RV1 Vesikari 2011‐FIN

Methods	RCT Length of follow‐up: 2 months Adverse event data collection methods: passive. “Parents/guardians of infants were provided diary cards to record solicited general symptoms (loss of appetite, fussiness/irritability, fever, diarrhoea, vomiting, and cough/runny nose) during a 15‐day post‐vaccination follow‐up period. The intensity of each adverse event was assessed using a 4‐point scale where "0" refers to ‘absent’ and "3" refers to ‘severe’"
Participants	Number: 250 enrolled and randomized; ATP safety cohort: 240; ATP immunogenicity cohort: 237 Inclusion criteria: healthy infants aged 6 to 10 weeks with a birth weight > 2 kg. Exclusion criteria: any other investigational drug or vaccine 30 days prior to the administration of the first dose of the study vaccine; a history of allergy; rotavirus gastroenteritis; infants with acute illness at the time of enrolment could not receive the vaccine until the condition was resolved
Interventions	1. Liquid formulation of RIX4414*/(RV1), 1.5 mL (n=100) 2. Placebo corresponding to liquid vaccine formulation (n=25) 3. Lyophilized formulation RIX4414*/(RV1), 1 mL (n=100) 4. Placebo corresponding to lyophilized vaccine formulation (n=25) * vaccine containing at least 106 median CCID50 of live attenuated RIX4414 human rotavirus strain Schedule: 2 oral doses at month 0 and 1 (minimum time interval between doses: 14 days)
Outcomes	Clinical outcome measures (safety and efficacy) 1. Reactogenicity, occurrence of the symptom within the 15‐day solicited follow‐up period after each dose (collected from GSK report) 2. Serious adverse events, occurrence throughout study period 3. * Rotavirus diarrhoea, stool samples collected during diarrhoea episodes tested for rotavirus strains 4. * All‐cause diarrhoea, up to 1 month post‐dose 2 5. Dropouts: up to 2 months after dose 2 (collected from GSK report) 6. All‐cause death (collected from GSK report) 7. Adverse events resulting in discontinuation (collected from GSK report) Outcomes to measure immunogenicity 8. Seroconversion, antirotavirus IgA antibody concentration > 20 U/mL, 1 month after each dose (collected from GSK report) 9. Rotavirus vaccine virus shedding in stools, reported at peak (day 7 post‐dose 1) * Outcome reported as proportion (P) with 95% CI. Events (n) and totals (N) were estimated by using the value when 2 formulae for the standard error (SE) converged
Immunization status	Routine childhood vaccinations were allowed according to local practice, but at least 14 days apart from each dose of study vaccine
Location	5 centres in Finland WHO mortality stratum A
Notes	Study known as RIX GSK[048] 2007‐EU in previously published versions of this review Date: August to November 2005 Source of funding: GlaxoSmithKline Biologicals Study rationale: the immunogenicity, reactogenicity and safety of the RV1 liquid formulation were compared with lyophilized formulation and placebo
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Computer‐generated Quote: "A standard SAS® program was used for generating the randomization list and a block randomization was used in order to ensure that the balance between the treatment arms were maintained"
Allocation concealment (selection bias)	Low risk	Likely to be adequate: treatment masked to investigators Quote: "a unique randomization number identified the vials to be administered to the same subject" and "subjects were administered the vaccine dose with the lowest treatment number available at the study centre"
Blinding (performance bias and detection bias) All outcomes	Low risk	Participants and key personnel were blinded as far as technically possible Quote: "The study was double blind with respect to each of the vaccine formulation and their respective placebo; however, blinding between the two vaccine formulations was not technically possible because of the difference in appearance of the vaccines".
Incomplete outcome data (attrition bias) All outcomes	Low risk	Attrition balanced across study groups with reasons for dropout/exclusion reported
Selective reporting (reporting bias)	Low risk	All pre‐published outcomes reported
Other bias	Low risk	No apparent other bias