Autor(en): | Loingeville, Florence Bertrand, Julie Nguyen, Thu Thuy Sharan, Satish Feng, Kairui Sun, Wanjie Han, Jing Grosser, Stella Zhao, Liang Fang, Lanyan Möllenhoff, Kathrin Dette, Holger Mentré, France |
Titel: | New model-based bioequivalence statistical approaches for pharmacokinetic studies with sparse sampling |
Sprache (ISO): | en |
Zusammenfassung: | In traditional pharmacokinetic (PK) bioequivalence analysis, two one-sided tests (TOST) are conducted on the area under the concentration-time curve and the maximal concentration derived using a non-compartmental approach. When rich sampling is unfeasible, a model-based (MB) approach, using nonlinear mixed effect models (NLMEM) is possible. However, MB-TOST using asymptotic standard errors (SE) presents increased type I error when asymptotic conditions do not hold. Methods : In this work, we propose three alternative calculations of the SE based on i) an adaptation to NLMEM of the correction proposed by Gallant, ii) the a posteriori distribution of the treatment coefficient using the Hamiltonian Monte Carlo algorithm, and iii) parametric random effects and residual errors bootstrap. We evaluate these approaches by simulations, for two-arms parallel and two-periods two-sequences cross-over design with rich (n=10) and sparse (n=3) sampling under the null and the alternative hypotheses, with MB-TOST. Results: All new approaches correct for the in ation of MB-TOST type I error in PK studies with sparse designs. The approach based on the a posteriori distribution appears to be the best compromise between controlled type I errors and computing times. Conclusion: MB-TOST using non-asymptotic SE controls type I error rate better than when using asymptotic SE estimates for bioequivalence on PK studies with sparse sampling. |
Schlagwörter: | pharmacokinetics non-asymptotic standard error two 21 one-sided tests nonlinear mixed effects model bioequivalence |
URI: | http://hdl.handle.net/2003/39208 http://dx.doi.org/10.17877/DE290R-21125 |
Erscheinungsdatum: | 2020 |
Enthalten in den Sammlungen: | Sonderforschungsbereich (SFB) 823 |
Dateien zu dieser Ressource:
Datei | Beschreibung | Größe | Format | |
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DP_1920_SFB823_Loingeville_Bertrand_Nguyen_Sharan_Feng_Dette_etal..pdf | DNB | 481.36 kB | Adobe PDF | Öffnen/Anzeigen |
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