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Seminar Announcement


Extension to Time to Event Data of the Outcome Adaptive Bayesian Dose Finding Procedure of Thall and Cook with Application to a Bone Marrow Transplant Trial

Marian Ewell

Vice President

The Emmes Corporation

Johnson Center 3rd Floor- Meeting Room D

4400 University Drive, Fairfax, VA 22030

Time: 11 am – 12 pm

Date: Friday, April 13, 2012 

Abstract

My talk will discuss research that I am conducting with Eric Leifer, a statistical colleague at the NHLBI.  We are studying two modifications to the outcome-adaptive, dose finding Bayesian procedure proposed by Thall and Cook (TC)(2004).  In the Phase I-II setting, the TC procedure assigns doses of an experimental drug to successive cohorts of subjects, using short-term efficacy and toxicity outcomes.  

 

The research is motivated by our application of the TC method to the BMT CTN protocol 0301, a multi-center trial in bone marrow transplantation for severe aplastic anemia. In this trial, enrollment is periodically suspended while awaiting 100-day post-transplant efficacy and toxicity outcomes.  If potential recruits cannot wait for a transplant, they must be turned-away and treated off-study.  Since severe aplastic anemia is a very rare disease (< 5 cases/million), this is very problematic.


As a result, we began studying how to modify the TC algorithm to incorporate incomplete subject follow-up data, with the goal of facilitating enrollment without sacrificing design performance. The first modification uses a bivariate time-to-event model for the efficacy and toxicity outcomes which allows for censoring.  The second modification is our adaptation of the look-ahead rule, introduced by Cook (2004), to bivariate binary and time-to-event outcomes. We examine the performance of both modifications in simulation studies.