RV5 Kim 2008‐KOR.

Methods	RCT Length of follow‐up: up to 42 days after last dose Adverse event data collection methods: diary cards (passive method)
Participants	Number: 178 enrolled; 171 evaluable Age range: 1 to 3 months (beginning); 3 to 6 months (end) Inclusion criteria: healthy infants; 6 to 12 weeks of age Exclusion criteria: history of congenital abdominal disorders, intussusception, or abdominal surgery; known or suspected impairment of immunological function; known hypersensitivity to any component of the rotavirus vaccine; prior receipt of any rotavirus vaccine; fever, with a rectal temperature ≥ 38.1 °C (≥ 100.5 °F) at the time of immunization; history of known prior rotavirus disease, chronic diarrhoea, or failure to thrive; clinical evidence of active gastrointestinal illness (infants with gastro‐oesophageal reflux disease were permitted to participate in the study as long as the gastro‐oesophageal reflux disease was well controlled with or without medication); receipt of intramuscular, oral, or intravenous corticosteroid treatment between the 2 weeks before first vaccination and 2 weeks after last vaccination; reside in a household with an immunocompromised person; prior receipt of a blood transfusion or blood products, including immunoglobulins; receipt of OPV during the course of the study or within 42 days before first dose of vaccine/placebo; and condition, which, in the opinion of the investigator, may have interfered with the evaluation of the study objectives
Interventions	RV5 1. WC3 (RV5): 6.9 to 8.6 x 107 PFU; 3 doses given 4 to 10 weeks apart; 115 participants (randomized) 2. Placebo: 3 doses given 4 to 10 weeks apart; 63 participants (randomized)
Outcomes	Clinical outcome measures (safety and efficacy) 1. Serious adverse events: no definition; measured up to 42 days 2. Reactogenicity: no definition; measured up to 14 days 3. Adverse events resulting in discontinuation Outcomes to measure immunogenicity 4. Seroconversion: sero‐response serum anti‐rotavirus immunoglobulin A (IgA) defined as an increase in antibody titre by a factor of ≥ 3 from baseline (data could not be extracted for review)
Immunization status	Infants excluded if they had or were to receive oral poliovirus vaccine at any time during the study or in the 42 days before the first dose; concomitant administration of other licensed vaccines and breast‐feeding was not restricted
Location	8 study centres in South Korea WHO mortality stratum B
Notes	Date: 2 August 2005 (first participant in) to 25 May 2006 (last dose given); last participant completed follow‐up on 5 July 2006 Source of funding: Merck & Co., Inc. Other: most of the outcome data are not provided in the reports
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Computer‐generated randomized 2:1 to receive hexavalent vaccine concomitantly with either RV5 (RotaTeq) or placebo (Merck 2012)
Allocation concealment (selection bias)	Low risk	Allocation numbers were generated for participants, investigators, adults, and parents/guardians of children were blinded throughout trial (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	High risk	Reason related to outcome
Selective reporting (reporting bias)	High risk	Key expected outcome not included
Other bias	Unclear risk	Information not provided