Hello. My name is Gina Petroni and I am the director of the division of
Translational Research and Applied Statistics in the School of
Medicine's Department of Public Health Sciences at the University of Virginia.
My topic of presentation today is implementation
of adaptive methods in early phase clinical trials.
For this talk, I am assuming that there is initial understanding of the phases of
clinical research with early phase
referring to studies that assess safety and dose finding.
In addition, I am assuming there is familiarity with adaptive trial methodology.
Both the statistical and medical literature abounds with reviews,
justifications and recommendations on the use of
more novel designs to efficiently and accurately
address the objectives of finding
appropriate doses or dose combinations to merit further research.
These recommended designs are often referred to as adapted designs and
are based upon the premise that as safety and other information are acquired.
The whole of the information should be used to guide
those recommendations for future study participants.
Use of these model based designs remains infrequent.
This can be attributed to several causes
including a poor understanding from clinicians and reviewers
in how these designs actually work and how best
to evaluate the appropriateness of a proposed design.
These barriers are likely to be enhanced in the coming years as the recent paradigm of
drug development involves a shift to more complex dose finding problems.
So the purpose of this talk is not to advocate the use of
any particular body of adaptive designs but to provide recommendations on
the minimal information that should be included in a protocol to
aid in the understanding and approval of the protocol by
the various scientific and regulatory committees
that review them and to provide guidance on what
should be included in order to appropriately conduct the actual protocol specific design.