1. Blood Based Biomarkers: Where Are We Going?
Howard Fillit, MD
Executive Director and Chief Science Officer
The Alzheimer’s Drug Discovery Foundation

2. Intended Uses of Biomarkers
• Research: understanding factors in pathogenesis, identifying and validating new drug
targets in preclinical and early clinical research
• Diagnosis: the identification of the presence of Alzheimer’s disease (eg. PET amyloid
imaging) for early detection and identification of patients for clinical trials
• Screening: enabling intervention at an earlier and potentially more curable stage than
under usual clinical diagnostic conditions (eg. cognitive function, blood based biomarkers)
• Monitoring response during therapy, with potential for adjusting level of intervention (a
pharmacodynamic marker; eg. FDG-PET, CSF beta-amyloid/tau)
• Risk prediction: identifying subpopulations who may respond to a treatment, and leading
to preventive interventions for those at sufficient risk (eg. apoE testing)
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3. Use of Biomarkers for Clinical Development in
Alzheimer’s Disease
• Efficacy response biomarker
– may substitute for clinical response, making clinical trials more efficient, less
costly
– may be target specific
– “Qualified biomarkers” used in FDA regulatory approval as supporting data for
indication
– Once validated by FDA, surrogate markers may be used in regulatory approval
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4. What is a Surrogate Marker?
• A biomarker intended to substitute for a clinical endpoint in
clinical trials and regulatory approval (eg. Cholesterol)
• A surrogate endpoint is expected to predict clinical benefit (or
harm, or lack of benefit) based on
epidemiologic, therapeutic, pathophysiologic and other
scientific evidence
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http://www.fda.gov/downloads/Drugs/NewsEvents/UCM300734.pdf

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http://www.fda.gov/downloads/Drugs/NewsEvents/UCM300734.pdf

7. Some Issues in Biomarker Development
• Standardization and replication of assays
• Clinical study design
– Lack of a priori hypothesis testing
– Inadequate power, small sample sizes
– Failure to account for co-morbidities
– Exploratory studies often not confirmed in validation samples
– No effective therapies to validate use
– Publication bias
• Can a blood-based biomarker be developed for
Alzheimer’s disease, or any neurodegenerative disease?
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