Comparison of Estimation Methods in NONMEM 7.2: Application to a Real Clinical Trial Dataset

실제 임상 데이터를 이용한 NONMEM 7.2에 도입된 추정법 비교 연구

  • Yun, Hwi-Yeol (Department of Pharmaceutical biosciences, Uppsala University) ;
  • Chae, Jung-Woo (Department of Pharmacy, Chungnam National University) ;
  • Kwon, Kwang-Il (Department of Pharmacy, Chungnam National University)
  • 윤휘열 (웁살라 대학교 약학-생명과학대학 약물계량학 그룹) ;
  • 채정우 (충남대학교 약학대학 임상약학연구실) ;
  • 권광일 (충남대학교 약학대학 임상약학연구실)
  • Received : 2013.03.25
  • Accepted : 2013.05.22
  • Published : 2013.06.30

Abstract

Purpose: This study compared the performance of new NONMEM estimation methods using a population analysis dataset collected from a clinical study that consisted of 40 individuals and 567 observations after a single oral dose of glimepiride. Method: The NONMEM 7.2 estimation methods tested were first-order conditional estimation with interaction (FOCEI), importance sampling (IMP), importance sampling assisted by mode a posteriori (IMPMAP), iterative two stage (ITS), stochastic approximation expectation-maximization (SAEM), and Markov chain Monte Carlo Bayesian (BAYES) using a two-compartment open model. Results: The parameters estimated by IMP, IMPMAP, ITS, SAEM, and BAYES were similar to those estimated using FOCEI, and the objective function value (OFV) for diagnosing the model criteria was significantly decreased in FOCEI, IMPMAP, SAEM, and BAYES in comparison with IMP. Parameter precision in terms of the estimated standard error was estimated precisely with FOCEI, IMP, IMPMAP, and BAYES. The run time for the model analysis was shortest with BAYES. Conclusion: In conclusion, the new estimation methods in NONMEM 7.2 performed similarly in terms of parameter estimation, but the results in terms of parameter precision and model run times using BAYES were most suitable for analyzing this dataset.

Keywords

References

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