Developments to established dose-finding methodologies for application in trials with complex and innovative designs

Patel, Amit (2024). Developments to established dose-finding methodologies for application in trials with complex and innovative designs. University of Birmingham. Ph.D.

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Abstract

The results and decisions made in early phase clinical trials play an important role in the drug development process. Failure to make correct or accurate decisions may result in further unwarranted clinical research and may also cause potential future harm to patients.

This thesis explores methodologies used in dose-finding trials, specifically looking at the implementation of these methods and how they can be extended to answer different questions and assist with decision-making.

Firstly we detail our experiences implementing a novel methodology for a dose-finding trial where monotonic ordering is not possible. We then present an extension to a seamless adaptive phase I/II trial design which aims to conduct dose-finding and replace the need for a randomised phase II trial.

We also present two extensions to dose transition pathways, a visualisation tool to aid designing and decision making in early phase trials. The first looks at how they can be applied to more complex time-to-event methodologies and the second looks at how the same concept can be applied to single-arm phase II trials.

Throughout this thesis we include exemplar trials and showcase our methods being motivated or implemented into clinical trials conducted by the Cancer Research UK Clinical Trials Unit at the University of Birmingham.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):