Using Ordered Values of Longitudinal Changes in Regional Knee Cartilage Thickness as an Efficacy Biomarker in Osteoarthritis

• Activity Number: 157
• Type: Topic Contributed
• Date/Time: Monday, August 4, 2014 : 10:30 AM to 12:20 PM
• Sponsor: Biopharmaceutical Section
• Author(s): Robert Buck*+
• Companies: StatAnswers Consulting LLC
• Keywords: ordered values ; biomarkers ; MRI ; osteoarthritis

Abstract

Knee cartilage loss varies spatially, as well as temporally, across osteoarthritis patients. Knee cartilage can be subdivided into disjoint regions; let X1, ., Xr, represent the (possibly normalized) cartilage change in r regions in each subject. The ordered values, X(1), ., X(r), represent change independent of spatial location and provide an opportunity to compare different locations across subjects with the same internal relative ranking of cartilage change. Ordered values can then be used to compare different cohorts, notably treatment and control, for differences in disease progression. Empirical evidence from osteoarthritis studies indicate that X(1) may be more sensitive than f(X1, ., Xr) for common aggregating functions f in detecting differences in cartilage loss between cohorts. The improved sensitivity depends on the spatial variability and magnitude of cartilage change relative to measurement error. This presentation will look at some of the benefits and challenges when using ordered values to compare disease progression in different cohorts.