| Affiliation: | 1.Centre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences,University of Oxford,Oxford,UK;2.Oncology Clinical Trials Office (OCTO), Department of Oncology,University of Oxford,Oxford,UK;3.CRUK MRC Oxford Institute for Radiation Oncology, Gray Laboratories,University of Oxford,Oxford,UK |
| Abstract: | BackgroundFor a clinical trials unit to run its first model-based, phase I trial, the statistician, chief investigator, and trial manager must all acquire a new set of skills. These trials also require a different approach to funding and data collection.Challenges and discussionFrom the statisticians’ viewpoint, we highlight what is needed to move from running rule-based, early-phase trials to running a model-based phase I study as we experienced it in our trials unit located in the United Kingdom. Our example is CHARIOT, a dose-finding trial using the time-to-event continual reassessment method. It consists of three stages and aims to discover the maximum tolerated dose of the combination of radiotherapy, chemotherapy, and the ataxia telangiectasia mutated Rad3-related inhibitor M6620 (previously known as VX-970) in patients with oesophageal cancer. We present the challenges we faced in designing this trial and how we overcame them as a way of demystifying the conduct of a model-based trial in a grant-funded clinical trials unit.ConclusionsAlthough we appreciate that undertaking model-based trials requires additional time and effort, they are feasible to implement and, once suitable tools such as guiding publications and document templates become available, the design and set-up process will be easier and more efficient. |
