Group-by-Treatment Interaction Effects in Comparative Bioavailability Studies

Bibliographic Details
Title: Group-by-Treatment Interaction Effects in Comparative Bioavailability Studies
Authors: Helmut Schütz, Divan A. Burger, Erik Cobo, David D. Dubins, Tibor Farkás, Detlew Labes, Benjamin Lang, Jordi Ocaña, Arne Ring, Anastasia Shitova, Volodymyr Stus, Michael Tomashevskiy
Contributors: Universitat Politècnica de Catalunya. Departament d'Estadística i Investigació Operativa, Universitat Politècnica de Catalunya. GRBIO - Grup de Recerca en Bioestadística i Bioinformàtica
Source: UPCommons. Portal del coneixement obert de la UPC
Universitat Politècnica de Catalunya (UPC)
Publisher Information: Springer Science and Business Media LLC, 2024.
Publication Year: 2024
Subject Terms: Biometry, Biomatemàtica, Classificació AMS::62 Statistics::62D05 Sampling theory, sample surveys, Biological Availability, Classificació AMS::92 Biology and other natural sciences::92B Mathematical biology in general, regulatory guidelines, Monte-Carlo simulations, Cross-Over Studies [MeSH], Humans [MeSH], group-by-treatment interaction, average bioequivalence, Biological Availability [MeSH], Research Design [MeSH], Research Article, 01 natural sciences, Classificació AMS::62 Statistics::62P Applications, sample surveys, 03 medical and health sciences, 0302 clinical medicine, Classificació AMS::62 Statistics::62D05 Sampling theory, Humans, Sampling (Statistics), 0101 mathematics, Group-by-treatment interaction, Biomathematics, Biometria, Cross-Over Studies, Average bioequivalence, Àrees temàtiques de la UPC::Matemàtiques i estadística::Matemàtica aplicada a les ciències, Research Design, Regulatory guidelines, Mostreig (Estadística)
Description: Comparative bioavailability studies often involve multiple groups of subjects for a variety of reasons, such as clinical capacity limitations. This raises questions about the validity of pooling data from these groups in the statistical analysis and whether a group-by-treatment interaction should be evaluated. We investigated the presence or absence of group-by-treatment interactions through both simulation techniques and a meta-study of well-controlled trials. Our findings reveal that the test falsely detects an interaction when no true group-by-treatment interaction exists. Conversely, when a true group-by-treatment interaction does exist, it often goes undetected. In our meta-study, the detected group-by-treatment interactions were observed at approximately the level of the test and, thus, can be considered false positives. Testing for a group-by-treatment interaction is both misleading and uninformative. It often falsely identifies an interaction when none exists and fails to detect a real one. This occurs because the test is performed between subjects in crossover designs, and studies are powered to compare treatments within subjects. This work demonstrates a lack of utility for including a group-by-treatment interaction in the model when assessing single-site comparative bioavailability studies, and the clinical trial study structure is divided into groups. Graphical Abstract
Document Type: Article
File Description: application/pdf
Language: English
ISSN: 1550-7416
DOI: 10.1208/s12248-024-00921-x
Access URL: https://pubmed.ncbi.nlm.nih.gov/38632178
https://hdl.handle.net/2117/409494
https://doi.org/10.1208/s12248-024-00921-x
https://repository.publisso.de/resource/frl:6508400
Rights: CC BY
Accession Number: edsair.doi.dedup.....abc4964d28fcbd79e5f2129761bdbe8e
Database: OpenAIRE
Description
ISSN:15507416
DOI:10.1208/s12248-024-00921-x