. 2020 Nov 24;2020(11):CD001480. doi: 10.1002/14651858.CD001480.pub6

1. Effect of pneumococcal conjugate vaccination on frequency of all‐cause acute otitis media episodes.

	Intention‐to‐treat				Per‐protocol
	Episodes/person‐year		Incidence rate difference ‐ episodes per person‐year (95% CI)	VE expressed as relative reduction in risk (95% CI)^a	Episodes/person‐year		Incidence rate difference ‐ episodes per person‐year (95% CI)	VE expressed as relative reduction in risk (95% CI)^a
	Treatment	Control		VE expressed as relative reduction in risk (95% CI)^a	Treatment	Control		VE expressed as relative reduction in risk (95% CI)^a
PCV administered in early infancy
*CRM197‐PCV7*
Black 2000 Fireman 2003	‐ ‐	‐ ‐	‐ ‐	6% (4% to 9%) 6% (4% to 8%)	‐ ‐	‐ ‐	‐ ‐	7% (4% to 10%) 7% (4% to 9%)
Eskola 2001	‐	‐	‐	‐	1.16	1.24	−0.08^d	6% (−4% to 16%)
O'Brien 2008^b	1.43	1.36	0.07 (−0.05 to 0.18)	−5% (−25% to 12%)^c	1.35	1.35	0.00 (−0.13 to 0.14)	0% (−21% to 17%)
*OMPC‐PCV7*
Kilpi 2003	‐	‐	‐	‐	‐	‐	‐	−1%^h (−12% to 10%)
*PHiD‐PC10 and PHiD‐PC11*
Tregnaghi 2014 Sáez‐Llorens 2017	0.03	0.04	−0.01 (−0.01 to 0.00)	15% (−1% to 28%)	‐	‐	‐	13% (−5% to 28%)
Vesikari 2016^b Karppinen 2019^e	‐  ‐	‐  ‐	‐  ‐	‐  ‐	0.99  1.0	1.01  1.3	−0.02^d  −0.3 (−0.7 to 0.1)	6% (−6% to 17%) 23% (0% to 40%)
Prymula 2006	‐	‐	‐	‐	0.08	0.13	−0.04^d	34% (21% to 44%)
PCV administered at a later age
*CRM197‐PCV7 followed by PPV23*
Veenhoven 2003	‐	‐	‐	−25% (−57% to 1%)	1.1	0.83	−0.27^d	−29%^h (−62% to −2%)
van Kempen 2006	‐	‐	‐	‐	0.78	0.67	−0.11^d	−16%^h (−96% to 31%)
*CRM197‐PCV7/TIV*
Jansen 2008	‐	‐	‐	‐	‐	‐	‐	57% (6% to 80%)^f
*CRM197‐PCV9*
Dagan 2001	‐	‐	‐	‐	0.66	0.79	−0.14 (−0.29 to 0.02)	17% (−2% to 33%)

CI: confidence interval CRM197‐PCV7: 7‐valent pneumococcal conjugate vaccine conjugated to carrier protein CRM197 CRM197‐PCV7/TIV: trivalent influenza vaccine plus 7‐valent pneumococcal conjugate vaccine conjugated to carrier protein CRM197 CRM197‐PCV9: 9‐valent pneumococcal conjugate vaccine conjugated to carrier protein CRM197 HBV: hepatitis B virus OMPC‐PCV7: 7‐valent pneumococcal conjugate vaccine conjugated to the outer membrane protein complex of Neisseria meningitidis serogroup B PCV: pneumococcal conjugate vaccine PHiD‐CV10: 10‐valent pneumococcal conjugate vaccine conjugated to protein D (surface lipoprotein of non‐typeable Haemophilus influenzae) PHiD‐CV11: 11‐valent pneumococcal conjugate vaccine conjugated to protein D (surface lipoprotein of non‐typeable Haemophilus influenzae) PPV23: 23‐valent pneumococcal polysaccharide vaccine TIV: trivalent influenza vaccine VE: vaccine efficacy

^aPositive effect estimates indicate a relative reduction in the risk (e.g. 6% means that the vaccine reduces the risk by 6%); negative effect estimates indicate a relative increase in the risk (e.g. −5% means that the vaccine increases the risk by 5%). ^bCluster‐randomised controlled trial. ^cDefined as primary efficacy analysis. Analysis is not entirely according to intention‐to‐treat principle, as 88/944 children were not included in the analysis due to not meeting strict chart review criteria. ^d95% CI could not be calculated, as person‐time across treatment groups was not reported. ^eRespiratory tract infections with acute otitis media was used as the outcome measure. The PHiD‐CV10 and control vaccine groups were statistically different from each other in terms of type of residential area, presence of older siblings, and socioeconomic status of the family. ^fIndex group: CRM197‐PCV7/TIV, control: HBV/placebo; VE placebo/TIV versus HBV/placebo: 71% (95% CI 30% to 88%), that is larger VE placebo/TIV versus HBV/placebo than CRM197‐PCV7/TIV versus HBV/placebo. ^hnegative values for VE expressed as relative reduction in risk represent an increase in the risk for acute otitis media.