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Seminar Announcement**
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*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.