2026-04-13T04:32:05Zhttps://recercat.cat/oai/requestoai:recercat.cat:2117/1143952026-02-02T09:58:08Zcom_2072_1033col_2072_452950
RECERCAT
author
Molins Lleonart, Eduard
author
Cobo Valeri, Erik
author
Ocaña Rebull, Jordi
2017-12
This is the peer reviewed version of the following article: Molins, E., Cobo, E., Ocaña, J. Two-stage designs versus European scaled average designs in bioequivalence studies for highly variable drugs: which to choose?. "Statistics in medicine", Desembre 2017, vol. 36, núm. 30, p. 4777-4788, which has been published in final form at http://onlinelibrary.wiley.com/doi/10.1002/sim.7452/pdf. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.The usual approach to determine bioequivalence for highly variable drugs is scaled average bioequivalence, which is based on expanding the limits as a function of the within-subject variability in the reference formulation. This requires separately estimating this variability and thus using replicated or semireplicated crossover designs. On the other hand, regulations also allow using common 2 × 2 crossover designs based on two-stage adaptive approaches with sample size reestimation at an interim analysis. The choice between scaled or two-stage designs is crucial and must be fully described in the protocol. Using Monte Carlo simulations, we show that both methodologies achieve comparable statistical power, though the scaled method usually requires less sample size, but at the expense of each subject being exposed more times to the treatments. With an adequate initial sample size (not too low, eg, 24 subjects), two-stage methods are a flexible and efficient option to consider: They have enough power (eg, 80%) at the first stage for non-highly variable drugs, and, if otherwise, they provide the opportunity to step up to a second stage that includes additional subjects.Peer ReviewedPostprint (author's final draft)
Open Access
Àrees temàtiques de la UPC::Matemàtiques i estadística::Anàlisi numèrica::Modelització matemàtica
Àrees temàtiques de la UPC::Matemàtiques i estadística::Anàlisi numèrica
Àrees temàtiques de la UPC::Matemàtiques i estadística::Matemàtica aplicada a les ciències
Numerical analysis--Simulation methods
Numerical analysis
Biomathematics
Average Bioequivalence (ABE)
Reference Scaled Average Bioequivalence (RSABE)
Two-Stage Designs (TSD)
Highly Variable Drugs (HVD)
Significance Level Adjustment
Anàlisi numèrica -- Processament de dades
Anàlisi numèrica
Biomatemàtica
Classificació AMS::65 Numerical analysis::65C Probabilistic methods, simulation and stochastic differential equations
Classificació AMS::65 Numerical analysis::65K Mathematical programming, optimization and variational techniques
Classificació AMS::92 Biology and other natural sciences::92B Mathematical biology in general
Two-stage designs versus European scaled average designs in bioequivalence studies for highly variable drugs: which to choose?
Article