Standardized Statistical Framework for Comparison of Biomarkers

• Activity Number: 300
• Type: Contributed
• Date/Time: Tuesday, July 31, 2012 : 8:30 AM to 10:20 AM
• Sponsor: Biopharmaceutical Section
• Author(s): Danielle J Harvey*+ and Clifford Jack Jr and Norbert Schuff and Michael Weiner and Laurel Beckett
• Companies: University of California at Davis and Mayo Clinic and University of California at San Francisco and University of California at San Francisco and University of California at Davis
• Keywords: biomarker comparison ; precision ; clinical validity

Abstract

Alzheimer's disease (AD) is widespread in the elderly population and clinical trials are ongoing, focused on elderly individuals with AD or at apparent risk for AD, to identify drugs that will help with this destructive disease. Well-chosen biomarkers have the potential to increase the efficiency of clinical trials and drug discovery and should show good precision in detecting change over time as well as clinical validity. We propose measures that operationalize these criteria and describe a general family of statistical techniques that can be used for inference-based comparisons of biomarker performance. The methods are illustrated using volumetric and cortical thickness measures quantified from magnetic resonance imaging obtained over time as part of the Alzheimer's Disease Neuroimaging Initiative, on individuals with AD and with mild cognitive impairment, many at risk for progressing to AD. Strengths of the approach include the ability to simultaneously compare performance across a large number of biomarkers collected on individuals, even if they are measured on different scales. Limitations include the need to have complete data on all biomarkers across individuals.