Table 2

Sensitivity analyses (EDSS basis)

VariantPatients (n)Mean yearsAbsolute treatment effect (EDSS)Relative treatment effect (EDSS)
Follow-upOn treatmentMarkov modelMLMMarkov modelMLM
Primary analysis48628.77.00.12 (0.07, 0.17)0.61 (0.55, 0.66)93% (90%, 96%)72% (69%, 74%)
RRMS-only subgroup42178.97.30.25 (0.20, 0.31)0.68 (0.62, 0.74)86% (83%, 89%)69% (67%, 72%)
Supplementary/sensitivity analyses (including patients with SPMS at baseline except where noted)
Excluding EDSS scores recorded after a patient has switched to a non-scheme DMT*
Primary analysis cohort47998.06.40.13 (0.08, 0.19)0.59 (0.53, 0.64)91% (88%, 95%)70% (68%, 73%)
RRMS-only subgroup†41578.16.70.26 (0.21, 0.32)0.66 (0.60, 0.72)84% (81%, 88%)68% (65%, 71%)
Excluding EDSS scores recorded after a patient has switched to any other DMT*
Primary analysis cohort44757.05.70.16 (0.11, 0.22)0.57 (0.52, 0.62)88% (84%, 92%)68% (65%, 70%)
RRMS-only subgroup38717.05.90.29 (0.23, 0.35)0.64 (0.59, 0.70)80% (76%, 84%)65% (62%, 68%)
Imputation—Markov model, using imputed values derived from the MLM
‘on treatment’ assumption48629.97.70.12 (0.07, 0.17)NA93% (91%, 96%)NA
‘off treatment’ assumption48629.97.00.10 (0.04, 0.15)NA95% (92%, 98%)NA
Imputation—multilevel model
‘on treatment’ assumption48629.99.9NA0.67 (0.62, 0.72)NA72% (70%, 74%)
‘off treatment’ assumption
Single imputation48629.99.9NA0.65 (0.59, 0.70)NA73% (70%, 75%)
Multiple imputation48629.99.9NA0.64 (0.59, 0.70)NA73% (71%, 75%)
Single imputation +0.5 EDSS points for each imputed value48629.99.9NA0.48 (0.43, 0.53)NA80% (78%, 82%)
Supplement RSS data with imputed values derived from out-of-window year 10 scores‡48628.97.00.12 (0.07, 0.18)93% (90%, 96%)
Use transition matrices from BCMS data set supplemented by imputing additional data for patients with sparse follow-up‡
Including patients with SPMS at baseline48628.77.00.28 (0.23, 0.34)84% (81%, 87%)
Excluding patients with SPMS at baseline42178.97.30.43 (0.37, 0.49)78% (75%, 81%)
Alternative Markov model with time-varying natural history transition matrices48628.77.00.48 (0.42, 0.53)NA76% (74%, 79%)NA
Year 1 baseline (see online supplementary appendix 8)43607.96.20.07 (0.02, 0.12)0.43 (0.38, 0.48)95% (92%, 99%)77% (74%, 79%)
  • *Patients switching before year 1 are also excluded from the analysis.

  • †This was the primary analysis for the interim year 6 analysis.

  • ‡These variants were only carried out for the Markov model.

  • DMT, disease-modifying treatment; EDSS, Expanded Disability Status Scale; MLM, multilevel model; NA, not applicable; RRMS, relapsing remitting multiplesclerosis; RSS, risk sharing scheme; SPMS, secondary progressive multiple sclerosis;BCMS, British Columbia Multiple Sclerosis.