Adaptive Designs for Clinical Trials
Sunday morning, July, 8
Werner Brannath, Medical University of Vienna
Frank Bretz, Novartis Pharma AG
The aim of this short course is to give an introduction to the
principles and methodologies of adaptive designs for clinical trials.
Adaptive designs allow for mid-course design adaptations that are based
on un-blinded interim data as well as on all information from in- or
outside the trial without compromising the overall type I error rate.
Design adaptations could be adjustments of sample sizes and/or the
number of interim analyses that are based on interim estimates of the
variance, the treatment effect and safety parameters. Adaptive designs
are particularly useful in trials with multiple endpoints or with
several experimental treatments/doses. In this case one can also change
or select endpoints and drop or add treatments/doses at interim
analyses. This is of particular interest for drug development programs
to combine different phases (e.g. II and III) into a single trial.
Strategies for combining clinical phases may lead to substantial savings
in cost and time. Utilizing the adaptive design methodology and the
closed testing principle one can build adaptive designs that control the
multiple type I error rate. In order to control the multiple level one
need not prefix or fully anticipate the adaptations in advance. This
allows to react to unforeseen events and to implement complex decisions
that are based on convoluted internal and external information.
The course will provide an overview of methods from the published
literature of the last two decades including the most recent
developments. The course will discuss sample size adjustments and to a
large extend multiple hypotheses testing with adaptive designs.
Estimation following adaptive designs will also be a topic. Software
implementations and regulatory issues will be discussed as well. All
methods will be illustrated by examples or case studies.
- Introduction to adaptive designs: Motivation and methods
- Multiple hypotheses testing in adaptive designs: Methods and case
- Estimation in adaptive designs
- Software implementations
Werner Brannath, is Associate Professor in Biostatistics at the Medical
University of Vienna. He has received his PhD in mathematics in 1997 and
is working at the Department of Medical Statistics since August 1998. He
has written several papers on multiple testing and adaptive designs. One
of his research focuses is estimation in adaptive designs.
Frank Bretz, Ph.D., is Expert Statistical Methodologist, Novartis Pharma
AG. He received his PhD in biostatistics from the University of Hannover
in 1999 and continued working there from 2000 until 2004, when he joined
Novartis Pharma AG. He has been working on multiplicity issues arising
in clinical trials, dose finding trials and adaptive designs since 1997
and written several papers/chapters on these topics.
MCP-2009 - Japan
MCP-2005 - Shanghai
MCP-2002 - Bethesda
MCP-2000 - Berlin
MCP-1996 - Tel Aviv