RV1 Rivera 2011‐DOM

Methods	RCT Length of follow‐up: 17 weeks Adverse events data collection methods: not reported
Participants	Number: 200 Age range: 6 to 14 weeks of age at the time of the first study vaccination Inclusion criteria: healthy infants with a live twin living in the same household who is also enrolled in this study, born after a gestation period of over 32 weeks Exclusion criteria: use of any investigational or non‐registered product other than the study vaccine(s); any confirmed or suspected immunosuppressive or immunodeficient condition; any clinically significant history of chronic gastrointestinal disease; history of allergic disease; acute disease at time of enrolment; gastroenteritis within 7 days preceding the first study vaccine administration; documented HIV‐positive infant
Interventions	1. RV1 (RIX 4414) Vaccine, 100 participants 2. Placebo, 100 participants Schedule: both vaccine and placebo 2 doses at Day 0 (Visit 1) and Week 7 (Visit 2) Notes: 1 complimentary dose of RV1 was administered to all infants enrolled in this study (both study groups) who are aged less than 6 months at Visit 3 (Week 13) as a benefit to the placebo group for participation in the study
Outcomes	Clinical outcome measures (safety and efficacy) 1. Gastroenteritis, up to week 17 2. Rotavirus gastroenteritis, up to week 13. Rotavirus gastroenteritis episodes were defined as gastroenteritis episodes for which the stool sample temporally closest to the onset day of the gastroenteritis episode was positive for rotavirus by ELISA 3. Serious adverse events, including fatal serious adverse events and intussusception, up to week 17 4. Dropouts from the study Outcomes to measure immunogenicity 5. Anti‐rotavirus IgA antibody seroconversion and concentration in each group, at visit 3
Immunization status	All infants received 3 doses of combined diphtheria, tetanus, acellular pertussis, hepatitis B, inactivated poliovirus and H. influenzae vaccine
Location	Dominican Republic WHO mortality stratum B
Notes	Study known as RV1 NCT00396630 2009‐LA in previously published versions of this review. Date: January 2007 to February 2008 Source of funding: GlaxoSmithKline Registration number: NCT00396630 Aim: "to explore horizontal transmission of the HRV [human rotavirus] vaccine strain within a family from the twin vaccinated with Rotarix to the twin receiving placebo"
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "A randomization list was generated at GlaxoSmithKline (GSK) Biologicals, Rixensart, using a standard SAS® program. A randomization blocking scheme (1:1 ratio, block size = 2) was used to ensure balance between the treatment arms; a treatment number uniquely identified the vaccine doses to be administered to the same infant"
Allocation concealment (selection bias)	Low risk	Quote: "No investigator or any person involved in the clinical trial (including laboratory personnel, statisticians and data management) was aware of the treatment groups during the course of the study"
Blinding (performance bias and detection bias) All outcomes	Low risk	Quote: "The study was double‐blinded and the parents/guardians of infants, investigator and the study personnel were unaware of the study vaccine administered"
Incomplete outcome data (attrition bias) All outcomes	Low risk	Attrition/exclusions balanced between groups
Selective reporting (reporting bias)	Low risk	Trial report does not provide enough details
Other bias	Low risk	No apparent other bias