title: Developing a Bayesian adaptive design for a phase I clinical trial: a case study for a novel HIV treatment.
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 However, the effort was worthwhile as the originally proposed rule-based design has been replaced by a more efficient Bayesian adaptive design.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. Copyright © 2016 John Wiley & Sons, Ltd.
authors.affiliation: Department of Health Services Research and Policy, London School of Hygiene and Tropical Medicine, 15-17 Tavistock Place, London, WC1H 9SH, U.K.
authors.forename: Alexina J
authors.initials: AJ
authors.lastname: Mason
authors.affiliation: Imperial Clinical Trials Unit, Imperial College London, 68 Wood Lane, London W12 7RH, U.K.
authors.forename: Juan
authors.initials: J
authors.lastname: Gonzalez-Maffe
authors.affiliation: Section of Infectious Diseases, Department of Medicine, Imperial College London, London, W2 1PG, U.K.
authors.forename: Killian
authors.initials: K
authors.lastname: Quinn
authors.affiliation: Section of Infectious Diseases, Department of Medicine, Imperial College London, London, W2 1PG, U.K.
authors.forename: Nicki
authors.initials: N
authors.lastname: Doyle
authors.affiliation: Section of Infectious Diseases, Department of Medicine, Imperial College London, London, W2 1PG, U.K.
authors.forename: Ken
authors.initials: K
authors.lastname: Legg
authors.affiliation: Section of Infectious Diseases, Department of Medicine, Imperial College London, London, W2 1PG, U.K.
authors.forename: Peter
authors.initials: P
authors.lastname: Norsworthy
authors.affiliation: HIV i-Base.
authors.forename: Roy
authors.initials: R
authors.lastname: Trevelion
authors.affiliation: Section of Infectious Diseases, Department of Medicine, Imperial College London, London, W2 1PG, U.K.
authors.forename: Alan
authors.initials: A
authors.lastname: Winston
authors.affiliation: Imperial Clinical Trials Unit, Imperial College London, 68 Wood Lane, London W12 7RH, U.K.
authors.forename: Deborah
authors.identifier: 0000-0003-3146-7466
authors.initials: D
authors.lastname: Ashby
mesh_terms: D001499:Bayes Theorem; D017321:Clinical Trials, Phase I as Topic / Q000379:methods*; D023381:Endpoint Determination; D015700:HIV Envelope Protein gp41; D023581:HIV Fusion Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D010446:Peptide Fragments
chemical_list: D015700:HIV Envelope Protein gp41; D023581:HIV Fusion Inhibitors; D010446:Peptide Fragments; C407149:peptide C34
keywords: Bayesian adaptive designs; HIV clinical trials; continual reassessment method; dose-finding studies; fusion inhibitor; phase I