ONMRG 1999.

Methods	Method of randomization: “Randomly assigned by the envelope method” Number randomized: 102 Exclusions after randomization (total and per group): 32 dismissed after start of study due to different reasons including misdiagnosis and lost data. 2 patients excluded before treatment, 2 more during treatment due to waiver of consent by the patients. (Final: 66 - 33 Treatment, 33 Control groups). Exclusions per group not explicitly stated Losses to follow up: No loss to follow up Method of allocation concealment: Serially numbered in sealed opaque envelopes Participant masking: Yes Provider masking: No (attending physician was informed of the intervention) Outcome assessor masking: Yes Intention to treat analysis: No
Participants	Country and period of study: 22 centers in Japan (March 1991 to December 1996) Age: 14 to 58 (Mean 36.3 years) Sex: Overall, 69% were female
Interventions	Treatment: Intravenous methylprednisolone (1 g/d) for 3 days followed by oral corticosteroid for 7 to 10 days. Intravenous administration was carried out over 45 to 60 minutes once a day in the morning Control: Intravenous mecobalamin (500 ug/d) for 3 days, followed by oral mecobalamin for at least 7 days. Intravenous administration was carried out over 45 to 60 minutes once a day in the morning
Outcomes	Visual acuity (Measured using Landolt rings at 5 m after full refractive correction. Results expressed as decimal activity) Visual field (Humphrey 30-2 for central 30 degrees of visual field and Goldmann perimetry for peripheral field if HFA unsuitable) Contrast sensitivity (Visual Contrast Test System at a testing distance of 1 m)
Notes	Data provided by Masato Wakakura about allocation concealment and outcomes Follow up at 1, 3, 4, 12 weeks and 12 months Four patients had definite or probable multiple sclerosis
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Method of sequence generation was not reported
Allocation concealment (selection bias)	Unclear risk	“treatment was randomly assigned by the envelope method” - details of envelopes (e. g. sequentially numbered, opaque, sealed, etc.) were not reported
Masking (performance bias and detection bias)	Low risk	“In this study, it was the policy to inform neither the patient nor examiner which treatment was being used, although it was known by the attending physician”
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	“Data for 70 patients were analyzed in the baseline study. Four patients were subsequently eliminated just before the start of treatment (n=2) or during treatment (n=2), because they had decided not to give their consent” “HFA mean deviation could be determined for only 46 cases…Color vision could be examined in 52 eyes in the first 12 weeks of the study…Contrast sensitivity data were obtained for 37 eyes. CFF was measured for 51 eyes” “No patient was required to drop out of the study”
Selective reporting (reporting bias)	Low risk	Results for all outcomes were reported
Other bias	Unclear risk	Some data were presented by eyes rather than by the unit of randomization, which was the individual