RV5 Iwata 2013‐JPN

Methods	RCT Length of follow‐up: 25 months Adverse event data collection methods: any death, vaccine‐related serious adverse events and intussusception were collected during the study period; parents/guardians asked to record adverse events on a standardized VRC during 14 days after each vaccination
Participants	Number: 762 Age range: 6 to 12 weeks Inclusion criteria: healthy Japanese Infants Exclusion criteria: history of known prior rotavirus gastroenteritis; infants who are concurrently participating in or are anticipated to participate in other studies of investigational products at any time during the study period
Interventions	1. Rotavirus vaccine, live, oral, pentavalent [RV5], 381 participants 2. Placebo (unspecified), 381 participants Schedule: 3 doses, 28 to 70 days apart, with 14 days of safety follow‐up after each vaccination, and follow‐up for acute gastroenteritis episodes until the end of the study
Outcomes	1. Efficacy against rotavirus gastroenteritis of any severity, at least 14 days following the 3rd vaccination 2. Efficacy against moderate to severe and severe rotavirus gastroenteritis, at least 14 days following the 3rd vaccination 3. Serious adverse events, including intussusception (data from correspondence with Merck; Merck 2012). 4. Reactogenicity (fever, vomiting, diarrhoea) 5. Dropouts before the end of the trial 6. Adverse events leading to discontinuation of the trial 7. Number of deaths (data from correspondence with Merck; Merck 2012)
Immunization status	No information about other vaccines given
Location	32 sites in Japan WHO mortality stratum A
Notes	Date: August 2008 to September 2009 Registration number: NCT00718237 Source of funding: Merck Sharp & Dohme Corp Rationale: "to evaluate whether V260 is effective and well tolerated in Japanese healthy infants"
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "Allocation number was assigned and the subject was randomized to the group receiving RV5 or the group receiving placebo in a 1:1 ratio according to the randomization code prepared by a computer at the US Merck Headquarters Office" (Merck 2012)
Allocation concealment (selection bias)	Low risk	Allocation numbers were generated and allocated centrally for participants (Merck 2012)
Blinding (performance bias and detection bias) All outcomes	Low risk	RV5 was visibly indistinguishable from placebo, investigators, study personnel (internal and external) and parents/guardians were blinded throughout trial (Merck 2012)
Incomplete outcome data (attrition bias) All outcomes	Low risk	Attrition/exclusions balanced across groups
Selective reporting (reporting bias)	Unclear risk	Insufficient information
Other bias	Low risk	No apparent other bias