Comments on design and sequence of biomarker studies

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

2. Clinical use vs use as trial endpoint • Clinical use • 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 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. Gatsonis, Brown University

4. Aspects of marker performance Gatsonis, Brown University

5. Aspects of marker performance More evidence is needed for Phase II endpoint validation Gatsonis, Brown University

6. Aspects of marker performance Sequencing: Can all these be accomplished in one study, as is often required by reviewers of protocols? 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? Gatsonis, Brown University