Clinical Trials of AD Delay of Onset: Enrichment by a Prognostic Genetic Biomarker


Modern medicine is shifting its focus to predictive and preventive healthcare utilization. To support this change, early intervention clinical trials that delay the onset of symptomatic disease must be conducted in a safe and cost-effective manner, and within a reasonable timeframe. Biomarkers in general, and pharmacogenetic determinants in particular, hold great promise for enabling the conduct of early intervention studies by allowing enrichment of the study population with high risk individuals while also minimizing participation of low risk subjects. In this chapter, we review one possible approach for the co-development of a therapeutic and companion prognostic. In the example cited, at the conclusion of the clinical trial, the biomarker will be evaluated for its utility in identifying individuals at risk of developing mild cognitive impairment (MCI) due to Alzheimer's disease (AD) in the next 5 years (i.e. prospective data will be generated to determine the biomarker's qualification as a prognostic). Simultaneously, the therapeutic will be evaluated for its efficacy in delaying the onset of MCI due to AD in high risk subjects with normal cognition at study entry. This clinical trial in planning is projected to launch internationally in 2013. The strategic and operational aspects of this development program are expected to pave the way to the application of similar approaches for other early intervention indications, particularly within the context of neurodegenerative diseases. © Springer Science+Business Media Dordrecht 2013.

Full Text

Duke Authors

Cited Authors

  • Grossman, I; Lutz, MW; Crenshaw, DG; Saunders, AM; Chiba-Falek, O; Gottschalk, WK; Roses, AD

Published Date

  • January 1, 2013

Volume / Issue

  • 3 /

Start / End Page

  • 141 - 160

International Standard Book Number 13 (ISBN-13)

  • 9789400759701

Digital Object Identifier (DOI)

  • 10.1007/978-94-007-5866-7_7

Citation Source

  • Scopus