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A bivariate Bayesian dose‐finding procedure applied to a seamless phase I/II trial in rheumatoid arthritis
Author(s) -
Thygesen Helene,
Dragalin Vladimir,
Whitehead Anne,
Whitehead John
Publication year - 2012
Publication title -
pharmaceutical statistics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.421
H-Index - 38
eISSN - 1539-1612
pISSN - 1539-1604
DOI - 10.1002/pst.1539
Subject(s) - rheumatoid arthritis , bivariate analysis , bayesian probability , placebo , medicine , clinical trial , statistics , mathematics , alternative medicine , pathology
We describe a dose escalation procedure for a combined phase I/II clinical trial. The procedure is based on a Bayesian model for the joint distribution of the occurrence of a dose limiting event and of some indicator of efficacy (both considered binary variables), making no assumptions other than monotonicity. Thus, the chances of each outcome are assumed to be non‐decreasing in dose level. We applied the procedure to the design of a placebo‐controlled, sequential trial in rheumatoid arthritis, in each stage of which patients were randomized between placebo and all dose levels that currently appeared safe and non‐futile. On the basis of data from a pilot study, we constructed five different scenarios for the dose–response relationships under which we simulated the trial and assessed the performance of the procedure. The new design appears to have satisfactory operating characteristics and can be adapted to the requirements of a range of trial situations. Copyright © 2012 John Wiley & Sons, Ltd.