Challenges in implementing model-based phase I designs in a grant-funded clinical trials unit.

Eleni Frangou
Eleni Frangou
General Hospital of Athens
Jane Holmes
Jane Holmes
University of Wales College of Medicine
Sharon Love
Sharon Love
St Thomas's Hospital
United Kingdom
Maria Hawkins
Maria Hawkins
Princess Margaret Hospital

Trials 2017 Dec 28;18(1):620. Epub 2017 Dec 28.

CRUK MRC Oxford Institute for Radiation Oncology, Gray Laboratories, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford, OX3 7DQ, UK.

Background: For 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 Discussion: From 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.

Conclusions: Although 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.

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December 2017
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