Sample size/power calculations for repeated ordinal measurements in population pharmacodynamic experiments
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Population pharmacodynamic experiments sometime involve repeated measurements of ordinal random variables at specific time points. Such longitudinal data presents a challenge during modelling due to correlation between measurements within an individual and often mixed-effects modelling approach may be used for the analysis. It is important that these studies are adequately powered by including an adequate number of subjects in order to detect a significant treatment effect. This paper describes a method for calculating sample size for repeated ordinal measurements in population pharmacodynamic experiments based on analysis by a mixed-effects modelling approach. The Wald test is used for testing the significance of treatment effects. This method is fast, simple and efficient. It can also be extended to account for differential allocation of subjects to the groups and unbalanced sampling designs between and within groups. The results obtained from two simulation studies using nonlinear mixed-effects modelling software (NONMEM) showed good agreement between the power obtained from simulation and nominal power used for sample size calculations.
KeywordsOrdinal measurements Sample size Power Ordered categorical Cumulative logit Population pharmacodynamics Mixed-effects modelling Clinical trials
The research was sponsored by the Centre for Applied Pharmacokinetic Research, School of Pharmacy and Pharmaceutical Sciences, The University of Manchester, Manchester, UK. (CAPKR is supported by the following consortium members; Eli Lilly, GlaxoSmithKline, Novartis, Pfizer and Servier).
- 3.McCullagh P, Nelder JA (1989) Generalized linear models. Chapman and Hall, LondonGoogle Scholar
- 8.Beal SL, Sheiner LB (1992) NONMEM users guides, parts I-VII. NONMEM project group. University of California, San FranciscoGoogle Scholar
- 21.S-PLUS (2007) Function guide. Insightful Corporation, Seattle, WAGoogle Scholar
- 22.AB MATL (2008) Function reference. The MathWorks Inc., Natick, MAGoogle Scholar
- 23.Gabrielsson J, Weiner D (2000) Pharmacokinetic & pharmacodynamic data analysis: concept and applications, vol 4. Swedish Pharmaceutical Press, Stockholm, SwedenGoogle Scholar
- 24.Laurijssens B, Krause A, Harnisch L (2008) Model-based analysis of a longitudinal binary response as the primary analysis for a phase II study in migraine prophylaxis. PAGE abstracts of the annual meeting of the population approach group in Europe 17 Abstr 1275Google Scholar