RV1 Kawamura 2011‐JPN

Methods	RCT Length of follow‐up: up to the age of 2 years Adverse event data collection methods: not reported
Participants	Number: 765 Age range: 6 to 14 weeks Inclusion criteria: full‐term healthy infants aged 6 to 14 weeks at the time of the first dose Exclusion criteria: use of any other investigational or non‐registered product (drug or vaccine) within 30 days preceding the first dose of human rotavirus vaccine; history of use of experimental rotavirus vaccine; chronic administration of immunosuppressants or other immune‐modifying drugs since birth; concurrently participating in another clinical study; any clinically significant history of a serious medical condition; previous confirmed occurrence of rotavirus gastroenteritis
Interventions	1. RV1, 508 participants 2. Placebo, 257 participants Schedule: 2 doses according to a 0‐, 1‐month schedule
Outcomes	Clinical outcome measures (safety and efficacy) 1. Any rotavirus gastroenteritis leading to medical intervention and caused by the circulating wild‐type rotavirus strains, from 2 weeks after dose 2 up to 2 years of age, stool sample collected as soon as possible but preferably not later than 7 days after the start of the episode 2. Severe rotavirus gastroenteritis (≥ 11 on the Vesikari scale) leading to a medical intervention and caused by the circulating wild‐type rotavirus strains (a) of G1 type, (b) of non‐G1 types, from 2 weeks after dose 2 up to 2 years of age 3. Each type of solicited symptom (including: cough, diarrhoea, fever, irritability, loss of appetite and vomiting) during the 8‐day follow‐up period after each dose 4. Adverse events leading to discontinuation of the trial 5. Serious adverse events, including intussusception, up to 2 years of age 6. Fatal serious adverse events 7. Dropouts before the end of the trial Outcomes to measure immunogenicity 8. Seroconversion in terms of anti‐rotavirus IgA antibody, from 2 months after dose 2. Seroconversion was defined as the appearance of anti‐rotavirus immunoglobulin A antibody concentration over 20 units (U)/millilitre (mL) in infants initially (i.e. prior to the first dose of RV1) seronegative
Immunization status	Combined diphtheria and tetanus toxoids and acellular pertussis (DTPa) and Hepatitis B (HBV) vaccines were allowed to be co‐administered along with RV1 vaccine/placebo
Location	Japan WHO mortality stratum A
Notes	Date: June 2007 to November 2009 Source of funding: GlaxoSmithKline Registration number: NCT00480324
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
Blinding (performance bias and detection bias) All outcomes	Low risk	Parent/guardian and study personnel were not aware of the treatment administered
Incomplete outcome data (attrition bias) All outcomes	Low risk	Attrition/exclusions balanced between groups
Selective reporting (reporting bias)	Low risk	Protocol published a priori, all prepublished outcomes reported
Other bias	Low risk	No apparent other bias