2015/02/10_Micha Mandel (The Hebrew University of Jerusalem)

Estimating Time to Disease Progression Using Panel Data, with Application to Multiple Sclerosis

2015/02/10 – 13:00 h | Micha Mandel, Department of Statistics – The Hebrew University of Jerusalem

Abstract

The expanded disability status scale (EDSS) is an ordinal score that measures progression in multiple sclerosis (MS). Progression is defined as reaching an EDSS of a certain level (absolute progression) or increasing in the EDSS by one point (relative progression). Survival methods for time to progression do not exploit the EDSS level at the end of follow-up. Instead, we suggest a Markov transition model applicable for repeated categorical or ordinal data. This approach enables derivation of covariate-specific survival curves, obtained after estimation of the regression coefficients and manipulations of the resulting transition matrix. Large-sample theory and resampling methods are employed to derive pointwise confidence intervals, which perform well in simulation. Methods for generating survival curves for absolute and relative progression are described explicitly. We compare the transition model approach to survival analysis methods, and discuss the differences in the interpretations of the estimated parameters. We apply the models to data obtained from two phase 3 clinical trials and find that both yield positive effects for a new oral treatment for multiple sclerosis, and provide similar estimates for the probability of disability progression over time. Parts of this talk are joint with Rebecca Betensky, Francois Mercier, Susan Gauthier, Howard Weiner, Charles Guttmann, Ben Eckert, and Peter Chin.

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