RV1 Zaman 2017‐BGD.

Methods	Cluster‐RCT, open‐label, cluster‐randomized (by village), parallel‐group field trial with an observed‐only control group Length of follow‐up: 2 years Adverse event data collection methods: (not reported if active of passive)"Serious adverse events among infants vaccinated with HRV were assessed by the principal investigator or trained study physicians and followed to resolution"
Participants	Number: 12,318 enrolled; 11,004 evaluable Age range: 6 to 20 weeks Inclusion criteria: 6 to 20 weeks of age, having primary residence at the time of DTP1 receipt in a village selected for introduction of HRV, and having a parent or guardian provide written informed consent Exclusion criteria: history of intussusception, hypersensitivity to the active substance or any component in the vaccine, uncorrected congenital malformation of the gastrointestinal tract, or known or suspected immunodeficiency. Infants with an acute febrile illness were temporarily excluded from HRV vaccination only if that illness was severe enough to warrant postponement of other EPI vaccinations. Infants with current diarrhoea or vomiting or both were not excluded unless the illness met the aforementioned temporary exclusion criterion
Interventions	1. RV1; 1‐ml dose of HRV (Rotarix; GSK Biologicals, Rixensart, Belgium) (n=71 villages with 6527 age‐eligible infants) 2. Non‐placebo controlled (observed only controls) (n=71 villages with 5791 age‐eligible infants) Schedule: at 6 and 10 weeks of age
Outcomes	Clinical outcome measures (safety and efficacy) 1. Severe rotavirus diarrhoea 2. Serious adverse events
Immunization status	HRV was scheduled to be given along with other standard infant vaccines including OPV at the DTP1 and DTP2 immunization visits, recommended in Bangladesh to occur at 6 and 10 weeks of age.
Location	142 study sites (cluster‐randomized villages), Bangladesh WHO mortality stratum D
Notes	Date: September 2008 to March 2011 Source of funding: GAVI and PATH Study rationale: The primary objective of the trial was to estimate the overall effectiveness of an HRV vaccination programme in reducing the risk of presenting with acute rotavirus diarrhoea to a treatment facility among all children who had been age‐eligible for vaccination with HRV during the vaccination programme
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Villages were randomized in a 1:1 ratio for introduction of HRV or not. Prior to study initiation, PATH computer‐generated the allocation sequences using block randomization with block sizes of 12
Allocation concealment (selection bias)	Unclear risk	The generated allocation sequences were securely transferred to the principal investigator, who distributed the sequences to the field supervisors who oversaw HRV vaccinations
Blinding (performance bias and detection bias) All outcomes	High risk	The study was conducted open‐label without masking, and field staff conducting the vaccinations were unblinded. Medical staff collecting clinical data on diarrhoeal presentations and laboratory personnel conducting assays on stools were not informed of previous HRV receipt of participants
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Outcome data available for 11,004/12,318 enrolled participants
Selective reporting (reporting bias)	High risk	Online registration of trial ( NCT00737503) indicates all‐cause diarrhoea as an outcome but results were not reported for this outcome in the study report
Other bias	Unclear risk	Cluster‐randomized trial.