GRADE: 15-valent pneumococcal conjugate vaccine (PCV15) use in children aged <2 years

About

CDC vaccine recommendations are developed using an explicit evidence-based method based on the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach.

Introduction

On June 22, 2022, ACIP recommended use of 15-valent pneumococcal conjugate vaccine (PCV15 [Vaxneuvance, Merck Sharp & Dohme LLC]) as an option for pneumococcal conjugate vaccination for persons aged <19 years according to currently recommended PCV13 dosing and schedules. A systematic review and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach was employed to guide ACIP’s deliberations regarding use of this vaccine.

Methods

A systematic literature search was completed to review all available evidence on the immunogenicity and safety of PCV15 among pediatric age groups for which the vaccine was approved. Since only immunogenicity and safety data were available for PCV15, the search included 13-valent pneumococcal conjugate vaccine (PCV13 [Prevnar 13, Wyeth Pharmaceuticals, Inc., a subsidiary of Pfizer, Inc.]) efficacy or effectiveness studies to help interpret PCV15 immunogenicity study findings. GRADE assessment was performed for PCV15 studies only. As a basis for the GRADE evidence assessment, the policy question consisting of the population, intervention, comparison, and outcomes of interest was defined (Table 1).

Table 1: Policy Question and PICO

Policy question:
Should PCV15 be routinely recommended for U.S. children <2 years of age as an option for pneumococcal conjugate vaccination according to currently recommended dosing and schedules?
Population
U.S. children <2 years of age
Intervention
PCV15 according to dosing and schedules currently recommended for PCV13
Comparison
PCV13 according to currently recommended dosing and schedules
Outcomes
Vaccine-type invasive pneumococcal disease, vaccine-type pneumonia, vaccine-type acute otitis media, vaccine-type pneumococcal deaths, serious adverse events following immunization

This systematic review leveraged strategies used in existing systematic reviews, which captured literature published between January 1994–December 2019 targeting PCV7, PCV10, and PCV13 using various dosing schedules in the general pediatric population. Specifically, we utilized:

  • Systematic Review of Pneumococcal Conjugate Vaccine Dosing Schedules (Loo 2014); searched literature from January 1994 – September 2010
  • Systematic Review of Pneumococcal Conjugate Vaccine Dosing Schedules and Products (Cohen 2017); searched literature from October 2010 – December 2016
  • Updated literature search to Cohen 2017, which was conducted to review evidence regarding dosing schedule changes; searched literature from January 2017 – December 2019

In addition, we conducted a search of literature published during January 2010 – October 2021 from the following databases: Medline (OVID), Embase (OVID), Cochrane Library, CINAHL (EbscoHost), and Scopus (for WOS). The search terms are included in Appendix 1. The updated search sought to capture:

  • Pneumococcal vaccine studies specifically targeting children with underlying medical conditions*, which were not captured in the previous literature searches
  • Additional literature on pneumococcal vaccines published since January 2020 to update the previous systematic reviews evaluating PCV13 use in the general pediatric population

Search results were supplemented by an updated Pubmed search using “V114**” or “PCV15” and a search of clinicaltrials.gov using “V114”. Unpublished data were provided by the vaccine manufacturer.

Studies with primary data on PCV15 use in children <2 years were included . Seventy-one studies were initially identified; after screening, deduplication, and exclusion, 7 were included for GRADE. Characteristics of these studied are included in Appendix 2. No PCV15 studies directly assessed vaccine effectiveness against the critical outcomes. Beneficial and harmful outcomes for the GRADE assessment were selected by the ACIP Pneumococcal Vaccines Work Group during calls and via an email survey in which Work Group members were asked to rank the relative importance of each outcome. Vaccine-type invasive pneumococcal disease, vaccine-type non-bacteremic pneumococcal pneumonia, vaccine-type acute otitis media, vaccine-type pneumococcal deaths, and serious adverse events (SAEs) following immunization were deemed to be critical outcomes (Table 2).

*Underlying medical conditions include cerebrospinal fluid leak; chronic heart disease; chronic lung disease; cochlear implant; diabetes mellitus; immunocompromising conditions (chronic renal failure or nephrotic syndrome; congenital or acquired asplenia or splenic dysfunction; congenital or acquired immunodeficiencies; diseases and conditions treated with immunosuppressive drugs or radiation therapy, including malignant neoplasms, leukemias, lymphomas, Hodgkin disease, and solid organ transplant; HIV infection; and sickle cell disease and other hemoglobinopathies).

**V114 is the name used for Merck’s investigational 15-valent pneumococcal conjugate vaccine candidate

Table 2: Outcomes and Rankings

Outcome Importance* Included in evidence profile
Vaccine-type invasive pneumococcal disease Critical No**
Vaccine-type pneumonia Critical No**
Vaccine-type acute otitis media Critical No**
Vaccine-type pneumococcal deaths Critical No**
Serious adverse events following immunization Critical Yes

*Three options: 1. Critical; 2. Important but not critical; 3. Not important for decision making
**No clinical evidence available; immunogenicity data used as proxy for vaccine effectiveness of outcomes

Table 3a. Summary of Studies Reporting Immunogenicity

Author, year Study design; population and age Intervention N intervention N comparison Comparator vaccine IgG GMC ratios [range (serotype)]1 Absolute difference in % seroresponders (serotype)2 Interpretation Study limitations (Risk of Bias)
Platt, 2020
(V114-008)		 Phase 2 RCT (proof of concept); healthy children, 6––12 weeks PCV15
3+1 (2,4, 6, 12––15m)		 350 (Lot 1)
347 (Lot 2)		 347 PCV13 Post-dose 3
Lot 1: 0.54 (6A) to 1.98 (3)
Lot 2: 0.57 (6A) to 1.93 (3)
Post-dose 4
Lot 1: 0.67 (7F) to 1.44 (3)
Lot 2: 0.66 (6A) to 1.48 (3)		 Post-dose 3
Lot 1: -5.6 (6A) to 24.3 (3)
Lot 2: -0.8 (19F) to 22.4 (3)
Post-dose 4
Lot 1: -1.1 (23F) to 8.6 (3)
Lot 2: 0 (4, 5, 6A, 7F, 9V, 14, 18C) to 9.6 (3)		 GMC ratios
Post-dose 3
  1. PCV15 > PCV13 for 3/13 (Lot 1) and 4/13 (Lot 2) shared serotypes; significantly higher for st3 (Lot 1 and 2) and 23F (Lot 2)
  2. PCV15 (Lot 1 and 2) > PCV13 for 22F and 33F

Post-dose 4

  1. PCV15 > PCV13 for st3 and 6B (Lot 1) and st3 and 18 (Lot 2); significantly higher for st3 only (Lot 1 and 2)
  2. PCV15 (Lot 1 and 2) > PCV13 for 22F and 33F

%seroresponders
Post-dose 3

  1. PCV15 (Lot 1 and Lot 2) noninferior3 to PCV13 for all 13 shared serotypes
  2. PCV15 > PCV13 for 9/13 (Lot 1) and 8/13 (Lot 2) shared st; significantly higher for st3 only (Lot 1 and 2)
  3. PCV15 (Lot 1 and 2) > PCV13 for 22F and 33F

Post-dose 4

  1. PCV15 > PCV13 for 5/13 (Lot 1) and 6/13 (Lot 2) shared st; significantly higher for st3 only (Lot 1 and 2)
  2. PCV15 = PCV13 for 5/13 (Lot 1) and 7/13 (Lot 2) shared st
  3. PCV15 (Lot 1 and 2) > PCV13 for 22F and 33F
 Not serious
V114-029
Merck, unpublished		 Phase 3 RCT (pivotal study); healthy children, 42––90 days PCV15
3+1 (2,4, 6, 12–15m); co-administration Pentacel, RECOMBIVAX HB, RotaTeq		 858 856 PCV13 Post-dose 3:
0.52 (6A) to 1.73 (3)
Post-dose 4:
0.60 (6A) to 1.35 (3)		 Post-dose 3
-5 (6A) to 16 (3)
Post-dose 4
Not reported		 GMC ratios
Post-dose 3
  1. PCV15 noninferior4 to PCV13 for 12/13 (no for 6A) shared serotypes; statistically significantly higher for st3
  2. PCV15 statistically significantly higher to PCV13 for 22F and 33F (unique st)
  3. PCV15 > PCV13 for st3 only (statistically significant)
  4. PCV15 > PCV13 for 22F and 33F

Post-dose 4

  1. PCV15 noninferior4 to PCV13 for all 13 shared serotypes; statistically significantly higher for st3
  2. PCV15 statistically significantly higher to PCV13 for 22F and 33F (unique st)
  3. Non-inferiority met for concomitant use
  4. PCV15 > PCV13 for st3 (statistically significant)
  5. PCV15 > PCV13 for 22F and 33F

%seroresponders
Post-dose 3

  1. PCV15 noninferior5 to PCV13 for all 13 shared serotypes; statistically significantly higher for st3
  2. PCV15 statistically significantly higher to PCV13 for 22F and 33F (unique st)
  3. PCV15 > PCV13 for st 3 (statistically significant)
  4. PCV15 = PCV13 for 14 and 23F
  5. PCV15 > PCV13 for 22F and 33F

Post-dose 4

  1. Not reported
 Not serious
V114-027
Merck, unpublished		 Phase 3 RCT (product interchangeability); healthy children, 42–90 days Group 2: PCV13 + PCV13 + PCV13 + PCV15 181 179 Group 1: PCV13 @ 2,4,6, 12–15m 0.83 (1) to 1.51 (18C) 0 (6A, 7F, 9V, 14, 19F) to 6.5 (23F) GMC ratio (post-dose 4):
  1. Group 2 > Group 1 for 7/13 shared st; significant for 6B, 14, 18C

% seroresponders (post-dose 3):

  1. Group 2 > Group 1 for 8/13 shared st; significant for 14 and 23F
  2. Group 2 = Group 1 for 5/13 st
  3. Group 2 >Group 1 for 33F
 Not serious
Group 3: PCV13 + PCV13 + PCV15 + PCV15 178 179 Group 1: PCV13 @ 2,4,6, 12–15m 0.84 (4 and 19A) to 1.44 (18C) -4.9 (4) to 5.9 (3) GMC ratio (post-dose 4):
  1. Group 3 > Group 1 for 6/13 shared st; significant for 14 and 18C

% seroresponders (post-dose 3):

  1. Group 3 > Group 1 for 4/13 shared st; significant for st4
  2. Group 3 = Group 1 for 7F
  3. Group 3 >Group 1 for 22F and 33F
Group 4: PCV13 + PCV15 + PCV15 + PCV15 179 179 Group 1: PCV13 @ 2,4,6, 12–15m 0.77 (23F) to 1.08 (6B) -91.4 (23F) to 8.7 (3 and 6B) GMC ratio (post-dose 4):
  1. Group 4 > Group 1 for 4/13 shared st

% seroresponders (post-dose 3):

  1. Group 4 > Group 1 for 5/13 shared st; significant for st3
  2. Group 4 > Underlying medical conditions include cerebrospinal fluid leak; chronic heart disease; chronic lung disease; cochlear implant; diabetes mellitus; immunocompromising conditions (chronic renal failure or nephrotic syndrome; congenital or acquired asplenia or splenic dysfunction; congenital or acquired immunodeficiencies; diseases and conditions treated with immunosuppressive drugs or radiation therapy, including malignant neoplasms, leukemias, lymphomas, Hodgkin disease, and solid organ transplant; HIV infection; and sickle cell disease and other hemoglobinopathies). noninferior3Group 1 for 22F
Group 5: PCV15 @ 2,4,6, 12–15m 179 179 Group 1: PCV13 @ 2,4,6, 12–15m 0.67 (7F) to 1.22 (3) -4.7 (19A) to 20.7 (3) GMC ratio (post-dose 4):
  1. Group 5 > Group 1 for 2/13 shared st; significant for st3

% seroresponders (post-dose 3):

  1. Group 5 > Group 1 for 6/13 shared st; significant for st3
  2. Group 5 > Group 1 for 22F and 33F
V114-024
Merck, unpublished		 Phase 3 RCT (catch up); heathy children, 7 months – 17 years PCV15 (7–11m: 3 doses (dose 1 @ 0w, dose 2 @ 4–8w PD1, dose 3 @ 8–12w PD2 AND >12m)) 64 64 PCV13 (3 doses) 0.52 (6A) to 1.55 (3) -3.3 (6A and 6B) to 3.4 (3) GMC ratio (post-dose 3):
  1. PCV15 > PCV13 for st3 (significant)
  2. PCV15 >PCV13 for 22F and 33F

% seroresponders (post-dose 3):

  1. PCV15 > PCV13 for st3
  2. PCV15 = PCV13 for 8/13 shared st
  3. PCV15 >PCV13 for 22F and 33F
 Not serious
PCV15 (12–23m: 2 doses (dose 1 @ 0w, dose 2 @ 4–8w PD1)) 62 64 PCV13 (2 doses) 0.54 (6A) to 1.76 (3) -11.1 (6A) to 8.2 (3) GMC ratio (post-dose 2):
  1. PCV15 > PCV13 for 5/13 shared st; significant for st3 and 18C
  2. PCV15 >PCV13 for 22F and 33F

% seroresponders (post-dose 2):

  1. PCV15 > PCV13 for 6/13 shared st; significant for st3 and 4
  2. PCV15 = PCV13 for 19F
  3. PCV15 >PCV13 for 22F and 33F
PCV15 (2–17y: 1 dose (>8w after previous PCV) 177 175 PCV13 (1 dose) 0.48 (4) to 1.60 (18C) -1.2 (4) to 8 (3) GMC ratio (post-dose 1):
  1. PCV15 > PCV13 for 6/13 shared st; significant for st3 and 18C
  2. PCV15 >PCV13 for 22F and 33F

% seroresponders (post-dose 1):

  1. PCV15 > PCV13 for 5/13 shared st; significant for st3
  2. PCV15= PCV13 for 4/13 st
  3. PCV15 >PCV13 for 22F and 33F

RCT = randomized controlled trial; GMC = Geometric Mean Concentration; st = serotype; PCV15 > PCV13 = PCV15 had higher immune responses compared to PCV13

  1. Ratio calculated as [GMC (PCV15)]/[GMC (comparator vaccine)]; blood draws occurred 30 days or 1 month post-dose.
  2. Seroresponse: proportion of participants meeting IgG threshold value of >=0.35μg/mL; blood draws occurred 30 days or 1 month post-dose.
  3. The statistical criterion for noninferiority corresponds to the lower bound of the adjusted 95% confidence interval (CI) of the proportion difference (V114 − PCV13) being greater than −0.15 for each of the 13 shared serotypes.
  4. Noninferiority requires the lower bound of the 2-sided 95% CI for IgG GMC ratio (V114/PCV13) to be >0.5 (1-sided p-value <0.025)
  5. Noninferiority requires the lower bound of the 2-sided 95% CI for the difference in response rates (V114 –PCV13) to be >-10 percentage points (1-sided p-value <0.025)

Table 3b. Summary of Studies Reporting Safety

Author, year Study Design; population and age N intervention N comparison Comparator vaccine Absolute % difference
(% SAE PCV15 –
% SAE comparator)*		 N related to vaccine Study limitations (Risk of Bias)
Platt, 2020
(V114-008)		 Phase 2 RCT (proof of concept); healthy children, 6–12 weeks 697 (lots 1 and 2 combined) 347 PCV13 1 2 Not serious
V114-029
Merck, unpublished		 Phase 3 RCT (pivotal study); healthy children, 42–90 days 858 855 PCV13 0.8 0 Not serious
V114-027
Merck, unpublished		 Phase 3 RCT (product interchangeability); healthy children, 42–90 days Group 2: PCV13 + PCV13 + PCV13 + PCV15 (booster) 181 179 Group 1: PCV13 @ 2,4,6, 12–15m 1.6 0 Not serious
Group 3: PCV13 + PCV13 + PCV15 + PCV15 178 179 Group 1: PCV13 @ 2,4,6, 12–15m -3.3** 1**
Group 4: PCV13 + PCV15 + PCV15 + PCV15 179 179 Group 1: PCV13 @ 2,4,6, 12–15m -1.6 0
Group 5: PCV15 @ 2,4,6, 12–15m 179 179 Group 1: PCV13 @ 2,4,6, 12–15m 0 0
V114-024
Merck, unpublished		 Phase 3 RCT (catch up); heathy children, 7 months – 17 years PCV15 (7–11m: 3 doses (dose 1 @ 0w, dose 2 @ 4–8w PD1, dose 3 @ 8–12w PD2 AND >12m)) 64 64 PCV13 (3 doses) 3.1 0 Not serious
PCV15 (12–23m: 2 doses (dose 1 @ 0w, dose 2 @ 4–8w PD1)) 62 64 PCV13 (2 doses) 0.2 0
PCV15 (2–17y: 1 dose (>8w after previous PCV)) 177 175 PCV13 (1 dose) 0 0
V114-031
Merck, unpublished		 Phase 3 RCT, full-term v. preterm infants, 41 – 90 days 1965 433 PCV13 -0.6 2 Not serious

SAE = Serious adverse event following immunization; RCT = randomized controlled trial; PCV13 = 13-valent pneumococcal conjugate vaccine; PCV15 = 15-valent pneumococcal conjugate vaccine
*Reported serious adverse events include those that occurred after dose 1 through completion of study participation.

** SAE that occurred in Group 3 occurred after the second PCV13 dose. Merck data on file, P027 clinical study report section 16.2.7.1.3: listing of participants with serious adverse events. Charlotte, NC: Merck Sharp & Dohme LLC; 2021

Table 4. Grade Summary of Findings Table

\
Certainty assessment № of patients Results Certainty Importance
№ of studies Study design Risk of bias Inconsistency Indirectness Imprecision Other considerations PCV15
Intervention		 PCV13
comparison		 Relative
(95% CI)		 Absolute
(95% CI)
Vaccine effectiveness: vaccine-type pneumococcal disease (assessed with immunogenicity data)
41-4 Randomized studies Not serious Not serious Seriousa Not serious Not serious 2575 1685 PCV15 noninferior to PCV13 for all 13 shared serotypes; statistically significantly higher immune response for st3

PCV15 statistically significantly higher immune responses to PCV13 for 22F and 33F (unique st)

 2 Critical
Serious adverse events following immunization
51-5 Randomized studies Not serious Not serious Very seriousb Not serious Not serious 4/4540 0/2117 1.7 (0.19, 14.2)c -- 3 Critical

No = number; PCV15 = 15-valent pneumococcal conjugate vaccine; PCV13 = 13-valent pneumococcal conjugate vaccine; st = serotype

a. These are all immunogenicity studies and there are no correlates of protection for some critical outcomes considered
b. Few vaccine-related serious adverse events reported; wide 95% CI of the relative risk cannot exclude the potential for increased harm or benefit
c. Pooled estimate is based on V114-008 and V114-031 that had SAE reported. V114-027 was not included in the pooled estimate, since the SAE occurred in a group that received PCV15, but after receipt of PCV13 doses. Merck data on file, P027 clinical study report section 16.2.7.1.3: listing of participants with serious adverse events. Charlotte, NC: Merck Sharp & Dohme LLC; 2021

Table 5. Summary of Evidence for Outcomes of Interest

Outcome Importance Included in profile Certainty
VT- invasive pneumococcal disease Critical No* 2
VT- pneumonia Critical No* 2
Vaccine-type acute otitis media Critical No* 2
Vaccine-type pneumococcal deaths Critical No* 2
Serious adverse events following immunization Critical Yes 3

*No clinical evidence available; immunogenicity data used as proxy for vaccine effectiveness of outcomes

Summary

The evidence type for use of PCV15 in children aged <2 years was determined to be 2 (moderate certainty of evidence) for VT-invasive pneumococcal disease, VT-pneumonia, VT-acute otitis media, and VT- pneumococcal deaths and was downgraded once for indirectness due to lack of correlates of protection for the critical outcomes considered. The evidence type for serious adverse events following immunization was 3 (low certainty of evidence); the evidence level for imprecision was downgraded two points to very serious for few vaccine-related serious adverse events reported and for the relative risk crossing 1. ACIP reviewed the results of both the GRADE evidence assessment and the Evidence to Recommendations (EtR) framework in February 2022. An updated EtR table was shared with ACIP in June 2022. On June 22, 2022, ACIP recommended use of PCV15 as an option for pneumococcal conjugate vaccination for persons aged <19 years according to currently recommended PCV13 dosing and schedules.

References

Loo JD, Conklin L, Deloria Knoll M, Fleming-Dutra K, et al. Methods for a Systematic Review of Pneumococcal Conjugate Vaccine Dosing Schedules. PIDJ. 2014; 33(1,S2); S182-S187.

Cohen OG. Pneumococcal Conjugate Vaccine (PCV) Product Assessment. Accessed August 2, 2021 at https://www.jhsph.edu/ivac/wp-content/uploads/2018/05/pcv-product-assessment-april-25-2017.pdf.

Platt HL, Greenberg D, Tapiero B, Clifford RA, Klein NP, Hurley DC. A Phase II Trial of Safety, Tolerability and Immunogenicity of V114, a 15-Valent Pneumococcal Conjugate Vaccine, Compared With 13-Valent Pneumococcal Conjugate Vaccine in Healthy Infants. Pediatric Infectious Diseases Journal 2020.

V114-029. Safety, Tolerability, and Immunogenicity of V114 in Healthy Infants (V114-029)

V114-027. A Study to Evaluate the Interchangeability of V114 and Prevnar 13™ in Healthy Infants (V114-027/PNEU-DIRECTION)

V114-024. Safety and Immunogenicity of Catch-up Vaccination Regimens of V114 (V114-024)

V114-031. A Study to Evaluate the Safety and Tolerability of V114 and Prevnar 13™ in Healthy Infants (V114-031/PNEU-LINK)

Appendices

Appendix 1. Search strategy

Database Strategy Run Date Records
Medline
(OVID)
1946–		 (((pneumococcal OR pneumococci OR streptococcus pneumoni* OR s? pneumoni*) ADJ5 (vaccin* OR immunization* OR immunisation*)) OR pneumovax OR pnu immune vaccine* OR pnuimmune vaccine* OR ppv23 OR “ppv 23” OR “23 valent” OR “23valent”)
AND
Exp Child/ OR (Child* OR pediatric* OR paediatric*).ti,ab,kf,hw.
AND
Trial* OR study OR studies OR rct* OR review.ti,pt.
Limit English; 2010 –		 10/20/2021 2864
Embase
(OVID)
1988–		 (((pneumococcal OR pneumococci OR streptococcus pneumoni* OR s? pneumoni*) ADJ5 (vaccin* OR immunization* OR immunisation*)) OR pneumovax OR pnu immune vaccine* OR pnuimmune vaccine* OR ppv23 OR “ppv 23” OR “23 valent” OR “23valent”)
AND
Exp Child/ OR (Child* OR pediatric* OR paediatric*).ti,ab,kw,hw.
AND
Trial* OR study OR studies OR rct* OR review.ti,pt.
NOT
exp animal/ NOT exp human/Limit English; 2010 – ; not pubmed/medline ; not conference abstracts		 10/20/2021 3236

-2304
duplicates

=932
unique items

Cochrane Library [mh “pneumococcal vaccines”] OR (((pneumococcal OR pneumococci OR streptococcus pneumoni* OR s? pneumoni*) ADJ5 (vaccin* OR immunization* OR immunisation*)) OR pneumovax OR pnu immune vaccine* OR pnuimmune vaccine* OR ppv23 OR “ppv 23” OR “23 valent” OR “23valent”):ti,ab
AND
[mh Child] OR (Child* OR pediatric* OR paediatric*):ti,abLimit English; 2010 –		 10/20/2021 331

-192
duplicates

=139
unique items

CINAHL
(EbscoHost)		 (((pneumococcal OR pneumococci OR “streptococcus pneumoni*” OR “s? pneumoni*”) N5 (vaccin* OR immunization* OR immunisation*)) OR pneumovax OR “pnu immune vaccine*” OR “pnuimmune vaccine*” OR ppv23 OR “ppv 23” OR “23 valent” OR “23valent”)
AND
(Child* OR pediatric* OR paediatric*)
Limit English; 2010 – ; exclude Medline records		 10/20/2021 345

-267
duplicates

=78
unique items

Scopus TITLE-ABS-KEY(((pneumococcal OR pneumococci OR “streptococcus pneumoni*” OR “s? pneumoni*”) W/5 (vaccin* OR immunization* OR immunisation*)) OR pneumovax OR “pnu immune vaccine*” OR “pnuimmune vaccine*” OR ppv23 OR “ppv 23” OR “23 valent” OR “23valent”) AND TITLE-ABS-KEY(Child* OR pediatric* OR paediatric*) AND NOT INDEX(medline)
Limit English; 2010 – ;		 10/20/2021 682

-492
duplicates

=190
unique items

Appendix 2. Studies Included in the Review of Evidence

Author, year Study design Intervention Country Age Total population N Intervention N comparison Outcomes Funding source
Platt, 2020
(V114-008)		 Phase 2 RCT (proof of concept); healthy children PCV15
3+1 (2,4, 6, 12–15m)		 Canada, Denmark, Finland, Israel, Spain, US 6–12 weeks at enrollment 1044 350 (Lot 1)
347 (Lot 2)		 347 Immunogenicity, safety Merck
V114-029
Merck, unpublished		 Phase 3 RCT (pivotal study); healthy children PCV15
3+1 (2,4, 6, 12–15m); co-administration Pentacel, RECOMBIVAX HB, RotaTeq		 Puerto Rico, Thailand, Turkey, US 42–90 days at enrollment 1714 858 856 Immunogenicity, safety Merck
V114-027
Merck, unpublished		 Phase 3 RCT (product interchangeability); healthy children Group 1: PCV13 @ 2,4,6, 12–15m
Group 2: PCV13 + PCV13 + PCV13 + PCV15 (booster)
Group 3: PCV13 + PCV13 + PCV15 + PCV15 (booster)
Group 4: PCV13 + PCV15 + PCV15 + PCV15 (booster)
Group 5: PCV15 @ 2,4,6, 12–15m		 Puerto Rico, Thailand, Turkey, US 42–90 days at enrollment 896 Group 2 (n=181)
Group 3 (n=178)
Group 4
(n=179)
Group 5
(n=179)		 Group 1 (n=179) Immunogenicity, safety Merck
V114-024
Merck, unpublished		 Phase 3 RCT (catch up); healthy children 7–11m: 3 doses (dose 1 @ 0w, dose 2 @ 4–8w PD1, dose 3 @ 8–12w PD2 AND >12m
12–23m: 2 doses (dose 1 @ 0w, dose 2 @ 4–8w PD1)
2–17y: 1 dose (>8w after previous PCV)		 Finland, Malaysia, Poland, Russia, Thailand 7 months – 17 years 606 2–11m (n=64)
12–23m (n=62)
2–17y
(n=177)		 2–11m (n=64)
12–23m (n=64)
2–17y
(n=175)		 Immunogenicity, safety Merck
V114-031
Merck, unpublished		 Phase 3 RCT, full-term v. preterm infants PCV15
3+1 (2,4, 6, 12–15m)		 Australia, Canada, Finland, Germany, Israel, Malaysia, Peru, Taiwan, Thailand, US Full-term (>37 wks) and preterm infants (<37 wks); 42–90 days at enrollment 2398 1965 433 safety Merck

RCT = randomized controlled trial; PCV13 = 13-valent pneumococcal conjugate vaccine; PCV15 = 15-valent pneumococcal conjugate vaccine

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Content Source:
National Center for Immunization and Respiratory Diseases (NCIRD)