and variances). Within these scenarios, we examine the relative efficiency of the balanced design and of the costs considering design as a function of the extents of heterogeneity of the costs and of the variances and of their congruence (congruent when the cheapest treatment has the smallest variance, incongruent when the cheapest treatment has the largest variance). We find that the costs considering design is generally more efficient than the balanced design, and we illustrate this theory on a multicenter trial on lifestyle improvement of patients in general practices.
Original languageEnglish
Pages (from-to)12-27
Number of pages16
JournalStatistics in Medicine
Issue number1
Publication statusPublished - 15 Jan 2018


  • 2x2 factorial design
  • balanced design
  • heterogeneous costs
  • heterogeneous variance
  • multicenter trial

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