Bayesian enrichment strategies for randomized discontinuation trials.

Abstract:

:We propose optimal choice of the design parameters for random discontinuation designs (RDD) using a Bayesian decision-theoretic approach. We consider applications of RDDs to oncology phase II studies evaluating activity of cytostatic agents. The design consists of two stages. The preliminary open-label stage treats all patients with the new agent and identifies a possibly sensitive subpopulation. The subsequent second stage randomizes, treats, follows, and compares outcomes among patients in the identified subgroup, with randomization to either the new or a control treatment. Several tuning parameters characterize the design: the number of patients in the trial, the duration of the preliminary stage, and the duration of follow-up after randomization. We define a probability model for tumor growth, specify a suitable utility function, and develop a computational procedure for selecting the optimal tuning parameters.

journal_name

Biometrics

journal_title

Biometrics

authors

Trippa L,Rosner GL,Müller P

doi

10.1111/j.1541-0420.2011.01623.x

subject

Has Abstract

pub_date

2012-03-01 00:00:00

pages

203-11

issue

1

eissn

0006-341X

issn

1541-0420

journal_volume

68

pub_type

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