6. Varicella: effectiveness ‐ RCTs/CCTs.

Study ID and design	Population enrolled	Outcome	Vaccine arms n = sample size	Comparator arm n = sample size	Vaccine arm events/n	Comparator arm events/n	VE% (95% CI)
aa‐Prymula 2014 RCT	This study is the first phase (1 September 2005 to 29 June 2009) of an RCT. The study was done in 111 study centres in Europe: Czech Republic (22), Greece (11), Italy (9), Lithuania (9), Norway (5), Poland (10), Romania (9), Russia (14), Slovakia (17), and Sweden (5). An eligible participant was a healthy child aged 12 to 22 months at the time of the first vaccination; had a negative history of varicella, mumps, measles, and rubella diseases and vaccinations; and was one of the following: (1) at home with at least 1 sibling (with negative history of varicella disease and vaccination), (2) attending a child minder (where at least 1 child was without a known positive history of varicella disease and vaccination), (3) playing for more than 5 min weekly with children without a known positive history of varicella disease and vaccination, (4) registered to attend a day‐care centre from 24 months of age. An eligible participant’s parents or guardians had direct access to a telephone and were deemed by the investigator of being capable of complying with the requirements of the trial protocol.	The primary efficacy endpoint was the occurrence of confirmed varicella from 42 days after the second vaccine dose to the end of the first phase of the trial. The secondary efficacy endpoint was the occurrence of confirmed varicella graded by severity over the same time period. Varicella cases (a) All (b) Moderate/severe Follow‐up = 3 years	MMRV group: 2 doses of MMRV (Priorix‐Tetra, GSK) N = 2279 MMR+V group: 1 dose MMR (Priorix, GSK) and monovalent varicella vaccine (Varilrix, GSK) at dose 2 N = 2263	MMR group (control): 2 doses of MMR (Priorix, GSK) N = 743	MMRV (a) 37/2279 (b) 2/2279 MMR+V (a) 243/2263 (b) 37/2263	MMR (a) 201/743 (b) 117/743	MMRV (a) 94.9% (92.4% to 96.6%) (b) 99.5% (97.5% to 99.9%) MMR+V (a) 65.4% (57.2% to 72.1%) (b) 90.7% (85.9% to 93.9%) VE = (1 − HR) x 100
aa‐Henry 2018 RCT linked to aa‐Prymula 2014	Healthy children aged 12 to 22 months. n = 5803 children enrolled and vaccinated (TVC) in phase A, n = 4580 in the TVC in phase B, n = 3829 completed the study up to Year 6; n = 5289 ATP cohort for efficacy in phase A + B, n = 3791 in the ATP cohort for efficacy in phase B	Varicella cases (a) All (b) Moderate/severe (c) Severe Follow‐up = 6 years	ATP cohort for efficacy phase A + B MMRV n = 2279 MMR+V n = 2266 Phase B MMRV n = 1802 MMR+V n = 1593 MMRV group 2 doses of MMRV (Priorix‐Tetra, GSK) at Day 0 and Day 42 MMR+V group 1 dose of MMR (Priorix, GSK) at Day 0 and 1 dose of monovalent varicella vaccine (Varilrix, GSK) at Day 42	ATP cohort for efficacy phase A + B MMR n = 744 Phase B MMR n = 396 MMR group 2 doses of the MMR (Priorix, GSK) vaccine at Day 0 and Day 42	Phase A + B MMRV (a) 71/2279 (b) 6/2279 (c) 0/2270 MMR+V (a) 419/2266 (b) 58/2266 (c) 1/2266 Phase B MMRV (a) 33/1800 (b) 4/1800 (c) 0/1800 MMR+V (a) 176/1592 (b) 18/1592 (c) 0/1592	Phase A + B MMR (a) 325 /744 (b) not reported Phase B (a) 125/396 (b) not reported	Phase A + B MMRV (a) 95.0% (93.6% to 96.2%) (b) 99.0% (97.7% to 99.6%) (c) undefined MMR+V (a) 67.0% (61.8% to 71.4%) (b) 90.3% (86.9% to 92.8%) (c) 94.6% (55.3% to 99.4%) Phase B MMRV (a) 95.3% (93.1% to 96.8%) (b) 98.4% (95.5% to 99.4%) (c) undefined MMR+V (a) 69.5% (61.5% to 75.8%) (b) 91.8% (85.9% to 95.2%) (c) undefined VE = (1 − HR) x 100
aa‐Povey 2019 RCT linked to aa‐Prymula 2014	Children aged 12 to 22 months were eligible for inclusion if: had not received MMR or varicella vaccines, or both, or had measles‐mumps‐rubella or varicella zoster or herpes zoster diseases, or both, and were at home with at least 1 sibling with negative history of varicella disease and vaccination, at a child‐minders where at least 1 child was without a known positive history of varicella disease and vaccination, playing for more than 5 min/week with children without a known positive history of varicella disease and vaccination, or registered to attend day care from 24 months.	Varicella cases (a) All (b) Moderate/Severe Follow‐up = 10 years	Phase A + B MMRV n = 2279 MMR+V n = 2266 Phase B MMRV n = 1800 MMR+V n = 1591 MMRV group 2 doses of MMRV (Priorix‐Tetra, GSK) at Day 0 and Day 42 MMR+V group 1 dose of MMR (Priorix, GSK) at Day 0 and 1 dose of monovalent varicella vaccine (Varilrix, GSK) at Day 42	Phase A + B MMR n = 744 Phase B MMR n = 396 MMR group 2 doses of the MMR (Priorix, GSK) vaccine at Day 0 and Day 42	Phase A + B MMRV (a) 71/2279 (b) 6/2279 MMR+V (a) 469/2266 (b) 67/2266 Phase B MMRV (a) 33/1800 (b) 4/1800 MMR+V (a) 176/1592 (b) 18/1592	Phase A + B MMR (a) 352/744 (b) 176/744 Phase B (a) 149/396 (b) 59/396	Phase A + B MMRV (a) 95.4% (94.0% to 96.4%) (b) 99.1% (97.7% to 99.6%) MMR+V (a) 67.2% (62.3% to 71.5%) (b) 89.5% (86.1% to 92.1%) Phase B MMRV (a) 95.9% (94.1% to 97.1%) (b) 98.7% (96.4% to 99.5%) MMR+V (a) 69.8% (62.8% to 75.5%) (b) 90.0% (84.2% to 93.7%) VE = (1 − HR) x 100

ATP: according‐to‐protocol
CI: confidence interval
MMR: measles, mumps, rubella vaccine
MMRV: measles, mumps, rubella, and varicella vaccine
MMR+V: measles, mumps, rubella, and varicella vaccine
OR: odds ratio
PT: person‐time
RCT: randomised controlled trial
RR: risk ratio (relative risk)
TVC: total vaccinated cohort
VE: vaccine effectiveness/efficacy