VAC Bhandari 2009‐IND.

Methods	RCT Length of follow‐up: 12 weeks Adverse event data collection methods: Caregivers reported any symptoms or illnesses to physician on‐call 24 hours; infants were visited at home daily the first 14 days after each administration
Participants	Number: 369 enrolled and randomized, 367 received at least one dose Age range: 8 to 9 weeks Inclusion criteria: healthy infants Exclusion criteria: family without access to a telephone, unavailable for follow‐up, weight‐for‐height z score of < 3 standard deviations, resided with an immunocompromised individual, born at a gestational age of < 37 weeks, major congenital abnormality, history of hospitalization for sepsis, pneumonia, or meningitis, diarrhoea in the previous 7 days, blood in stools any time after birth, need for daily medication, cardiovascular or neurological disease
Interventions	Rotavac 1. Rotavac vaccine (116E) (1 x 104 (low dose) or 1 x 105 FFU (high dose)), n = 185 2. Placebo, n = 184 Schedule: 3 doses given at 4‐week intervals at 8, 12, and 16 weeks of age
Outcomes	Clinical outcome measures (safety and efficacy) 1. All‐cause death 2. Intussusception (level 1 Brighton definition) 3. Serious adverse events 4. Reactogenicity (up to 14 days) Outcomes to measure immunogenicity 5. Immunogenicity: shedding 6. Immunogenicity: seroconversion (4‐fold increase in IgA antibody titer to rotavirus)
Immunization status	Infants received 3 doses of DTP; OPV; and Hep B at 6, 10, and 14 weeks of age
Location	1 site (New Delhi) in India WHO mortality stratum D
Notes	Date: November 2006 to February 2008 Registration number: NCT00439660; ISRCTN57452882 Source of funding: Department of Biotechnology, Government of India and PATH
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Infants were assigned to either the vaccine or placebo groups in a 1:1 ratio with use of a randomization sequence generated by a statistician not otherwise involved with the study (Stata software, version 8.0) with a fixed block length of 4
Allocation concealment (selection bias)	Low risk	Allocation concealment was achieved by using serially‐numbered sealed opaque envelopes. One set of envelopes was available with the independent vaccine‐dispensing team and another with the study data safety monitoring board
Blinding (performance bias and detection bias) All outcomes	Unclear risk	Study reported to be double‐blind but no further details were reported
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Intussusception data reported for all enrolled participants, immunogenicity and reactogenicity were not reported for all participants and the reason was not clear
Selective reporting (reporting bias)	Low risk	No indication of selective outcome reporting
Other bias	Low risk	No apparent other bias