AFFIRM 2006.
| Methods | RCT | |
| Participants | Age: 18 to 50 years; definite RRMS; median disease duration 5 years (range, 0 to 34 years); mean EDSS 2.3; prior use of DMT not reported | |
| Interventions | Natalizumab 300 mg by intravenous infusion once every 4 weeks for up to 116 weeks (n = 627) Placebo (unspecified) (n = 315) | |
| Outcomes | Relapse at 12 and 24 months. Disability worsening at 24 months | |
| Notes | Funding: Biogen Idec, Inc. and Elan Pharmaceutica | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | "Patients were randomly assigned to treatment that was stratified according to study site in blocks of three (two active, one placebo) with the use of a computer‐generated block randomization schedule" (Page 900) |
| Allocation concealment (selection bias) | Low risk | "A multidigit identification number, implemented by an interactive voice‐response system was used" (Page 900) |
| Blinding of participants and personnel (performance bias) All outcomes | Low risk | "All study personnel, patients, sponsor personnel involved in the conduct of the study, and the investigator advisory committee were unaware of treatment assignments throughout the study", and "Treating neurologists were responsible for all aspects of patient care, including the management of adverse events and the treatment of relapsing disease" (Pages 900‐1) |
| Blinding of outcome assessment (detection bias) All outcomes | Low risk | "Examining neurologists performed objective evaluation with use of the EDSS and neurologic examination during all study visits; they were not in contact with patients in any other capacity, so as to reduce the possibility of being unblinded by side effects or laboratory assessments", "Patients visited the clinic every 12 weeks for scoring on the EDSS", and "If a relapse was suspected, the patient was referred to the examining neurologist, who evaluated the patient within five days after the event" (Page 901) |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | Overall, 9.1% were lost‐to follow‐up (8.3% in natalizumab and 10.8% in placebo), without indication of the differences in reasons |
| Selective reporting (reporting bias) | Low risk | The published report included all pre‐specified primary benefit outcomes |
| Other bias | High risk | ‐ The study was sponsored by Biogen Idec and Elan Pharmaceuticals, "Data were analyzed by Biogen Idec and Elan Pharmaceuticals" (Page 909) and 4 co‐authors of the published paper were affiliated to the pharmaceutical company ‐ The primary benefit outcome measure for relapse (ARR) was strongly affected by differences among treatment groups both in the number of participants who discontinued the study and in time to discontinuation, which they did not report ‐ Relapse and disability worsening confirmed at 3 months outcomes were reported incompletely |