Rodriguez 1997a.

Methods	Design: multicentre, parallel‐group RCT Setting: children's and university hospitals Duration: recruitment to discharge variable. Children were followed up in the next RSV season.
Participants	Location: USA Inclusion criteria High‐risk infants and young children including those with severe bronchopulmonary dysplasia, other severe lung disease, or congenital heart disease and infants born prematurely (< 32 weeks' gestation who were < 6 months old at the time of enrolment) Hospitalised for RSV bronchiolitis or pneumonia, or both, as defined by nasal specimens positive for RSV antigens by immunofluorescence or ELISA Aged up to 2 years Exclusion criteria Poorly controlled congestive heart failure before the RSV illness Renal failure Ventilator dependency before the RSV illness Life expectancy of less than 6 months from study onset Treatment with ribavirin before enrolment Previous adverse reaction to blood products Known serum immunoglobulin A deficiency or other immunodeficiency Enrolment in a concurrent RSV immunoglobulin prophylaxis study Patients with known cystic fibrosis, asthma, or reactive airway disease in the absence of bronchopulmonary dysplasia Patients presenting with apnoea without evidence of lower tract infection Baseline characteristics (N = 102 (of 107 children randomised)) Mean age (SE), months: treatment: 0.55 (0.07); comparator: 0.58 (0.06) Proportion male: treatment: 45%; comparator: 57% Health status/disease severity: children were described as high risk for severe RSV infection. High‐risk children included those with severe bronchopulmonary dysplasia, chronic lung disease, congenital heart disease, or prematurity. Mean (SE) respiratory score (score ranges from 0 to 5, with higher scores indicating more severe disease): treatment: 3.4 (0.2); comparator: 3.1 (0.1). Proportion with Lower Respiratory Tract Infection Score 5 (score ranges from 0 to 5, with 5 indicating respiratory failure): treatment: 31%; comparator: 18%
Interventions	Treatment (N = 54): 30 mL/kg RSVIG (1.5 mg/kg IVIG) given intravenously over 12 hours  Comparator (N = 54): 0.15 mg/kg of albumin given intravenously over 12 hours
Outcomes	Primary Duration of hospital stay (days) Secondary Duration of ICU stay (days) Duration of mechanical ventilation (days) Duration of oxygen therapy (days) Use of ribavirin Use of supplemental oxygen
Notes	Some members of the study group were employees of 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	Comment: the method used to generate the allocation sequence is unclear. There was insufficient information to permit judgement.
Allocation concealment (selection bias)	Low risk	Quote: "Each year of the study, MPHBL coded vials by one of six letters... Only MPHBL and the Data and Safety Monitoring Board member knew the contents of the vials until the study code was broken... Each centre received from MedImmune Inc a randomization schedule that ensured that each center enrolled nearly equal numbers of RSVIG and placebo patients by balancing randomisation in blocks of six. Patients who fit the inclusion criteria were assigned to the next lettered vial specified in the randomizations scheme for each centre." (p. 456) Comment: an adequate method was likely used to conceal the allocation sequence.
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Quote: "Bottles containing respiratory syncytial virus immunoglobulin or placebo were coded by the MPHBL so that contents were unknown to the investigators, sponsor, and study participants... A 0.5% solution of albumin bottled identically to the RSVIG was used as the placebo solution." (p. 456) Comment: it is likely that participants and care providers were blinded.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quote: "Bottles containing respiratory syncytial virus immunoglobulin or placebo were coded by the MPHBL so that contents were unknown to the investigators, sponsor, and study participants... A 0.5% solution of albumin bottled identically to the RSVIG was used as the placebo solution... Attending physicians not associated with the study were responsible for routine treatment... Furthermore, they determined when to administer supplemental oxygen, the level of oxygen therapy, or the need for mechanical ventilation. Likewise, the decision for hospital discharge was made by the attending physicians." (p. 456) Comment: it is likely that the personnel responsible for outcome data were blinded.
Incomplete outcome data (attrition bias) All outcomes	Low risk	Quote: "Fifty four patients were randomized to receive RSVIG, and 53 were randomized to receive placebo. Three children in the RSVIG group and 2 in the placebo group received less than 75% of the ordered dose and those were not evaluable for efficacy." (p. 457) Comment: the review authors judge that owing to the small number of participants not completing study treatments and excluded from the analysis, the similar numbers in each study group, and for reasons unlikely to be related to the outcomes, this is unlikely to have an important impact on the observed results.
Selective reporting (reporting bias)	Unclear risk	Comment: outcome data are reported for all outcomes specified in the methods section of the publication. However, without a trial protocol it is unclear whether other outcomes were measured but not reported based on the nature of the results.
Other bias	Unclear risk	Quote: "This work was supported by grant H5 MO1RR0069, General Clinical Research Centers program, from the National Institutes of Health (University of Colorado)." (p. 460) Comment: a number of members of the RSVIG Study Group were employees of MedImmune (manufacturer of RSVIG). This may lead to bias in favour of the intervention group.