Disability progression is a question of definition-A methodological reappraisal by example of primary progressive...

Different definitions of disability progression by Expanded Disability Status Scale (EDSS) may influence frequency and/or time to event.

In this multicenter cohort study, we included PPMS patients with follow-up ≥24 months and ≥3 available EDSS scores overall (≥1 per year). We applied 672 definitions of disability progression including different minimal EDSS increase, required confirmation and fixed/roving-baseline score.

We analyzed follow-up periods from 131 PPMS patients (median age at baseline 53.0 years [45.0 - 63.0], 51.9 % female, median follow-up 3.9 years [2.6 - 6.0], median baseline EDSS 4.0 [2.5 - 6.0]). The most sensitive definition of a progression event was an unconfirmed increase of ≥0.5 points with a roving baseline (81.8 % event rate). The least sensitive definition was an increase of ≥1.0 points with a fixed baseline, minimal distance to reference 48 weeks, and confirmed at ≥48 weeks (28.4 % event rate). Comparing roving vs. fixed baseline over all cutoffs and confirmation definitions, average time to progression was 227 days shorter applying the roving baseline (1405 days [550 - 2653] vs. 1632 days [760 - 2653]).

Different definitions of disability progression result in significantly differing rates of disability progression, which may influence study results and create confusion in clinical practice.