Arnon 2006

Methods	Randomized, placebo‐controlled, participant‐, study investigator‐, and outcome assessor‐blinded trial
Participants	129 participants with initial clinical findings consistent with infant botulism, which was later confirmed with Clostridium botulinum toxin or organisms isolated in stool or enema, who had been admitted to hospital for less than 3 days by the time of study inclusion. Mean age of the intervention group was 131 days, 47% of whom were male, while the mean age of the placebo group was 105 days, 32% of whom were male (the remainder were female).
Interventions	Intervention: human‐derived botulism immune globulin intravenous 50 mg/kg, single dose (n = 65) Placebo: "Identical‐appearing" intravenous immune globulin (Gammagard or Gammagard S/D) that did not neutralize botulinum toxin in the mouse bioassay (n = 64)
Outcomes	Length of hospital stay required (measured in weeks, defined as the time required until the fulfillment of certain criteria for discharge including no further need for inpatient care for infant botulism or its complications, no need for mechanical ventilation or supplemental oxygenation for at least 3 days, no worsening of paralysis in the previous 3 days and a demonstrated improvement in motor and bulbar function, 3 days of intake by tube feeding of 25% or less of maintenance volume and calories) Length of intensive care unit stay (weeks) Duration of mechanical ventilation (weeks) Duration of tube or intravenous feeding (weeks) Number of adverse events per participant Total hospital charges per participant (USD)
Conflicts of interest	No major conflicts of interest
Funding	A co‐operative agreement between the US Food and Drug Administration Office of Orphan Products Development and the Calfiornia Department of Public Health
Notes	Length of follow‐up limited to duration of hospitalization. Intervention group was older (mean 131 versus 105 days old), heavier (mean weight 6.7 kg versus 5.9 kg), and more likely to be male (47% versus 32%), demonstrating that randomized treatment allocation was not entirely successful. The review authors were unable to obtain individual patient data and therefore had to reconstruct standard deviations using the 95% confidence interval provided in the original article. Due to the rounding of values in the original article, this led to small discrepancies between our calculated 95% confidence interval and those reported in the original article. Conducted from 1992 to 1997 in the USA
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Trialists used a printed random‐number table to generate a number that was associated with 1 of 8 letter codes stamped on the drug vials through the use of a master sequential list.
Allocation concealment (selection bias)	Low risk	The study statistician performed allocation using a printed random‐number table to assign a letter code‐associated drug vial to each participant. The study statistician kept the master sequential list, and it was unavailable to the study investigators.
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Participants and study investigators appeared to have been blinded to allocation status, although it would have been preferable if there had been an attempt to measure the success of this blinding in survey participants and study investigators to see whether they were able to successfully guess allocation status.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Although the published manuscript was not clear, we contacted the authors who confirmed that the outcome assessors were blinded to allocation status.
Incomplete outcome data (attrition bias) All outcomes	High risk	All participants enrolled into the trial were included in the primary analysis (length of hospital stay), with the exception of those participants found after randomization not to have laboratory‐confirmed infant botulism (6 treatment participants, 1 control participant). On the other hand, the authors excluded participants never admitted to the intensive care unit or never mechanically ventilated from the "Length of intensive care unit stay" and "Duration of mechanical ventilation" analyses, compromising randomized treatment allocation and allowing for possible between‐treatment group imbalances and uncontrolled confounding. The safety analysis included all enrolled participants.
Selective reporting (reporting bias)	Low risk	The report fully describes the results for all outcomes.
Other bias	Low risk	No apparent other bias