RV1 Anh 2011‐PHL

Methods	RCT Length of follow‐up: 1 month after last dose Adverse event data collection methods: not reported
Participants	Number: 375 enrolled; ATP safety cohort: 345; ATP immunogenicity cohort: 292 Inclusion criteria: healthy infants aged 5 – 10 weeks at the time of the first study vaccination dose with a birth weight of > 2 kg Exclusion criteria: use of any investigational drug or vaccine other than the study vaccine or confirmed immunosuppression/immunodeficient conditions or allergy to RIX4414 vaccine/placebo components
Interventions	1. 2 doses of RIX4414* plus 1 dose of placebo according to a PL‐V‐V schedule 2. 2 doses of RIX4414* plus 1 dose of placebo according to a V‐PL‐V schedule 3. 3 placebo doses * Human rotavirus (RV1) liquid vaccine, oral suspension (GSK Biologicals, Belgium), containing at least 106.0 median Cell Culture Infective Dose 50 percent (CCID50) of live attenuated RIX4414 human rotavirus strain (G1P[8]) Schedule: 3 doses according to a 0‐, 1‐, and 2‐month schedule
Outcomes	Clinical outcome measures (safety and efficacy) 1. Reactogenicity, including fever, diarrhoea and vomiting, 8 days after each dose (collected from GSK report) 2. Adverse events leading to discontinuation 3. Serious adverse events 4. Fatal serious adverse events 5. Dropouts 6. * Rotavirus diarrhoea, rotavirus antigen isolated from any of the stool samples collected from children with diarrhoea episodes, up to 1 month after last dose 7. * All‐cause diarrhoea, up to 1 month after last dose Outcomes to measure immunogenicity 8. Anti‐rotavirus IgA antibody seroconversion, ≥ 20 U/mL * Outcome reported as proportion (P) with 95% CI. Events (n) and totals (N) were estimated by using the values when 2 formulae for the standard error (SE) converged
Immunization status	Commercially‐available diphtheria, tetanus, whole‐cell pertussis (DTPw), hepatitis B (HBV) and oral poliovirus (OPV) vaccines were administered concomitantly with the study vaccine/placebo as part of the routine Expanded Programme of Immunization (EPI) in the Philippines
Location	Philippines (single centre) WHO mortality stratum B
Notes	Study known as RIX GSK[063] 2008‐AS in previously published versions of this review Date: March to September 2007 Source of funding: GlaxoSmithKline Biologicals Study rationale: "This study will provide data on the immune response and safety of GSK Biologicals' HRV [human rotavirus] liquid vaccine when given along with the routine infant immunizations in Philippines." "The study also[...]explored the potential effect of scheduling of the HRV [human rotavirus] vaccine doses with respect to the existing routine vaccination schedules"
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Computer generated Quote: "Block randomization scheme (2:2:1 ratio) with standard SAS program was used"
Allocation concealment (selection bias)	Low risk	Central allocation Quote: "Based on the block size, the vaccine doses were distributed to each of the study centers"
Blinding (performance bias and detection bias) All outcomes	Low risk	Participants and key personnel were blinded Quote: "The study was double‐blind with respect to the RIX4414 oral suspension (liquid formulation), placebo and scheduling of doses. The parents/guardians of infants, investigators and study personnel were unaware of the study vaccine/ placebo administered" Quote: "The placebo was identical to the vaccine in composition"
Incomplete outcome data (attrition bias) All outcomes	Low risk	Attrition balanced across groups with reasons for dropout/exclusion reported
Selective reporting (reporting bias)	Low risk	All prepublished outcomes included
Other bias	Low risk	No apparent other bias