Developing a Bayesian adaptive design for a phase I clinical trial: a case study for a novel HIV treatment
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
The design of phase I studies is often challenging, because of limited evidence to inform study protocols. Adaptive designs are now well established in cancer but much less so in other clinical areas. A phase I study to assess the safety, pharmacokinetic profile and antiretroviral efficacy of C34-PEG4-Chol, a novel peptide fusion inhibitor for the treatment of HIV infection, has been set up with Medical Research Council funding. During the study workup, Bayesian adaptive designs based on the continual reassessment method were compared with a more standard rule-based design, with the aim of choosing a design that would maximise the scientific information gained from the study. The process of specifying and evaluating the design options was time consuming and required the active involvement of all members of the trial's protocol development team. However, the effort was worthwhile as the originally proposed rule-based design has been replaced by a more efficient Bayesian adaptive design. While the outcome to be modelled, design details and evaluation criteria are trial specific, the principles behind their selection are general. This case study illustrates the steps required to establish a design in a novel context.
Date Issued
2016-11-27
Date Acceptance
2016-10-21
Citation
Statistics in Medicine, 2016, 36 (5), pp.754-771
ISSN
1097-0258
Publisher
Wiley
Start Page
754
End Page
771
Journal / Book Title
Statistics in Medicine
Volume
36
Issue
5
Copyright Statement
© 2016 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Identifier
http://www.ncbi.nlm.nih.gov/pubmed/27891651
Subjects
Science & Technology
Life Sciences & Biomedicine
Physical Sciences
Mathematical & Computational Biology
Public, Environmental & Occupational Health
Medical Informatics
Medicine, Research & Experimental
Statistics & Probability
Research & Experimental Medicine
Mathematics
Bayesian adaptive designs
dose-finding studies
continual reassessment method
fusion inhibitor
HIV clinical trials
phase I
CONTINUAL REASSESSMENT METHOD
DOSE-ESCALATION
FUSION INHIBITOR
CANCER
STROKE
COHORT
0104 Statistics
1117 Public Health And Health Services
Publication Status
Published
Coverage Spatial
England