Unit:
Κατεύθυνση Ανάπτυξη Νέων Φαρμάκων: Έρευνα, Κυκλοφορία και ΠρόσβασηLibrary of the School of Health Sciences
Author:
Roumana Evangelia
Supervisors info:
Ευάγγελος Καραλής, Επίκουρος Καθηγητής, Τμήμα Φαρμακευτικής, ΕΚΠΑ
Κωνσταντίνος Ν. Συρίγος, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Ηλίας Κοττέας, Αναπληρωτής Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Original Title:
Μοντελοποίηση και προσομοιώσεις για την βελτιστοποίηση σχημάτων δειγματοληψίας σε μελέτες ΒιοΪσοδυναμίας
Translated title:
Modeling and simulation for the optimization of sampling schedule in Bioequivalence studies
Summary:
Bioequivalence (BE) studies are comparative bioavailability studies based on the fact that the therapeutic profile of a product is a function of the concentration of the active pharmaceutical ingredient at the site of action. BE studies form the required basis for regulatory approval of generic drugs. The reliability of the results of a BE study is influenced by the design of the study. Among other factors, the importance of the sampling design of a BE study is widely recognized, as inadequate sampling designs can lead to study inaccuracies and uncertain results, while a very dense sampling design can increase the workload, the cost of the study, and most importantly, the inconvenience to participants. In recent decades, there has been an increasing use of modeling and simulation in the field of bioequivalence. In Silico Clinical Trials (ISCT) have proven to be very useful for various aspects of bioequivalence assessment, including determining the sampling design. The aim of the present work is to evaluate the impact of differences in sampling schedule on bioequivalence outcome using modeling and simulation, i.e., in silico clinical trials. For this purpose, the design of a bioequivalence study performed in vivo is used as a target scenario. Several scenarios are created by changing the sample size, sampling design, Between-Subject Variability (BSV) and similarity of absorption rate of test and reference product. The simulations are performed in a computer program developed in Matlab® 2018b and the power of the study and GMR for the pharmacokinetic parameters Cmax and AUC are evaluated for each scenario. The results of the simulations showed that less dense and shorter sampling schedules did not significantly affect the power of the study and the GMR for the two pharmacokinetic parameters. In addition, the ISCTs proved to be very helpful in investigating and determining the clinical design parameters in a BE study.
Main subject category:
Health Sciences
Keywords:
Bioequivalence, Bioavailability, Donepezil, Sampling scheme, Sampling scedule, Sample size, Absorption, Cmax, AUC, Modeling, Simulation, In silico, Variability
