title: Addressing potential prior-data conflict when using informative priors in proof-of-concept studies.
abstract: Bayesian methods are increasingly used in proof-of-concept studies. An important benefit of these methods is the potential to use informative priors, thereby reducing sample size. This is particularly relevant for treatment arms where there is a substantial amount of historical information such as placebo and active comparators. One issue with using an informative prior is the possibility of a mismatch between the informative prior and the observed data, referred to as prior-data conflict. We focus on two methods for dealing with this: a testing approach and a mixture prior approach. The testing approach assesses prior-data conflict by comparing the observed data to the prior predictive distribution and resorting to a non-informative prior if prior-data conflict is declared. The mixture prior approach uses a prior with a precise and diffuse component. We assess these approaches for the normal case via simulation and show they have some attractive features as compared with the standard one-component informative prior. For example, when the discrepancy between the prior and the data is sufficiently marked, and intuitively, one feels less certain about the results, both the testing and mixture approaches typically yield wider posterior-credible intervals than when there is no discrepancy. In contrast, when there is no discrepancy, the results of these approaches are typically similar to the standard approach. Whilst for any specific study, the operating characteristics of any selected approach should be assessed and agreed at the design stage; we believe these two approaches are each worthy of consideration.
authors.affiliation: UCB BioPharma SPRL, Global Exploratory Development, Chemin du Foriest, Belgium, B-1420 Braine-l'Alleud, (currently at Arlenda S.A., 93 Chaussée Verte, 4470 Saint-Georges sur Meuse, Belgium).
authors.forename: Timothy
authors.initials: T
authors.lastname: Mutsvari
authors.affiliation: UCB BioPharma SPRL, Global Exploratory Development, Chemin du Foriest, B-1420 Braine-l'Alleud, Belgium, (currently at Clinical Pharmacokinetics/Pharmacometrics, Sanofi-Aventis Deutschland GmbH, Frankfurt am Main, Germany).
authors.forename: Dominique
authors.initials: D
authors.lastname: Tytgat
authors.affiliation: UCB Pharma, Global Exploratory Development, 208 Bath Road, Slough, Berkshire SL1 3WE, UK.
authors.forename: Rosalind
authors.initials: R
authors.lastname: Walley
mesh_terms: D001499:Bayes Theorem; D017322:Clinical Trials, Phase II as Topic / Q000706:statistics & numerical data*; D006801:Humans; D015233:Models, Statistical; D013223:Statistics as Topic / Q000592:standards
keywords: Bayesian analysis; informative prior; mixture prior; prior-data conflict; proof-of-concept; robust prior