Sorensen 2011.

Methods	A Multi‐centre, Double Blind, Randomised, Placebo Controlled, Parallel Group, Phase 4 Study. Random list generated was using a computer‐based blocking method. Allocation sequence was using central randomization by a third party (aCROnordic, Hørsholm, Denmark). Double blinded: all study personnel, participants and outcome assessors were blinded, the intervention drug and placebo were provided with identical appearance and delivered in sealed containers. Drop‐outs: Intervention group: 34 (22.5%) patients dropped out during the study, of them 12 patients dropped out before 12 months; Control group: 37 (23.7%) patients dropped out during the study, of them 21 patients dropped out before 12 months. Treatment duration: 12‐36 months, mean 20·6 months. Follow‐up period: 12‐36 months, mean 21.7 months. ITT analysis: yes.
Participants	Setting: 42 neurology department outpatient clinics in Denmark, Sweden, Norway, and Finland. 307 patients with clinically definite relapsing‐remitting MS according to revised McDonald or Poser criteria with an EDSS score of 5.5 or less and at least one documented relapse in the previous 12 months before enrolment. 151 in intervention group, F/M: 113/38, mean age 37.0 ± 8.6 years, disease duration 1.2 ± 2.2 years; 156 in control group, F/M: 108/48, mean age 36.1 ± 8.7 years, disease duration 1.3 ± 3.1 years. Characteristics of patients at baseline: similar
Interventions	Intervention group: IFN and simvastatin 80 mg/d for 1‐3 years Control group: IFN and placebo for 1‐3 years
Outcomes	1. Annual rate of documented relapses 2. The time to first documented relapse 3. Number of new or enlarging lesions on T2‐weighted MRI at 12 months 4. Proportion of patients without disease activity 5. Adverse events
Notes	The study was sponsored by Biogen Idec with a non‐conditional grant. Biogen Idec was not involved in the study design, data collection, data analysis and data interpretation. A documented relapse was defined as new or exacerbation of existing neurological symptoms or signs in the absence of fever, persisting for more than 48 h after a period of more than 30 days stable or improving. An undocumented relapse was defined as new symptoms or worsening of old symptoms over at least 48 h after 30 days or more of stability where the criteria did not fulfil a documented relapse. Progression was defined as an increase of 1 point or more on EDSS score for at least of 3 months.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Computer‐based blocking method
Allocation concealment (selection bias)	Low risk	Allocation sequence was using central randomization by a third party
Blinding (performance bias and detection bias) All outcomes	Low risk	Double blinded
Incomplete outcome data (attrition bias) All outcomes	High risk	The reasons of drop‐out and discontinuation were carefully recorded and balanced between groups, but the drop‐out rate exceed the assumed rate of 21%.
Selective reporting (reporting bias)	Low risk
Other bias	Low risk	Though the study was sponsored by the manufacturer Biogen Idec, conflict of interests may not exist.