Fall 2009 Meeting
Held on October 15,
2009 at the Marriot Renaissance Chicago North Shore Hotel in Northbrook, IL.
The Program will consist of two presentations:
Adaptive Design Considerations
for Evaluating Cardiovascular Risk among Patients with Type-2 Diabetes
Randomization Design - A Case Study and More
Yili Pritchett, PhD., & Shu Han, PhD., Abbott Laboratories
Adaptive Design Considerations for
Evaluating cardiovascular Risk among Patients with Type-2 Diabetes by Craig
Wilson, PhD., Takeda Pharmaceutical
Dr. Craig Wilson is a Principal Statistician at Takeda Global R&D in Lake
Forest , Illinois . Since receiving his PhD from Oklahoma State University
in 1998, Craig has served as study statistician and lead statistician on a
variety of drugs for treatment of T1DM and T2DM. During his time in
industry, Craig has had extensive discussions with the FDA regarding the
design and analysis of diabetes trials, including trial requirements for
satisfying the CV guidance.”
In December, 2008, the FDA released a final Guidance for Industry for
evaluating CV risk in subjects with T2DM. This guidance established criteria
for assessing the risk ratio of an investigational drug relative to control
in premarketing applications. In particular, if sufficient data are
available to rule out a risk ratio of 1.8, then an investigational drug may
be approved with a postmarketing commitment; if a risk ratio of 1.3 may also
be ruled out, then a postmarketing requirement to assess CV risk may not be
required. For sponsors with investigational drugs for treatment of T2DM
currently under development, one approach to satisfy this guidance is to
design a single stand-alone CV trial which may sequentially rule out risk
ratios of 1.8 and 1.3. This presentation will focus on design considerations
for such a trial including adaptive design issues. Discussion of the
pros/cons of Bayesian vs. group sequential design will be provided.
Randomization Design - A Case Study and More by Yili Pritchett, PhD. and Shu
Han, PhD., Abbott laboratories
Shu Han is currently a research statistician at Abbott
Laboratories, where he has played active role in the designs and implementations
of multiple clinical trials using Bayesian adaptive designs. Prior to joining
Abbott in 2006, Shu worked for Guidant/Boston Scientific Corporation, where
he collaborated with the FDA to design an adaptive seamless
exploratory-confirmatory clinical trial evaluating heart failure diagnostic
medical devices. Shu also worked for the Quantitative Science Division of M.D. Anderson Cancer Center as a Research Assistant to Dr. Donald A. Berry
from 2003 to 2005. Shu received his Ph.D. in statistics from a joint doctoral
program at M.D. Anderson Cancer Center and Rice University, after receiving
his Master's Degree in statistics from Columbia University. He is currently pursuing a
MBA degree at the University of Chicago.
Yili L. Pritchett is a Research
Fellow and a Director of Clinical Statistics in Global Pharmaceutical R&D at
Abbott Laboratories. She is responsible for statistical aspects of Phase II
– IV drug development in Neuroscience, Pain Care, and Renal Care therapeutic
areas. Before joining Abbott in April 2006, Dr. Pritchett was a Research
Advisor at Eli Lilly and Company where she provided statistical leadership
at various levels for the development and approval of several brands. Dr.
Pritchett obtained her Ph.D. in Statistics from the University of
Wisconsin–Madison in 1994. Dr.
Pritchett is an active member of PhRMA Adaptive Trial Design Working Group.
She has championed the use of adaptive design in Abbott, and led the efforts
of delivering a number of protocols with different types of adaptive design.
Dr. Pritchett authored or co-authored 46
peer-reviewed manuscripts or book chapters, and made over 100 presentations
at statistical or medical conferences.
In recent years, Bayesian adaptive
randomization design has been increasingly applied to clinical trails. In
this presentation, we will use a real case study to go through three major
mathematical components of the design: the modeling of dose-response
relationship, the algorithm of computing updated randomization ratio, and
the longitudinal model that predicts endpoint using partial observations. In
addition, the decision rules that allow the study to stop early due to
efficacy or futility will be explained, and the operating characteristics of
the design and the results of sensitivity analyses for the key parameters
will be illustrated. Simulation procedures via MCMC (Markov Chain Monte
Carlo) method will also be described. Lastly, other real clinical trial
cases where Bayesian adaptive designs were used to gain efficiency and
effectiveness in drug and medical device developments will be shared.