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Rapid Sample Size Calculations for a Defined Likelihood Ratio Test-Based Power in Mixed-Effects Models

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Abstract

Efficient power calculation methods have previously been suggested for Wald test-based inference in mixed-effects models but the only available alternative for Likelihood ratio test-based hypothesis testing has been to perform computer-intensive multiple simulations and re-estimations. The proposed Monte Carlo Mapped Power (MCMP) method is based on the use of the difference in individual objective function values (ΔiOFV) derived from a large dataset simulated from a full model and subsequently re-estimated with the full and reduced models. The ΔiOFV is sampled and summed (∑ΔiOFVs) for each study at each sample size of interest to study, and the percentage of ∑ΔiOFVs greater than the significance criterion is taken as the power. The power versus sample size relationship established via the MCMP method was compared to traditional assessment of model-based power for six different pharmacokinetic and pharmacodynamic models and designs. In each case, 1,000 simulated datasets were analysed with the full and reduced models. There was concordance in power between the traditional and MCMP methods such that for 90% power, the difference in required sample size was in most investigated cases less than 10%. The MCMP method was able to provide relevant power information for a representative pharmacometric model at less than 1% of the run-time of an SSE. The suggested MCMP method provides a fast and accurate prediction of the power and sample size relationship.

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Acknowledgement

We would like to acknowledge Kajsa Harling for computational assistance.

Conflict of interest

The authors declared no conflict of interest.

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Authors and Affiliations

  1. Department of Pharmaceutical Biosciences, Uppsala University, Box 591, 75124, Uppsala, Sweden

    Camille Vong, Martin Bergstrand, Joakim Nyberg & Mats O. Karlsson

Authors
  1. Camille Vong
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  2. Martin Bergstrand
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  3. Joakim Nyberg
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  4. Mats O. Karlsson
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Correspondence to Camille Vong.

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Vong, C., Bergstrand, M., Nyberg, J. et al. Rapid Sample Size Calculations for a Defined Likelihood Ratio Test-Based Power in Mixed-Effects Models. AAPS J 14, 176–186 (2012). https://doi.org/10.1208/s12248-012-9327-8

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  • DOI: https://doi.org/10.1208/s12248-012-9327-8

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