Table 1.

 List of sensitivity analyses undertaken with rationale

Problem to be addressed	Sensitivity analysis
Patients switching treatment might have particularly poor outcomes so excluding them might bias results	Calculate on “intent to treat” basis, retaining all such patients in analysis
Patients converting from RRMS to SPMS but remaining on DMTs might have particularly aggressive disease, so excluding them might bias results	Retain patients in analysis after developing SPMS and still taking DMTs; calculate “expected” benefit on assumption that DMTs modify natural rate of disease progression by same factor as shown for RRMS in randomised controlled trials*
Results might be distorted by small number of outliers	Exclude patients with 1% most extreme movement (up or down) in EDSS score
Bias because of lack of year three data for some patients needed to confirm apparent progression at year two	Limit analysis to subset of patients with data for year three
Bias because of lack of year three data for some patients needed to confirm apparent progression at year two	Use all available data to estimate proportion of apparent progressions subsequently confirmed and apply this to patients with apparent progression at year two but no year three data*
Possible bias because of missing year two data (see below)	Perform “best case/worst case” analysis to impute missing year two values—for “best case” assume no further disease progression after year one, for “worst case” extrapolate from progression between baseline and year one
Possible bias because of retrospective adjustment of baseline data for some patients	Leave baseline EDSS values unadjusted while continuing to apply “smoothing” algorithm to subsequent data points

RRMS=relapsing-remitting multiple sclerosis; SPMS=secondary progressive multiple sclerosis; DMTs=disease modifying treatments; EDSS=expanded disability status scale.

*Pre-specified analysis