Summary of findings 1. Pneumococcal conjugate vaccine versus control vaccine for preventing acute otitis media in children.
| Pneumococcal conjugate vaccine versus control vaccine for preventing acute otitis media in children | ||||
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Patient or population: infants (predominantly < 6 months of age) and older children (aged 1 to 7 years) Settings: community (Finland, the Netherlands, the Czech Republic and Slovakia, Israel, the USA, Argentina, Colombia, and Panama) Intervention: multivalent PCVs Comparison: control vaccine | ||||
| PCV type | VE ‐ relative effect (95% CI)* | No. of participants (studies) | Certainty of evidence | Comments |
| Frequency of all‐cause acute otitis media | ||||
| CRM197‐PCV7in low‐risk infants | RRR: 6% (−4% to 16%) to 6% (4% to 9%)# | 39,530 (2 RCTs) |
⊕⊕⊕⊝ Moderatea | Results are derived from 1 very large trial including 37,868 infants, Black 2000/Fireman 2003, and 1 smaller trial including 1662 infants, Eskola 2001/Palmu 2009. |
| CRM197‐PCV7in high‐risk infants | RRR: −5% (−25% to 12%) | 944 (1 RCT) | ⊕⊕⊝⊝ Lowb | Results are derived from 1 relatively small trial with low risk of bias (O'Brien 2008). |
| OMPC‐PCV7in low‐risk infants | RRR: −1% (−12% to 10%) | 1666 (1 RCT) | ⊕⊕⊝⊝ Lowb | Results are derived from 1 trial with low risk of bias (Kilpi 2003). |
| PHiD‐CV10in low‐risk infants | RRR: 6% (−6% to 17%) to 15% (−1% to 28%) | 12,454 (2 RCTs) | ⊕⊕⊝⊝ Lowc | Results are derived from 2 trials with low, Tregnaghi 2014/Sáez‐Llorens 2017, and unclear risk of bias (Vesikari 2016/Karppinen 2019). AOM incidence rate in the control group of 1 trial, Tregnaghi 2014/Sáez‐Llorens 2017, was low compared to other studies (Table 2). |
| PHiD‐CV11in low‐risk infants | RRR: 34% (21% to 44%) | 4968 (1 RCT) | ⊕⊕⊕⊝ Moderated | Results are derived from 1 trial with low risk of bias (Prymula 2006). AOM incidence rate in the control group was low compared to other studies (Table 2). |
| Adverse effects | ||||
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CRM197‐PCV7in low‐risk infants OMPC‐PCV7in low‐risk infants PHiD‐PC10 and PHiD‐PC11 in low‐risk infants CRM197‐PCV7/9 and CRM197‐PCV7 plus TIVin older children |
Mild local reactions and fever were common in both groups, occurring more frequently in the PCV than in the control vaccine groups: redness (< 2.5 cm): 5% to 20% versus 0% to 16%, swelling (< 2.5 cm): 5% to 12% versus 0% to 8%, and fever (< 39 °C): 15% to 44% versus 8% to 25%. More severe redness (> 2.5 cm), swelling (> 2.5 cm), and fever (> 39 °C) occurred less frequently (0% to 0.9%, 0.1% to 1.3%, and 0.4% to 2.5%, respectively, in children receiving PCV) and did not differ significantly between PCV and control vaccine groups. Pain/tenderness was reported more frequently in children receiving PCV than in those receiving control vaccines: 3% to 38% versus 0% to 8%. Serious adverse events judged to be causally related to vaccination were rare and did not differ significantly between vaccine groups. No fatal serious adverse event judged to be causally related to vaccination was reported. |
77,389 (9 RCTs) | ⊕⊕⊕⊕ High | Results are derived from 9 trials with low risk of bias. |
| Frequency of pneumococcal acute otitis media | ||||
| CRM197‐PCV7in low‐risk infants | RRR: 20% (7% to 31) to 34% (21% to 45%) | 1662 (1 RCT) | ⊕⊕⊕⊕ High | Results are derived from 1 trial with low risk of bias (Eskola 2001/Palmu 2009). |
| OMPC‐PCV7in low‐risk infants | RRR: 25% (11% to 37%) | 1666 (1 RCT) | ⊕⊕⊕⊕ High | Results are derived from 1 trial with low risk of bias (Kilpi 2003). |
| PHiD‐CV10in low‐risk infants | RRR: 53% (16% to 74%) | 7359 (1 RCT) | ⊕⊕⊕⊕ High | Results are derived from 1 trial with low risk of bias (Tregnaghi 2014/Sáez‐Llorens 2017). |
| PHiD‐CV11in low‐risk infants | RRR: 52% (37% to 63%) | 4968 (1 RCT) | ⊕⊕⊕⊕ High | Results are derived from 1 trial with low risk of bias (Prymula 2006). |
| Frequency of recurrent acute otitis media (defined as 3 or more acute otitis media episodes in 6 months or 4 or more in 1 year) | ||||
| CRM197‐PCV7in low‐risk infants | RRR: 9% (−12% to 27%) to 10% (7% to 13%) | 39,530 (2 RCTs) | ⊕⊕⊕⊝ Moderatee | Results are derived from 1 very large trial including 37,868 infants, Black 2000/Fireman 2003, and 1 smaller trial including 1662 infants, Eskola 2001/Palmu 2009, both with low risk of bias. |
| PHiD‐CV11in low‐risk infants | RRR: 56% (−2% to 80%) | 4968 (1 RCT) | ⊕⊕⊝⊝ Lowf | Results are derived from 1 trial with low risk of bias (Prymula 2006). |
| *For readability purposes, absolute rates (episodes/person‐year and incidence rate differences) are displayed in Table 2. #Depending on whether the outcome was assessed by a composite of positive culture and positive pneumolysin polymerase chain reaction (PCR) or by positive culture only, or whether ITT or per‐protocol analysis was performed. | ||||
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GRADE (certainty in the evidence) High certainty: Further research is very unlikely to change our confidence in the estimate of effect. Moderate certainty: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low certainty: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low certainty: Any estimate of effect is very uncertain. | ||||
AOM: acute otitis media CI: confidence interval CRM197‐PCV7: 7‐valent pneumococcal conjugate vaccine conjugated to carrier protein CRM197 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) RCT: randomised controlled trial RRR: relative risk reduction TIV: trivalent influenza vaccine VE: vaccine efficacy
aWe downgraded the certainty of the evidence from high to moderate due to imprecise effect estimate and study limitations (risk of bias). bWe downgraded the certainty of the evidence from high to low due to the very imprecise effect estimate. cWe downgraded the certainty of the evidence from high to low due to study limitations (risk of bias) and imprecise effect estimates. dWe downgraded the certainty of the evidence from high to moderate due to indirectness of evidence (low AOM incidence rate in the control group compared to other studies, most likely due to methodological differences with other studies). eWe downgraded the certainty of the evidence from high to moderate due to imprecise effect estimate. fWe downgraded the certainty of the evidence from high to low due to imprecise effect estimate and indirectness of evidence (low AOM incidence rate in the control group compared to other studies, most likely due to methodological differences with other studies).