VAC Bhandari 2006‐IND

Methods	Phase I RCT Length of follow‐up: 28 days Adverse event data collection methods: Caregivers reported any symptoms or illnesses on diary cards or to physician on‐call 24 hours; physicians and field investigators visited participants twice daily the first 14 days
Participants	Number: 90 enrolled, 90 randomized, 83 evaluable Age range: 8 weeks at enrollment and first dose Inclusion criteria: healthy, non‐malnourished infants Exclusion criteria: Evidence of renal, cardiovascular, liver or other reticuloendothelial, neurological, gastrointestinal, haematologic, rheumatologic or immunologic disease
Interventions	Rotavac 1. Rotavac vaccine (116E) (105 FFU), n = 30 2. Rotavirus vaccine candidate I321, n = 30 3. Placebo, n = 30 Schedule: 1 dose given at 8 weeks of age
Outcomes	Clinical outcome measures (safety and efficacy) 1. All‐cause death 2. Intussusception 3. Serious adverse events 4. Reactogenicity (up to 14 days) Outcomes to measure immunogenicity 5. Immunogrnicity: seroconversion (4‐fold rise in titre of IgA) 6. Immunogenicity: shedding
Immunization status	Infants were vaccinated with DPT, Hep B and OPV separately from rotavirus vaccine
Location	1 site (Delhi) in India WHO mortality stratum D
Notes	Date: January to May 2005 Registration number: NCT00280111; ISRCTN57452882 Source of funding: Bharat Biotech International Ltd. Notes: study arm administered vaccine candidate I321 was excluded from data analysis
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "For randomisation, a sequence of codes was generated using Stata, version 8 (Statacorp, College Station, TX, USA) by a statistician not otherwise involved with the trial."
Allocation concealment (selection bias)	Low risk	Quote: "Two copies of the randomisation code were prepared; one was sent to the Division of Microbiology and Infectious Diseases (DMID) at the NIH under sealed cover, and the second was given to a physician, not otherwise involved in the study, for reconstituting the vaccine/placebo at the time of enrolment."
Blinding (performance bias and detection bias) All outcomes	Low risk	Quote: "Double‐blind" Quote: "The placebo was constituted by adding a crystal of potassium permanganate to sodium bicarbonate buffer and appeared identical to the vaccines but did not contain the virus."
Incomplete outcome data (attrition bias) All outcomes	Low risk	Low attrition, reasons for loss to follow‐up were reported and evenly spread across groups
Selective reporting (reporting bias)	Low risk	No indication of selective reporting, all outcomes in the trial register reported
Other bias	Low risk	No apparent other bias