Table 1.
Key features of studies reporting impact, efficacy or effectiveness of PHiD-CV and/or PCV13
| Author, countryref | Vaccine | Schedule | Study design | Population | Sample size | Study period | Primary outcome | Outcome source | Effect |
|---|---|---|---|---|---|---|---|---|---|
| Palmu, Finland28 | PHiD-CV | <7 m: 3 + 1 or 2 + 1 7–11 m: 2 + 1 12–18 m: 2 + 0 |
RCT double-blind cluster (FinIP) |
Children <19 m who received PHiD-CV or hepatitis control vaccine | 30,527 age <7 m enrolled. 4369 TTPs reported in 3594 children |
Feb 2009 – Dec 2011 | TTP | Nationwide database, NOMESCO, reimbursement codes | Efficacy |
| Vesikari, Finland58 | PHiD-CV | <7 m: 3 + 1 or 2 + 1 7–11 m: 2 + 1 12–18 m: 2 + 0 |
RCT double-blind cluster (nested within FinIP) |
Children 6 w-18 m who received PHiD-CV or hepatitis control vaccine | 4117 vaccinated infants for OM assessment. 6161 OM episodes | Feb 2009- Dec 2011 | OM and NPC | RCT Self-reported |
Efficacy |
| Tregnaghi, Argentina, Colombia, Panama21 | PHiD-CV | 3 + 1 | RCT double-blind | Children enrolled 6–16 w who received PHiD-CV or hepatitis control vaccine | Approximately 24,000 infants enrolled. 3602 vaccinated and 3612 controls for OM assessment | Jun 2007 – Jul 2011 | OM, pneumonia, IPD | Clinical definition | Efficacy |
| Saez-Llorens, Panama20 | PHiD-CV | 3 + 1 | RCT double-blind | Children enrolled 6–16 w who received PHiD-CV or hepatitis control vaccine | 3602 vaccinated and 3612 controls for OM, 503 with MEF collected | Aug 2007–Jul 2011 | OM and NPC | Clinical definition and laboratory result | Efficacy |
| Karppinen, Finland29 | PHiD-CV | <7 m: 3 + 1 or 2 + 1 7–11 m: 2 + 1 12–18 m: 2 + 0 |
Cohort prospective | Children <19 m enrolled in FinIP vaccine trial, 2009–2010 | 424 children. 521 episodes of RTI with OM | Apr 2008–Apr 2012 | RTI with or without OM | Clinical definition | Effectiveness |
| Pichichero, US30 | PCV7 PCV13 |
3 + 1 | Cohort prospective | Healthy children ≤30 m seen as outpatients | 239 received PCV13, 348 received PCV7 (Oct 2007–Sept 2009) | Sept 2010–Sept 2013 | OM caused by PCV13-nonPCV7 serotypes | Private practice, clinical definition and laboratory result | Effectiveness |
| Ochoa-Gondar, Spain31 | PCV7 PCV13 |
Not described | Surveillance active prospective | Children ≤14 y | 78 with pneumococcal OM | 2007–2013 | Pneumococcal OM | Population-based, laboratory confirmed | Effectiveness |
| Sohn, Korea32 | PHiD-CV PCV13 |
3 + 1 | Cohort retrospective | Children born Jan 2013–Jun 2015, mean age 32.6 m ± 8.6 m |
990,224 children, 591,529 OM cases | 2013–2016 | OM, IPD, pneumonia | Nationwide database, ICD10 | Effectiveness |
| Lau, UK33 | PCV7 PCV13 |
2 + 1 | Cohort retrospective | Children <10 y | 567,275 children (240,419 OM episodes) | 2002–2012 | OM, antibiotic prescriptions |
Nationally representative database, ICD10, reimbursement codes | Impact |
| Wiese, US34 | PCV7 PCV13 |
3 + 1 | Cohort retrospective | Children <2 y | 368,063 children (618,968 OM episodes, 24,875 TTP) | 2006–2014 | OM, TTP, recurrent OM | State-wide database, ICD9, ICD10 | Impact |
| Zhou, US35 | PCV7 PCV13 |
3 + 1 | Ecological | Children <5 y | Not described | 1997–2013 | OM | Nationally representative database, ICD9-CM | Impact |
| Kawai, US36 | PCV7 PCV13 |
3 + 1 | Cohort retrospective | Children <19 y with an OPD visit for OM | 24,148 OM-related visits | 1997–2014 | OM | Nationally representative database, ICD9 | Impact |
| Fortanier, Netherlands37 | PCV7 PHiD-CV |
3 + 1 and 2 + 1 after 2013 | Cohort retrospective | Children <5 y born 2004–2015 | 18,237 children (6967 first OM episodes) | 2004–2015 | OM | Nationwide database ICPC | Impact |
| Sigurdsson, Iceland38 | PHiD-CV | 2 + 1 | Cohort retrospective | Children <3 y born 2005–2015 | 53,150 children (58,794 OM episodes) | 2005–2015 | OM | Whole population database, ICD10 | Impact |
| Sartori, Brazil39 | PHiD-CV | 3 + 1 | Cohort retrospective | Children 2–23 m | 4793 children with 6401 OM OPD visits | Aug 2008–Jul 2015 | OM | Municipal database, ICD10 | Impact |
| Rosenblut, Chile40 | PHiD-CV | 3 + 1 (2011), 2 + 1 (from 2012) | Case-control nested | Children <24 m attending ED | OM: 1907 Controls: 244,334 |
2007–2015 | OM | Hospital database, ICD10 | Impact |
| Suarez, Peru41 | PCV7 PHiD-CV |
2 + 1 | Cohort retrospective | Children <1 y | 70,670 OM-related OPD visits | 2006–2012 | OM, pneumonia | Nationwide database, ICD10 | Impact |
| Marom, Israel42 | PCV7 PCV13 |
2 + 1 | Cohort retrospective | Children <16 y (mean 1.1–3.3 y for pneumococcal infections) hospitalized with head/neck infections | 787 head/neck infections, including 529 OM | 2007–2014 | OM, head/neck infections | Hospital database, ICD9 | Impact |
| Laursen, Denmark43 | PCV7 PCV13 |
Not described | Cohort retrospective | Children <16 y with OM hospitalization or mastoiditis (median age 14–29 m) |
246 cases of complicated OM | 2001–2015 | Complicated OM | Hospital ENT clinic database | Impact |
| Tawfik, US44 | PCV7 PCV13 |
3 + 1 | Cohort retrospective | Hospitalized children mean age 4.5–7.1 y with OM/complicated OM | >7,000,000 hospitalizations annually. 3343 for OM/complicated OM in 2000, 2279 in 2012 |
2000–2012 | OM/complicated OM | Nationally representative database, ICD9 | Impact |
| Fortunato, Italy45 | PCV7 PCV13 |
2 + 1 | Case-control matched | Children <5 y hospitalized for OM | 28 pediatric wards | 2006–2012 | OM, IPD, pneumonia | Nationwide database, ICD9 | Impact |
| Leach, Australia46 | PCV7 PHiD-CV |
3 + 1 | Surveillance active prospective | Aboriginal children <6 y | 895 (451 PHID-CV vaccinated, 444 PCV7 vaccinated)** | Sep 2008–Dec 2012 | OM | Clinical definition and laboratory result | Impact |
| Sigurdsson, Iceland47 | PHiD-CV | 2 + 1 | Cohort retrospective | Children <3 y born 2005–2015 | 51,264 children (256 children OM hospitalized, 280 OM hospitalizations) | 2005–2016 | OM, IPD, pneumonia, sepsis, meningitis | Hospital database, ICD10 | Impact |
| Petousis-Harris, New Zealand48 | PCV7 PHiD-CV PCV13 |
3 + 1 | Cohort retrospective | Children born 2006–2015, <6 y | 44,545 hospitalized for OM | 2006–2015 | OM, IPD, pneumonia | Database, ICD10 | Impact |
| Ben-Shimol, Israel49 | PCV7 PCV13 | 2 + 1 | Surveillance active prospective | Children <3 y with OM resulting in MEF culture | 7705 OM episodes with MEF culture | Jul 2004–Jun 2016 | Complex OM | Hospital laboratory result | Impact |
| Ben-Shimol, Israel50 | PCV7 PCV13 |
2 + 1 | Surveillance active prospective | Children <3 y with OM resulting in MEF culture | 7475 OM episodes with MEF culture | Jul 2004–Jun 2015 | Complex OM | Hospital laboratory result | Impact |
| Ben-Shimol, Israel51 | PCV7 PCV13 |
2 + 1 | Surveillance active prospective | Children <2 y with OM resulting in MEF culture | 6122 OM episodes with MEF culture | Jul 2004–Jun 2013 | Complex OM | Hospital laboratory result | Impact |
| Palmu, Finland52 | PHiD-CV | 2 +1 | Cohort retrospective | Vaccine eligible 3–54 m old children | unknown | Jun 2010–Sept 2014 | TTP, antibiotic purchases (OM) | Nationwide database, NOMESCO, reimbursement codes | Impact |
| Eythorsson, Iceland53 | PHiD-CV | 2 + 1 | Cohort retrospective | Children <5 y born 2005–2015 | 51,247 children (14,351 underwent 20,373 procedures) | 2005–2016 | TTP | Whole population database reimbursement codes | Impact |
| Gisselsson-Solen, Sweden54 | PCV7 PHiD-CV PCV13 |
2 + 1 | Cohort retrospective | Children <4 y with OM-related diagnosis | 21 Swedish regions | 2005–2014 | OM and TTP | Whole population database, ICD10 | Comparison |
| Edmondson-Jones, Sweden55 | PCV7 PHiD-CV PCV13 |
2 + 1 | Cohort retrospective | ≤5 y living in Skåne (PCV7 then PHiD-CV) or VGR (PCV7 then PCV13) | 191,596 born in Skåne, 250,327 born in VGR; 1999–2013 | 2005–2013 | OM | Regional database, ICD10 | Comparison |
| Leach, Australia56 | PHiD-CV PCV13 |
3 + 1 | Surveillance active prospective | Aboriginal children <6 y | 651 (511 PHID-CV vaccinated, 140 PCV13 vaccinated)* | Feb 2010– Aug 2013 |
OM, NPC | Clinical definition and laboratory result | Comparison |
| Lee, Korea57 | PHiD-CV PCV13 |
3 + 1 | Cohort prospective | Healthy infants enrolled <2 m who visited 8 hospitals | 305 children, 182 received PCV13, 123 received PHiD-CV |
Nov 2014– May 2019 |
OM, NPC | Hospital clinical definition | Comparison |
ED, emergency department; ENT, ear-nose-throat; FinIP, Finnish Invasive Pneumococcal trial; ICD, International Classification of Diseases; ICD-CM, International Classification of Diseases, Clinical Modification; ICPC, International Classification of Primary Care; IPD, invasive pneumococcal disease; m, months of age; MEF, middle ear fluid; NOMESCO, Nordic Medico-Statistical Committee; NPC, nasopharyngeal carriage; OM, otitis media/acute otitis media; OPD, outpatient department; PCV7/PCV13, 7- or 13-valent pneumococcal conjugate vaccines; PHiD-CV, pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine; RCT, randomized controlled trial; RTI, respiratory tract infection; TTP, tympanostomy tube placement; VGR, Västra Götalandsregionen, w, weeks of age; y, years of age.
*Children were vaccinated with at least 2 doses of PCV13 or PHiD-CV (no more than 1 dose of the other vaccine).
**Children were vaccinated with at least 2 doses of PCV7 or PHiD-CV (no more than 1 dose of the other vaccine).