RV1 GSK[101555] 2008‐PHL

Methods	RCT Length of follow‐up: outcomes measured 1 month after last dose of vaccine/placebo Adverse event data collection methods: not reported
Participants	Number: 150 enrolled; 145 evaluable Age range: 6 to 12 weeks Inclusion criteria: healthy, full‐term infants aged 6 to 12 weeks; male or female infants between, and including, 6 and 12 weeks of age at the time of the first vaccination, free of obvious health problems, born after a normal gestation period (between 36 and 42 weeks) or with a birth weight > 2000 g Exclusion criteria: infants with previous confirmed occurrence of rotavirus gastroenteritis
Interventions	RV1 1. RIX4414 (RV1): 106.5; 100 participants* 1.1 Licensed formulation 1.2 Lyophilized formulation 2. Placebo: 50 participants* 2.1 Normal placebo 2.2 Lyophilized formulation Schedule: 2 doses starting at 6–12 weeks of age according to a 0, 2 month schedule *Data from the lyophilized formulation, which is not yet approved or marketed, are not reported in review
Outcomes	Clinical outcome measures (safety and efficacy) 1. Reactogenicity: for each type of solicited symptom, occurrence of the symptom within the 15‐day (day 0 to 14) solicited follow‐up period after each dose; occurrence of unsolicited adverse events within 31 (day 0 to 30) days after any doses of RV1 vaccine or placebo, according to MedDRA classification 2. Serious adverse events: occurrence throughout entire study period (up to 31 days after final dose of vaccine/placebo) 3. Dropouts: measured up to 31 days after final dose of vaccine/placebo 4. Rotavirus diarrhoea: presence of rotavirus in gastroenteritis stools collected until 1 month after dose 2 5. All‐cause death 6. Adverse events resulting in discontinuation Outcomes to measure immunogenicity 7. Vaccine viral shedding in stool (review includes data from combined time points) 8. Seroconversion: appearance of anti‐rotavirus IgA antibody concentration ≥ 20 U/mL in participants initially (i.e. before first dose of vaccine/placebo) negative for rotavirus (review includes data from 2 months after dose 1, 1 month after dose 2, and combined dose 1 and 2 at 1 month after dose 2)
Immunization status	Use of other vaccines not mentioned
Location	1 study centre in the Philippines WHO mortality stratum B
Notes	Date: 11 May 2004 to 13 September 2004 Source of funding: GlaxoSmithKline Biologicals Trial objective: "To assess the immunogenicity and safety of 2 different formulations of live attenuated HRV [human rotavirus] vaccine given as a two‐dose primary vaccination in healthy infants previously uninfected with HRV"
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: "The ATP cohort for immunogenicity included all vaccinated subjects: – who had received at least one dose of study vaccine/control according to their random assignment, – for whom the randomization code had not been broken"
Allocation concealment (selection bias)	Unclear risk	No details
Blinding (performance bias and detection bias) All outcomes	Unclear risk	No details; Quote: "Double‐blind with respect to each HRV [RV1] vaccine formulation and its respective placebo"
Incomplete outcome data (attrition bias) All outcomes	Low risk	5/100 participants withdrawn from the vaccine group
Selective reporting (reporting bias)	Low risk	All planned outcomes were reported
Other bias	Unclear risk	No details