RV1 Kim 2012‐KOR

Methods	RCT Length of follow‐up: 1 month post‐dose 2 Adverse event data collection methods: Passive: Adverse events were recorded during the 8‐day and 31‐day follow‐up period after each dose of RIX4414/placebo, respectively. SAEs were recorded during the entire study period
Participants	Number: 684 enrolled; 642 evaluable Age range: 6 to 12 weeks Inclusion criteria: Infants who the investigator believes that their parents/guardians can and will comply with the requirements of the protocol should be enrolled in the study: male or female between, and including, 6 to 12 weeks of age at the time of the first dose of the vaccination, healthy infants as established by medical history and clinical examination, born after a normal gestation period of between 37 and 41 weeks + 6 days inclusive, available vaccination history from vaccination diary cards or medical charts Exclusion criteria: Use of any investigational or non‐registered product (drug or vaccine) other than the study vaccine(s) within 30 days preceding the dose of study vaccine, or planned use during the study period, chronic administration (defined as more than 14 days) of immunosuppressants or other immune‐modifying drugs since birth, planned administration/ administration of a vaccine not foreseen by the study protocol within 30 days of the first dose of vaccine, with the exception of the routine infant vaccines, concurrently participating in another clinical study, confirmed or suspected immunosuppressive or immunodeficient condition, clinically significant history of chronic gastrointestinal disease including any uncorrected congenital malformation of the gastrointestinal tract or other serious medical condition as determined by the investigator, history of allergic disease or reactions likely to be exacerbated by any component of the vaccine, acute disease at the time of enrolment, administration of immunoglobulins or any blood products, or both, since birth or planned administration during the study period, gastroenteritis (GE) within 7 days preceding the study vaccine administration, previous confirmed occurrence of RV GE, previous vaccination with rotavirus vaccine or planned use during the study period
Interventions	1. RV1 2. Placebo Schedule: 2 oral doses according to a 0‐, 1‐, or 2‐month schedule
Outcomes	Clinical outcome measures (safety and efficacy) 1. All‐cause deaths 2. All serious adverse events 3. Serious adverse events: intussusception 4. Rotavirus diarrhoea: of any severity (up to 2 months follow‐up) 5. All‐cause diarrhoea: of any severity (up to 2 months follow‐up) 6. Reactogenicity: vomiting, diarrhoea, fever 7. Adverse events requiring discontinuation 8. Dropouts from the trial Outcomes to measure immunogenicity 9. Seroconversion
Immunization status	Routine childhood vaccines as recommended by the local vaccination schedule were allowed to be administered concomitantly with RIX4414/placebo. These vaccines included the combined diphtheria‐tetanus‐acellular pertussis vaccine, Haemophilus influenzae type b vaccine, inactivated poliovirus vaccine and pneumococcal vaccine. The infants had received the BCG vaccine and 2 doses of hepatitis B vaccine prior to study enrolment
Location	19 sites, Republic of Korea WHO mortality stratum B
Notes	Date: August 2009 to July 2010 Source of funding: GlaxoSmithKline Study rationale: To evaluate Immunogenicity, Reactogenicity and Safety of Rotarix™ Vaccine in Korean Infants
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "All infants receiving RIX4414 or placebo were allocated into their respective groups using an internet based randomization tool SBIR (Internet based randomization system) according to 3:1 ratio" Quote: "A standard SAS® program generated a randomization list used to number the vaccines. A randomized (3:1) blocking scheme maintained the balance between the two treatments where a unique treatment number identified the study vaccine to be administered to the infants."
Allocation concealment (selection bias)	Low risk	The person in charge of the vaccination accessed the randomization system on Internet. Upon providing a participant number and the age (6 ‐ 12 weeks) for the infant, the randomization system used the minimization algorithm to determine the treatment number to be used for the participant. The actual treatment number used for first vaccination of the participant was recorded by the investigator in the eCRF (Randomisation/Treatment Allocation Section)
Blinding (performance bias and detection bias) All outcomes	Low risk	Quote: "Each dose of RIX4414 or placebo was administered in a blinded manner where the parents/guardians and the physicians were unaware of the vaccine administered"
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	462/684 completed the study, reasons for attrition provided
Selective reporting (reporting bias)	Low risk	No indication of selective reporting bias
Other bias	Low risk	No apparent other bias