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

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.

Emotions in legal decisions: the construction of objective narratives in Italian criminal trials

Drawing on ethnographic data collected in Italian courts and prosecution offices, this dissertation offers new perspectives on legal decision-making by highlighting the importance of emotions for constructing and evaluating legal narratives. Focusing on criminal cases, it describes and dissects how judges and prosecutors use emotions in reflection and action tied to lay narratives and legal constraints. The analysis shows that legal professionals engage in different types of emotional dynamics when dealing with stories; first, they develop gut feelings, which are either endorsed or kept at distance by means of emotional reflexivity, to comply with legal ideals of objectivity and impartiality. Second, empathy emerges as a crucial tool to direct the interaction with lay people and to interpret legal prerequisites, such as credibility, and intent. Finally, the dissertation shows that lay stories lead legal professionals to become passionate and committed towards the correct application of the law, the restoration of the moral order, and the achievement of justice. In light of the empirical findings, this thesis strives to develop a theoretical understanding of legal decision-making as narrative work that includes emotional dynamics consistent with rational, objective action.