Background: Baseline
Expanded Disability Status Scale (EDSS) is usually based on a single
measurement. Here we evaluated whether using
a baseline EDSS derived from two pre-treatment
measurements improves the detection of progression events and the
ability to
demonstrate a therapeutic effect in delaying MS
disability progression.
Methods: Real data
from OLYMPUS, a phase II/III randomized, placebo-controlled trial of
rituximab in patients with primary progressive
multiple sclerosis (PPMS), as well as simulated
data were analyzed. Several definitions of baseline EDSS were used to
capture
sustained disability progression (SDP) events.
Variations in the EDSS were estimated by linear mixed-effect models.
Results: Selecting the
higher of two baseline EDSS scores lowered the number of SDP events in
both treatment groups, so decreasing
sensitivity, and reduced the number of false SDP
events, so increasing specificity. Conversely, selecting the lower of
two
baseline scores increased sensitivity but
decreased specificity. Increased power (~7% based on the simulation
study) was observed
when the average of screening and Week 0 EDSS
scores was used for baseline.
Conclusion: Baseline
EDSS derived from two pre-treatment EDSS measurements may enhance the
ability of detecting a therapeutic effect
in slowing disability progression in PPMS. This
strategy could be implemented in future clinical trials of patients with
MS.
Doing two assessments of EDSS as a baseline may make the baseline more accurates such that it may be more easy to detect change in progressive MS
