1. Comments on design and sequence of biomarker studies
Constantine Gatsonis
Center for Statistical Sciences
Brown University
ACRIN Fall Meeting, 2008
ACRIN EISC 2008
Gatsonis, Brown University

2. Clinical use vs use as trial endpoint
Before Tx: stratification in order to decide on alternative treatments
During Tx:
early prediction of treatment response
basis for modifying therapy
After Tx:
monitoring for recurrence
ACRIN EISC 2008
Gatsonis, Brown University

3. Clinical use vs use as trial endpoint
Use as Phase II trial endpoint
Does image-based marker predict Phase III endpoints
at the patient level
at the trial level
Combining information from a group of studies is needed to “validate” marker for endpoint use.
ACRIN EISC 2008
Gatsonis, Brown University

4. Aspects of marker performance
Assay validation
Reliability/
Reproducibility
Diagnostic/
predictive accuracy
Effect on clinical outcomes
For clinical practice X x
For Phase II endpoint
ACRIN EISC 2008
Gatsonis, Brown University

5. Aspects of marker performance
Reliability/
Reproducibility
Diagnostic/
predictive accuracy
Effect on clinical outcomes
For clinical practice X x
For Phase II endpoint
More evidence is needed for Phase II endpoint
validation
ACRIN EISC 2008
Gatsonis, Brown University

6. Aspects of marker performance
Reliability/
Reproducibility
Diagnostic/
predictive accuracy
Effect on clinical outcomes
For clinical practice X x
For Phase II endpoint
Sequencing: Can all these be accomplished in
one study, as is often required by reviewers of
protocols?
ACRIN EISC 2008
Gatsonis, Brown University

7. Generalizable studies
Opportunity:
New imaging markers work a lot closer to the disease process and therapeutic intervention than morphologic imaging.
Challenge:
How granular should evaluation become?
Will it be necessary to evaluate marker in every disease/therapy combination?
ACRIN EISC 2008
Gatsonis, Brown University