Use this URL to cite or link to this record in EThOS:
Title: Group sequential and adaptive methods : topics with applications for clinical trials
Author: Öhrn, Carl Fredrik
ISNI:       0000 0004 2707 8246
Awarding Body: University of Bath
Current Institution: University of Bath
Date of Award: 2011
Availability of Full Text:
Access from EThOS:
Access from Institution:
This thesis deals with sequential and adaptive methods for clinical trials, and how such methods can be used to achieve efficient clinical trial designs. The efficiency gains that can be achieved through non-adaptive group sequential methods are well established, while the newer adaptive methods seek to combine the best of the classical group sequential framework with an approach that gives increased flexibility. Our results show that the adaptive methods can provide some additional efficiency, as well as increased possibilities to respond to new internal and external information. Care is however needed when applying adaptive methods. While sub-optimal rules for adaptation can lead to inefficiencies, the logistical challenges can also be considerable. Efficient non-adaptive group sequential designs are often easier to implement in practice, and have for the cases we have considered been quite competitive in terms of efficiency. The four problems that are presented in this thesis are very relevant to how clinical trials are run in practice. The solutions that we present are either new approaches to problems that have not previously been solved, or methods that are more efficient than the ones currently available in the literature. Several challenging optimisation problems are solved through numerical computations. The optimal designs that are achieved can be used to benchmark new methods proposed in this thesis as well as methods available in the statistical literature. The problem that is solved in Chapter 5 can be viewed as a natural extension to the other problems. It brings together methods that we have used to the design of individual trials, to solve the more complex problem of designing a sequence of trials that are the core part of a clinical development program. The expected utility that is maximised is motivated by how the development of new medicines works in practice.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: group sequential ; decision analysis ; Adaptive ; optimality ; clinical trials