RV1 Dennehy 2005‐NA

Methods	RCT Length of follow‐up: 10 to 12 months Adverse event data collection methods: "For the 15 days after each dose of vaccine, the parent or guardian maintained a daily record that included fever, irritability/fussiness, diarrhoea, vomiting, loss of appetite and cough/runny nose. In addition, the parent or guardian was asked to record any gastroenteritis episode occurring in the period from the first dose until 2 months after the second dose of vaccine." (passive method); "Subjects were also monitored for any serious adverse events occurring throughout participation in the study (10–12 months in total) and for unsolicited adverse events occurring within 43 days after each dose of vaccine or placebo" (active method)
Participants	Number: 529 enrolled; 479 evaluable Age range: 1 to 3 months (beginning) Inclusion criteria: healthy infants aged 5 to 15 weeks at the time of the first dose. Vaccine administration delayed if acute illness present (fever > 38 °C/gastroenteritis/antibiotics within 7 days before scheduled vaccination) Exclusion criteria: premature labour (< 36 weeks); chronic condition; (chronic gastrointestinal disease, immunosuppressive diseases); household contact with immunosuppressed individuals/pregnant women
Interventions	RV1 1. RIX4414 (RV1) 1.1. 105.2; 212 participants 1.2. 106.4; 209 participants 2. Placebo: 108 participants Schedule: 2 doses given 7 weeks apart
Outcomes	Clinical outcome measures (safety and efficacy) 1. Reactogenicity: fever, irritability/fussiness, diarrhoea, vomiting, loss of appetite and cough/runny nose; measured during 15 days post‐vaccination 2. Serious adverse events 3. Adverse events resulting in discontinuation Outcomes to measure immunogenicity 4. Viral shedding: viral shedding in any stool specimen collected between first dose and 2 months after second vaccine dose (review includes after dose 2 data) 5. Seroconversion: anti‐rotavirus IgA ELISA ≥ 20 Units/mL in participants negative for rotavirus antibody before the first dose of vaccine (review includes data from 2 months after dose 2)
Immunization status	Vaccine or placebo given concomitantly with diphtheria‐tetanus‐acellular pertussis, inactivated poliovirus, H. influenzae type b, and Streptococcus pneumoniae conjugate vaccines for participants in USA or with a diphtheria‐tetanus‐acellular pertussis/inactivated poliovirus/H. influenza type b combination vaccine for participants in Canada "Routine hepatitis B vaccinations were administered according to local practice"
Location	41 centres in USA and Canada WHO mortality stratum A
Notes	Date: 13 December 2000 to 2 August 2002 Source of funding: GlaxoSmithKline Biologicals
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Computer‐generated, using a SAS programme
Allocation concealment (selection bias)	Low risk	Central allocation Quote: "double blind randomized unbalanced allocation scheme (2:2:1 ratio)"
Blinding (performance bias and detection bias) All outcomes	Low risk	Participants and key personnel; Quote: "Study personnel and families were blinded to group assignment until study completion"
Incomplete outcome data (attrition bias) All outcomes	Low risk	Missing data balanced across groups Quote: "Fifty‐nine subjects, who were proportionately distributed among vaccine groups, did not complete the entire 10‐ to 12‐month study"
Selective reporting (reporting bias)	Unclear risk	No details
Other bias	Unclear risk	No details