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Blood Based Biomarkers: Where Are We Going?Howard Fillit, MDExecutive Director and Chief Science OfficerThe Alzheimer’s Drug Discovery Foundation
Intended Uses of Biomarkers• Research: understanding factors in pathogenesis, identifying and validating new drugtargets in preclinical and early clinical research• Diagnosis: the identification of the presence of Alzheimer’s disease (eg. PET amyloidimaging) for early detection and identification of patients for clinical trials • Screening: enabling intervention at an earlier and potentially more curable stage thanunder usual clinical diagnostic conditions (eg. cognitive function, blood based biomarkers)• Monitoring response during therapy, with potential for adjusting level of intervention (apharmacodynamic marker; eg. FDG-PET, CSF beta-amyloid/tau)• Risk prediction: identifying subpopulations who may respond to a treatment, and leadingto preventive interventions for those at sufficient risk (eg. apoE testing)2
Use of Biomarkers for Clinical Development inAlzheimer’s Disease• Efficacy response biomarker– may substitute for clinical response, making clinical trials more efficient, lesscostly– may be target specific– “Qualified biomarkers” used in FDA regulatory approval as supporting data forindication– Once validated by FDA, surrogate markers may be used in regulatory approval3
What is a Surrogate Marker?• A biomarker intended to substitute for a clinical endpoint inclinical trials and regulatory approval (eg. Cholesterol)• A surrogate endpoint is expected to predict clinical benefit (orharm, or lack of benefit) based onepidemiologic, therapeutic, pathophysiologic and otherscientific evidence4
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 forAlzheimer’s disease, or any neurodegenerative disease?7