Advisory Committee Chair
David T Redden
Advisory Committee Members
Christopher Coffey
Gary Cutter
Charles Katholi
David Kimberlin
Sharina Person
Document Type
Dissertation
Date of Award
2007
Degree Name by School
Doctor of Philosophy (PhD) School of Public Health
Abstract
Clinical trials to determine the usefulness of a new treatment are usually conducted in four (4) phases. Each phase is designed to answer a distinct research question about the usefulness of the new treatment. Phase I trials determine the safe dose range of the new treatment identify the possible side effects and other treatment associated toxicity issues, in a small group of healthy people. In phase II trials, the efficacy and safety of the new treatment is investigated in a larger group of individuals usually from the diseased population of interest. Phase III trials, conducted in large groups of people, further investigate the effectiveness of the new treatment, monitor its side effects, compare it to an established form of treatment for the disease and collect information that help determine the safe use of the new treatment. Phase IV trials, also called post marketing surveillance studies, are conducted after the treatment has been marketed to gather more information on the side effects in various subgroups and any side effects associated with long-term use. Several statistical designs have been proposed to answer the research questions posed at each phase. In the first paper of this dissertation, we propose a method for designing phase II trials that allows for early termination of the trial for lack of efficacy. The second paper, proposes a two-stage adaptive procedure for a phase III trial when there is statistical evidence that the effect of the treatment might differ depending on the characteristics of the individuals being investigated. The third paper, presents a iii modification of the two-stage adaptive procedure proposed in paper 2. The modified procedure allows for early termination of any stratum of the trial that shows little evidence of the treatment efficacy at the beginning of the second stage. A conditional power approach is implemented in all three designs to: 1) terminate early a trial or an arm of the trial due to lack of evidence of efficacy in papers 1 and 3 respectively; 2) control the type I error rate at the end of stage 2 conditioned on a statistically significant covariate by treatment interaction for the procedures proposed in papers 2 and 3.
Recommended Citation
Ayanlowo, Ayanbola Olajumoke, "Examination Of Novel Statistical Designs For Phase II And Phase III Clinical Trials" (2007). All ETDs from UAB. 3660.
https://digitalcommons.library.uab.edu/etd-collection/3660