Design of experiment in drug development: optimal allocations in multi-arm clinical trials and design space for multi-step processes

Frieri, Rosamarie (2021) Design of experiment in drug development: optimal allocations in multi-arm clinical trials and design space for multi-step processes, [Dissertation thesis], Alma Mater Studiorum Università di Bologna. Dottorato di ricerca in Scienze statistiche, 33 Ciclo.
Documenti full-text disponibili:
[img] Documento PDF (English) - Accesso riservato fino a 30 Giugno 2023 - Richiede un lettore di PDF come Xpdf o Adobe Acrobat Reader
Disponibile con Licenza: Salvo eventuali più ampie autorizzazioni dell'autore, la tesi può essere liberamente consultata e può essere effettuato il salvataggio e la stampa di una copia per fini strettamente personali di studio, di ricerca e di insegnamento, con espresso divieto di qualunque utilizzo direttamente o indirettamente commerciale. Ogni altro diritto sul materiale è riservato.
Download (2MB) | Contatta l'autore

Abstract

In this thesis, we deal with the design of experiments in the drug development process, focusing on the design of clinical trials for treatment comparisons (Part I) and the design of preclinical laboratory experiments for proteins development and manufacturing (Part II). In Part I we propose a multi-purpose design methodology for sequential clinical trials. We derived optimal allocations of patients to treatments for testing the efficacy of several experimental groups by also taking into account ethical considerations. We first consider exponential responses for survival trials and we then present a unified framework for heteroscedastic experimental groups that encompasses the general ANOVA set-up. The very good performance of the suggested optimal allocations, in terms of both inferential and ethical characteristics, are illustrated analytically and through several numerical examples, also performing comparisons with other designs proposed in the literature. Part II concerns the planning of experiments for processes composed of multiple steps in the context of preclinical drug development and manufacturing. Following the Quality by Design paradigm, the objective of the multi-step design strategy is the definition of the manufacturing design space of the whole process and, as we consider the interactions among the subsequent steps, our proposal ensures the quality and the safety of the final product, by enabling more flexibility and process robustness in the manufacturing.

Abstract
Tipologia del documento
Tesi di dottorato
Autore
Frieri, Rosamarie
Supervisore
Co-supervisore
Dottorato di ricerca
Ciclo
33
Coordinatore
Settore disciplinare
Settore concorsuale
Parole chiave
Optimal designs, Unequal allocations, ANOVA, Response Adaptive Randomisation, Multiple treatments, Wald test, Ethics, Survival trials, Design space, Multi-step processes
Data di discussione
26 Maggio 2021
URI

Altri metadati

Gestione del documento: Visualizza la tesi

^