Ramilo 2014.

Methods	Design: multicentre, parallel‐group, 3‐arm RCT Setting: hospitals, not further described Duration: 1 year from randomisation to final follow‐up
Participants	Location: "Northern and Southern Hemispheres", "5 countries". Trial registry indicates study sites in USA, Panama, Chile, New Zealand, and Australia. Inclusion criteria Previously healthy infants of ≥ 36 weeks gestational age Aged ≤ 12 months Hospitalised for LRTI with a documented positive RSV test Exclusion criteria Receiving antiviral treatment for the current RSV infection Use of steroids within 30 days of randomisation Medically significant underlying illness Intubation for ventilatory support, previous supplemental oxygen use, or mechanical ventilation at randomisation Receipt of palivizumab or other immunoglobulin products during the 2 months before randomisation Baseline characteristics (N = 118) Median age (range), months: treatment: 2.0 (0.4 to 11.2) for the 30 mg/kg arm and 2.2 (0.3 to 11.3) for the 100 mg/kg arm; comparator: 2.7 (0.5 to 10.3) Proportion male: treatment: 51% for the 30 mg/kg arm and 51% for the 100 mg/kg arm; comparator: 73% Health status/disease severity: children were described as "previously healthy" (p. 703). Median (range) Respiratory Distress Assessment Instrument (RDAI) score (17‐point scale, with higher score indicating more severe wheezing and retractions): treatment: 6 (0 to 17) for the 30 mg/kg arm and 6 (0 to 13) for the 100 mg/kg arm; comparator: 4 (0 to 15)
Interventions	Treatment (N = 39): single IV dose of motavizumab 30 mg/kg Treatment (N = 39): single IV dose of motavizumab 100 mg/kg Comparator (N = 40): placebo (not further described)
Outcomes	RSV viral load in nasal wash specimens by reverse transcriptase polymerase chain reaction collected on days 0 to 6 (if still hospitalised), 7, 30, 90, 180 Duration of hospitalisation (days) Supplemental oxygen use (number of study participants) and duration of use (days) Mechanical ventilation use (number of study participants) and duration of use (days) Admission to ICU (number of study participants) and duration of stay (days) Adverse events Wheezing episodes during 12‐month follow‐up
Notes	This study was sponsored by the manufacturer of the immunoglobulin used in the study.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: "Eligible subjects were randomized to 1:1:1..." (p. 704) Comment: the method used to generate the allocation sequence is unclear. There is insufficient information to permit judgement.
Allocation concealment (selection bias)	Low risk	Quote: "Eligible subjects were randomized to 1:1:1 using an interactive voice response system to receive... The interactive voice response system was also used for assignment of patient identification number and assignment of blinded study drug kits." (p. 704) Comment: an adequate method was used to conceal the allocation sequence.
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Quote: "...assignment of blinded study drug kits ...Subjects parents/guardians, clinical site staff and protocol‐associated personnel were blinded to group assignment." (p. 704) Comment: it is likely that participants and care providers were blinded, although the appearance of the interventions is not described.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quote: "Subjects parents/guardians, clinical site staff and protocol‐associated personnel were blinded to group assignment... At a central laboratory, personnel who were blinded to treatment assignment tested nasal specimens..." (p. 704) Comment: personnel responsible for the virologic and clinical outcome data were blinded.
Incomplete outcome data (attrition bias) All outcomes	Low risk	Quote: "A total of 118 subjects were randomized... and 113 subjects received study drug. One hundred and seven subjects completed through study day 90 and 98 subjects completed through study day 360. Similar rates of non‐completion were observed among subjects treated with motavizumab or placebo." (p. 704) Comment: 91% (107/118) of randomised participants remained in the study at day 90, with a similar number of non‐completers in the study groups. Clinical outcome data are provided for 112 of 113 participants who received the study drug (1 participant was found to be negative for RSV at study day 0). Of the 112 participants with clinical outcome data, duration of hospitalisation data are available for 111 (1 participant in the motavizumab 30 mg/kg group withdrew consent). The review authors judge that the reasonably small number of participants randomised but not included in the analysis and the similar numbers lost to follow‐up in the study groups is unlikely to have an important impact on the observed results.
Selective reporting (reporting bias)	Low risk	Comment: outcome data were fully reported for all outcomes specified in ClinicalTrials.gov registry entry NCT00421304.
Other bias	High risk	Quote: "This study was sponsored by MedImmune." (p. 703) Comment: the study was sponsored by MedImmune (the manufacturer of motavizumab), and a number of the study investigators received funding from or were employees of MedImmune. This may lead to bias in favour of the intervention group.