RV5 Lawrence 2012‐CHN

Methods	RCT Length of follow‐up: 2 weeks after last dose Adverse event data collection methods: not reported
Participants	Number: Infant cohort: 48 enrolled and randomized, child cohort: 48 enrolled and randomized Inclusion criteria: healthy infants aged 6 to 12 weeks, and healthy children aged 2 to 6 years, there was also a cohort of adults (not reported in this review) Exclusion criteria: receiving other live vaccines 14 days before or after study vaccine; prior administration of any rotavirus vaccine; elevated temperature, with axillary temperature ≥ 37.1 °C 24 hours before study vaccine; prior or active gastrointestinal illnesses; immunodeficiency
Interventions	1. 2.0 mL RV5 (V260) administered orally. The vaccine consists of an oral solution of 5 live human‐bovine reassortant rotaviruses (24 infants, 24 children) 2. 2.0 mL matching placebo to RV5 administered orally (24 infants, 24 children) Schedule: infant cohort: 3 doses of RV5/placebo at 3 separate visits scheduled 28 to 70 days apart. The third dose was administered by 32 weeks of age; child cohort: one dose
Outcomes	Clinical outcome measures 1. Serious adverse events, up to 14 days post‐vaccination, including intussusception (data from correspondence with Merck; Merck 2012).  2. Adverse events requiring discontinuation 3. Dropouts from the trial 4. Number of deaths (data from correspondence with Merck; Merck 2012). 5. Reactogenicity Outcomes to measure immunogenicity 6. Vaccine virus shedding in stools, day 3 to day 7 following each of the 3 doses of RV5/placebo
Immunization status	Other live vaccines 14 days before or after study vaccine were not allowed
Location	China WHO mortality stratum B
Notes	Date: September 2009 to March 2010 Source of funding: Merck Sharp & Dohme Corp Study rationale: "This study will assess the safety and tolerability of RV5 (V260) in the healthy Chinese populations. Approximately 144 participants will be enrolled and equally stratified into three age cohorts, Cohort I ages 19‐47 years, Cohort II ages 2‐6 years, and Cohort III ages 6‐12 weeks"
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	All participants were randomized according to a computer‐generated allocation schedule (Merck 2012)
Allocation concealment (selection bias)	Low risk	Allocation numbers were generated for participants; investigators, adults, and parents/guardians of children were blinded throughout trial (Merck 2012)
Blinding (performance bias and detection bias) All outcomes	Low risk	RV5 was visibly indistinguishable from placebo; investigators, study personnel (internal and external) and parents/guardians were blinded throughout trial (Merck 2012)
Incomplete outcome data (attrition bias) All outcomes	Low risk	Attrition balanced across groups with reasons reported for withdrawal
Selective reporting (reporting bias)	Low risk	All relevant outcomes reported
Other bias	Low risk	No apparent other bias