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International Biometric Society
Adaptive designs and adaptive learning for biomarker-based clinical trials for targeted
therapies
J. Jack Lee, Ph.D.
Department of Biostatistics, University of Texas MD Anderson Cancer Center
Rapid advancements in genomics have changed the landscape of target
identification and drug development for targeted therapies. Targeted agents work
well when drugs are given to patients with the actionable targets. Targeted agents,
however, do not work for everyone and may not work at all. Hence, the goals for
developing target agents include (1) testing the treatment efficacy, (2) identifying
prognostic and predictive markers, and (3) providing better treatments to patients
enrolled in the trial. Several novel designs have been introduced to achieve these
objectives. For example, Bayesian adaptive designs can assign more patients to the
more effective treatments based on the available data at the time via the outcomeadaptive randomization. More frequent interim monitoring can drop the ineffective
treatments early for futility. New treatments can be added, and effective treatments
can graduate for further evaluation. The concepts of the basket design and the N-of-1
design have also been proposed to study the targeted agents based on patients’
genomic profiles across different disease sites. Information collected from such trials
can be put together to form a continuously updated knowledge database for adaptive
learning. Statistical methods such as the hierarchical model and Individual level
meta-analysis can be applied to model data collected in the knowledge database to
estimate the treatment effect, the marker effect, and their interactions. A platform of
a clinical trial infrastructure can be established to facilitate the conduct of such trials.
In the talk, pros and cons of various designs will be compared via simulation and
discussed. Examples and lessons learned from the recently completed BATTLE trial
and the on-going BATTLE-2 trial in non-small cell lung cancer will be given.
International Biometric Conference, Florence, ITALY, 6 – 11 July 2014