RV1 Madhi 2010‐AF.

Methods	RCT Length of follow‐up: outcomes measured 2 weeks after last dose to 1 year of age, and at 2 years Adverse event data collection methods: active surveillance for all gastroenteritis episodes was conducted by members of the study staff through weekly visits to parents or guardians to collect diary cards and through the collection of data from health clinics that served the study populations
Participants	Number: 4939 enrolled; 4417 evaluable Age range: 1 to 6 months Inclusion criteria: healthy infants aged 6 to 10 weeks for the group receiving 3 doses and 10 to 14 weeks for the group receiving 2 doses of RV1 Exclusion criteria: children HIV‐positive that were immunosuppressed at < 6 weeks before vaccination
Interventions	RV1 1. RIX4414 (RV1): dose same as commercial; 3298 participants 1.1 2 doses 1.2 3 doses 2. Placebo: 1641 participants 2.1 Normal placebo Schedule: 2 to 3 doses given 1 month apart
Outcomes	Clinical outcome measures (safety and efficacy) 1. All‐cause diarrhoea 2. Rotavirus diarrhoea: stool samples were tested for rotavirus with the use of an enzyme‐linked immunosorbent assay (ELISA) (Rotaclone, Meridian Bioscience) 3. Severe rotavirus diarrhoea: the severity of each episode of gastroenteritis was evaluated with the use of the Vesikari scale 13 (on which scores range from 1 to 20, with higher scores indicating greater severity) and was categorized as severe if the score was 11 or more * 4. Severe all‐cause diarrhoea: the severity of each episode of gastroenteritis was evaluated with the use of the Vesikari scale 13 (on which scores range from 1 to 20, with higher scores indicating greater severity) and was categorized as severe if the score was 11 or more 5. All‐cause mortality: all serious adverse events including deaths were recorded for the period between the date the first dose of vaccine or placebo was administered and the date the child reached 1 year of age 6. Serious adverse events: all serious adverse events including deaths were recorded for the period between the date the first dose of vaccine or placebo was administered and the date the child reached 1 year of age Outcomes to measure immunogenicity 7. Immunogenicity: ELISA ‐ 1 month after the last dose to determine the serum concentrations of antirotavirus IgA antibody
Immunization status	Vaccines that are administered routinely according to the guidelines of the Expanded Programme on Immunization (EPI) were concomitantly administered with the vaccine or placebo, including oral polio vaccine
Location	South Africa and Malawi WHO mortality stratum E
Notes	This trial was conducted in Malawi and South Africa, with data reported separately by country available under RV1 Madhi 2010‐MWI and RV1 Madhi 2010‐ZAF Date: October 2005 to February 2007 (South Africa); October 2006 to July 2007 (Malawi) Source of funding: PATH Rotavirus Vaccine Programme and GlaxoSmithKline
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	A randomization list was generated at GSK Biologicals, Rixensart, using a standard SAS® (Statistical Analysis System) programme and this was used to number the vaccines
Allocation concealment (selection bias)	Low risk	The vaccine doses were distributed to each study centre while respecting the randomizations block size
Blinding (performance bias and detection bias) All outcomes	Low risk	The site investigator was unaware of the group assignments of the children
Incomplete outcome data (attrition bias) All outcomes	Low risk	Missing data balanced across groups
Selective reporting (reporting bias)	Low risk	All expected outcomes reported
Other bias	Low risk	No apparent other bias