RV1 Zaman 2009‐BGD

Methods	RCT Length of follow‐up: 31 days after each vaccination (total of 14 weeks) Adverse event data collection methods: "active surveillance for reactogenicity and safety was conducted via daily home visits by study personnel for 8 days after each dose of vaccine or placebo dose and bi‐weekly home visits thereafter until one month after last dose" (active method); "During every episode, parents were asked to record in a daily diary card the number of looser than normal stools, axillary or rectal temperature, number of vomiting episodes, any rehydration or other medication administered, and any medical attention (defined as medical personnel contact, advice, or visit; emergency room contact or visit; or admission)" (passive method); serious adverse events were reviewed periodically by an independent committee
Participants	Number: 300 enrolled; 290 evaluable Age range: 1 to 3 months (beginning); 3 to 6 months (end) Inclusion criteria: healthy infants aged 6 to 7 weeks Exclusion criteria: acute disease at the time of enrolment; malnourished children; history of chronic administration of immunosuppressants since birth; received any vaccines or treatments prohibited by the protocol; or had any disorders or illnesses excluded by the protocol
Interventions	RV1 1. RIX4414 (RV1) 1.1. 1 x 106.5 dose + OPV; 100 participants (randomized) 1.2. 1 x 106.5 dose; 100 participants (randomized) 2. Placebo: 2.1. Placebo + OPV; 50 participants (randomized) 2.2. Placebo; 50 participants (randomized) Schedule: 2 doses given at a 6‐ to 12‐week interval
Outcomes	Clinical outcome measures (safety and efficacy) 1. Reactogenicity: for each type of solicited symptom, occurrence of the symptom within the 8‐day (Day 0 to 7) solicited follow‐up period after each dose; occurrence of unsolicited adverse events within 31 days (Day 0 to 30) after each dose, according to MedDRA classification; measured up to 31 days after vaccine/placebo 2. Serious adverse events: occurrence throughout entire study period (up to 105 days after vaccine/placebo) 3. Dropouts: measured up to 105 days after vaccine/placebo 4. Rotavirus diarrhoea: presence of rotavirus in gastroenteritis episode stools collected from dose 1 of vaccine/placebo up to 2 months after dose 2; measured up to 105 days after vaccine/placebo 5. All‐cause death 6. Adverse events resulting in discontinuation Outcomes to measure immunogenicity 7. Viral shedding: % participants with rotavirus antigen in stool samples collected at predetermined time points (ATP cohort for immunogenicity, stool analysis subset) (review includes data from combined time points) 8. Seroconversion: appearance of anti‐rotavirus immunoglobulin A antibody concentration ≥ 20 U/mL in participants who were negative for rotavirus before vaccination (review includes data from 1 month after dose 2)
Immunization status	All children in the study received the standard EPI vaccines starting at 6 weeks of age, including oral polio vaccine for 1 RV1 vaccine arm and 1 placebo arm
Location	Single site in urban Dhaka at Mirpur, Bangladesh WHO mortality stratum D
Notes	Date: June 2005 to January 2006 Source of funding: funded by GlaxoSmithKline Biologicals and the Rotavirus Vaccine Program (RVP) at the Program for Appropriate Technology in Health (PATH)
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	Likely to be adequate: treatment masked to investigators Quote: "A treatment number identified uniquely the vaccine doses to be administered to the same subject", and "subjects were administered the study vaccine dose (HRV vaccine or placebo) with the lowest number available at the study site"
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	Missing data imputed appropriately
Selective reporting (reporting bias)	Low risk	All planned outcomes were reported
Other bias	Unclear risk	No information