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Model-based bioequivalence approach for sparse pharmacokinetic bioequivalence studies: Model selection or model averaging?
Philipp, Morgane; Tessier, Adrien; Donnelly, Mark; Fang, Lanyan; Feng, Kairui; Zhao, Liang; Grosser, Stella; Sun, Guoying; Sun, Wanjie; Mentré, France; Bertrand, Julie.
Afiliación
  • Philipp M; Université Paris Cité, IAME, INSERM, Paris, France.
  • Tessier A; Clinical Pharmacometrics, Quantitative Pharmacology, Servier, Suresnes, France.
  • Donnelly M; Division of Quantitative Methods and Modeling, Office of Research and Standards, Office of Generic Drugs, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, USA.
  • Fang L; Division of Quantitative Methods and Modeling, Office of Research and Standards, Office of Generic Drugs, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, USA.
  • Feng K; Division of Quantitative Methods and Modeling, Office of Research and Standards, Office of Generic Drugs, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, USA.
  • Zhao L; Division of Quantitative Methods and Modeling, Office of Research and Standards, Office of Generic Drugs, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, USA.
  • Grosser S; Office of Biostatistics, Office of Translational Sciences, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, USA.
  • Sun G; Office of Biostatistics, Office of Translational Sciences, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, USA.
  • Sun W; Office of Biostatistics, Office of Translational Sciences, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, USA.
  • Mentré F; Université Paris Cité, IAME, INSERM, Paris, France.
  • Bertrand J; Université Paris Cité, IAME, INSERM, Paris, France.
Stat Med ; 43(18): 3403-3416, 2024 Aug 15.
Article en En | MEDLINE | ID: mdl-38847215
ABSTRACT
Conventional pharmacokinetic (PK) bioequivalence (BE) studies aim to compare the rate and extent of drug absorption from a test (T) and reference (R) product using non-compartmental analysis (NCA) and the two one-sided test (TOST). Recently published regulatory guidance recommends alternative model-based (MB) approaches for BE assessment when NCA is challenging, as for long-acting injectables and products which require sparse PK sampling. However, our previous research on MB-TOST approaches showed that model misspecification can lead to inflated type I error. The objective of this research was to compare the performance of model selection (MS) on R product arm data and model averaging (MA) from a pool of candidate structural PK models in MBBE studies with sparse sampling. Our simulation study was inspired by a real case BE study using a two-way crossover design. PK data were simulated using three structural models under the null hypothesis and one model under the alternative hypothesis. MB-TOST was applied either using each of the five candidate models or following MS and MA with or without the simulated model in the pool. Assuming T and R have the same PK model, our simulation shows that following MS and MA, MB-TOST controls type I error rates at or below 0.05 and attains similar or even higher power than when using the simulated model. Thus, we propose to use MS prior to MB-TOST for BE studies with sparse PK sampling and to consider MA when candidate models have similar Akaike information criterion.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Simulación por Computador / Equivalencia Terapéutica / Modelos Estadísticos / Estudios Cruzados Límite: Humans Idioma: En Revista: Stat Med Año: 2024 Tipo del documento: Article País de afiliación: Francia Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Simulación por Computador / Equivalencia Terapéutica / Modelos Estadísticos / Estudios Cruzados Límite: Humans Idioma: En Revista: Stat Med Año: 2024 Tipo del documento: Article País de afiliación: Francia Pais de publicación: Reino Unido