RV5 Dhingra 2014‐IND.

Methods	RCT Length of follow‐up: 28 days after 3rd dose Adverse event data collection methods: Active and passive: "participants were observed for 30 min post vaccination for immediate adverse events at the study site. Subsequently, the subject’s parents/guardians were given a thermometer, a Symptom Diary (SD) covering Days 0–6 and a second SD covering Days 7–27 for safety follow up following each of the three doses. They were instructed to observe and record their child’s axillary temperature twice daily as well as any AEs up to 7 days after each dose in the first SD, and from day 7 to day 27 in the second SD. Parents/guardians were instructed to bring the study infants to the study clinic on Day 7 and Day 28 after each administration of the BRV‐TV vaccine/RotaTeq/Placebo as an outpatient and whenever any symptoms developed.The diary card contained list of solicited events and blank spaces to capture any unsolicited events"
Participants	Number: 100 enrolled; 100 evaluated Age range: 6 ‐ 8 weeks of age at time of enrolment Inclusion criteria: Healthy infants, of either sex, 6 ‐ 8 weeks of age at time of enrolment; born after a gestational period of 36 ‐ 42 weeks with birth weight > 2 kg Exclusion criteria: History of congenital abdominal disorders, intussusception, or abdominal surgery; infants exhibiting signs of severe malnutrition; known or suspected impairment of immunological function in participant or immediate family; developmental delay or neurological disorder; known hypersensitivity to any component of the rotavirus vaccine; fever; history of known rotavirus disease, chronic diarrhoea, or failure to thrive; any conditions which, in the opinion of the investigator, might interfere with the evaluation of the study objectives
Interventions	1. RV5 (2.0 mL) 2. BRV‐TV (2.0 mL), antigen concentration (105.0 FFU per serotype per dose) 3. BRV‐TV (2.0 mL), antigen concentration (105.8 FFU per serotype per dose) 4. BRV‐TV (2.0 mL), antigen concentration (106.4 FFU per serotype per dose) 5. Placebo (2.0 mL) Schedule: 3 doses of vaccines/comparator/placebo were administered at 6 – 8, 10 – 12 and 14 – 16 weeks of age
Outcomes	Clinical outcome measures (safety and efficacy) 1. All serious adverse events 2. Reactogenicity: fever, diarrhoea, vomiting 3. Dropouts before the end of the trial Outcomes to measure immunogenicity 4. Rotavirus vaccine shedding
Immunization status	Infants concomitantly received a combined Diphtheria, Tetanus, Whole‐cell pertussis, Hepatitis B and Haemophilus influenzae type b (DTPwHB‐Hib) pentavalent vaccine and Trivalent Oral Polio Vaccine
Location	2 sites, India WHO mortality stratum D
Notes	Alongside the infant cohort, the study also included an additional cohort of healthy adult volunteers Date: July 2012 ‐ not reported Source of funding: Shantha Biotechnics Limited Study rationale: study was carried out with the long‐term aim to produce a locally licensed vaccine which is equally safe and immunogenic as compared to available licensed vaccines
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Computer‐generated randomization.
Allocation concealment (selection bias)	Low risk	Likely to be adequate Quote: "Pre‐numbered or coded identical containers"
Blinding (performance bias and detection bias) All outcomes	High risk	Single‐blind, participant and outcome assessor blinded
Incomplete outcome data (attrition bias) All outcomes	Low risk	Outcome data presented for all 100 participants
Selective reporting (reporting bias)	Low risk	No indication of selective outcome reporting
Other bias	Low risk	No apparent other bias