About
The Evidence to Recommendations (EtR) frameworks describe information considered in moving from evidence to ACIP vaccine recommendations.
Summary
Question:
Should PCV20 be recommended as an option for pneumococcal conjugate vaccination according to currently recommended dosing and schedules, for U.S. children aged <2 years?
Population: U.S. children <2 years of age
Intervention: PCV20 according to currently recommended pneumococcal conjugate vaccination dosing and schedules
Comparison: PCV13 or PCV15 according to currently recommended dosing and schedules
Main Outcomes: Vaccine-type invasive pneumococcal disease; vaccine-type non-bacteremic pneumococcal pneumonia; vaccine-type acute otitis media; vaccine-type pneumococcal death; serious adverse events following immunization
Setting: U.S. children <2 years of age
Perspective: Clinical perspective
Background
On April 27, 2023, the FDA approved use of 20-valent pneumococcal conjugate vaccine (Pfizer [PCV20]) in children aged 6 weeks through 17 years. 15-valent pneumococcal conjugate vaccine (PCV15) use in children was approved and recommended by the ACIP in June 2022. Unlike the 13-valent pneumococcal conjugate vaccine (PCV13), which was first licensed for use in children, the new PCVs (PCV15, PCV20) were first licensed for use in adults in 2021.
Before the June 2023 ACIP meeting, either PCV13 or PCV15 was recommended for routine use in all infants aged <2 years as a 4-dose series at ages 2, 4, 6, and 12–15 months. Catch-up vaccination was recommended through age 59 months for healthy children, and through age 71 months for children with underlying medical conditions. The ACIP Pneumococcal Vaccines Work Group employed the Evidence to Recommendation (EtR) framework, using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach, to guide its deliberations regarding use of PCV20 in U.S. children as an option for pneumococcal conjugate vaccination.
Public Health Problem
References in this table:1234567
Criteria | Work Group Judgements | Evidence | Additional Information |
---|---|---|---|
Is the problem of public health importance? | Yes |
Acute Otitis Media (AOM)
Pneumonia
Invasive pneumococcal disease
|
|
Benefits and Harms
References in this table891011
*Noninferiority for difference in percentages of participants was defined as the lower bound of 2-sided 95% confidence interval for percent difference (PCV20-PCV13)>-10%. Additional 7 serotypes contained in PCV20 but not in PCV13 were compared with a PCV13 serotype with the lowest percentage excluding serotype 3.
†Measured as the proportion of participants meeting IgG threshold value of ≥ 0.35 µg/mL except for ≥0.23 µg/ml for serotype 5, ≥0.10 µg/ml for serotype 6B, and ≥0.23 µg/ml for serotype 19A. The direct-binding Luminex® immunoassay (dLIA) that was used to measure the IgG concentration was bridged to the WHO ELISA to establish dLIA specific threshold values for each vaccine serotype that correspond to the established ≥0.35 µg/mL WHO ELISA threshold value.
‡Noninferiority for GMC ratio was defined as the lower bound of 2-sided 95% confidence interval of IgG GMC ratio (PCV20/PCV13) >0.5. Additional 7 serotypes contained in PCV20 but not in PCV13 were compared with a PCV13 serotype with the lowest percentage excluding serotype 3.
Values
Reference in this table12
Criteria | Work Group Judgements | Evidence | Additional Information |
---|---|---|---|
Does the target population feel that the desirable effects are large relative to undesirable effects? | Probably yes |
|
Given lack of data assessing the public’s perception of PCV20, the Work Group believed that uncertainties remained regarding whether the target population feels that the desirable effects are large relative to undesirable effects. |
Is there important uncertainty about or variability in how much people value the main outcomes? | Possibly important uncertainty or variability, Probably no important uncertainty or variability |
|
Some Work Group members believed that there may be important uncertainty or variability given that there are no PCV20 efficacy data against disease outcomes and given that some express vaccine hesitancy. Others believed that given the increased incidence of pneumococcal disease during past fall/winter, most would likely value use of PCV20. A minority believed that there is no important uncertainty or variability, since there are no vaccine efficacy data. |
Acceptability
References in this table131415
Criteria | Work Group Judgements | Evidence | Additional Information |
---|---|---|---|
Is the intervention acceptable to key stakehold-ers? | Yes | Findings from three web-based surveys among healthcare providers (HCP) who administer pneumococcal vaccines were reviewed.
|
Resource Use
References in this table161718192021
Criteria | Work Group Judgements | Evidence | Additional Information |
---|---|---|---|
Is the intervention a reasonable and efficient allocation of resources? | Yes |
|
|
Equity
References in this table122223242526
Criteria | Work Group Judgements | Evidence | Additional Information |
---|---|---|---|
What would be the impact of the intervention on health equity? | Probably increased | Disease Burden
Vaccine Coverage
|
|
Feasibility
Reference in this table12
Criteria | Work Group Judgements | Evidence | Additional Information |
---|---|---|---|
Is the intervention feasible to implement? | Yes |
|
The work group believed that, adding PCV20 as an option for pneumococcal conjugate vaccination using the currently recommended dosing and schedule is expected to be feasible. |
Balance of consequences
Desirable consequences probably outweigh undesirable consequences in most settings
Desirable consequences clearly outweigh undesirable consequences in most settings
Additional Considerations
PCV20 has a favorable safety profile and is expected to protect against pneumococcal disease caused by additional serotypes that are contained in PCV20 but not in PCV13 or 15. However, since both PCV15 and PCV20 were licensed by safety and immunogenicity data only, uncertainties remain regarding the clinical implications of the immunogenicity study findings (specifically, numerically lower immunogenicity of PCV20 for the shared serotypes with PCV13 and numerically higher immunogenicity of PCV15 against serotype 3 compared with PCV13). The cost effectiveness of PCV20 use compared with current PCVs is largely dependent on indirect effects against adult disease and uncertainties remain in the price of vaccines. Thus, preferential use of PCV20 was not proposed by the Work Group. PCVs have been used in U.S. children for >20 years and have achieved high vaccine coverage, so use of PCV20 is likely to be acceptable and feasible.
View the complete list of EtR Frameworks
- Tong S, Amand C, Kieffer A, Kyaw MH. Trends in healthcare utilization and costs associated with acute otitis media in the United States during 2008-2014. BMC health services research. 2018;18(1):318.
- Lewnard JA, King LM, Fleming-Dutra KE, Link-Gelles R, Van Beneden CA. Incidence of Pharyngitis, Sinusitis, Acute Otitis Media, and Outpatient Antibiotic Prescribing Preventable by Vaccination Against Group A Streptococcus in the United States. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2021;73(1):e47-e58.
- Hu T, Done N, Petigara T, Mohanty S, Song Y, Liu Q, et al. Incidence of acute otitis media in children in the United States before and after the introduction of 7- and 13-valent pneumococcal conjugate vaccines during 1998-2018. BMC infectious diseases. 2022;22(1):294.
- Update: pneumococcal polysaccharide vaccine usage–United States. MMWR Morbidity and mortality weekly report. 1984;33(20):273-6, 81.
- Kaur R, Fuji N, Pichichero ME. Dynamic changes in otopathogens colonizing the nasopharynx and causing acute otitis media in children after 13-valent (PCV13) pneumococcal conjugate vaccination during 2015-2019. European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology. 2022;41(1):37-44.
- King L. February 2023 ACIP meeting presentation. Pediatric outpatient ARI visits and antibiotic use attributable to serotypes in higher valency PCVs. February 2023 ACIP meeting2023.
- Tong S, Amand C, Kieffer A, Kyaw MH. Trends in healthcare utilization and costs associated with pneumonia in the United States during 2008-2014. BMC health services research. 2018;18(1):715.
- Wyeth Pharmaceuticals LLC. 20-valent Pneumococcal Conjugate Vaccine Safety and Immunogenicity Study of a 4-Dose Series in Healthy Infants. New York, New York: Wyeth Pharmaceuticals LLC; 2020.
- Senders S, Klein NP, Lamberth E, Thompson A, Drozd J, Trammel J, et al. Safety and Immunogenicity of a 20-valent Pneumococcal Conjugate Vaccine in Healthy Infants in the United States. The Pediatric infectious disease journal. 2021;40(10):944-51.
- Wyeth Pharmaceuticals LLC. 20-valent Pneumococcal Conjugate Vaccine Safety Study in Healthy Infants. New York, New York: Wyeth Pharmaceuticals LLC; 2020.
- Centers for Disease Control & Prevention. GRADE: 15-valent pneumococcal conjugate vaccine (PCV15) use in children aged <2 years 2022 [updated August 31, 2022. Available from: https://wcms-wp.cdc.gov/acip/grade-evidence-tables-recommendations-in-mmwr/grading-recommendations-pcv15-children-2-years.html.
- Hill HA, Chen M, Elam-Evans LD, Yankey D, Singleton JA. Vaccination Coverage by Age 24 Months Among Children Born During 2018-2019 – National Immunization Survey-Child, United States, 2019-2021. MMWR Morbidity and mortality weekly report. 2023;72(2):33-8.
- OPEN Health. Provider Knowledge, Attitude, and Preferences Towards Pediatric Pneumococcal Vaccines. 2023.
- Merck & Co. Inc. HCP Preferences Concerning Pediatric Pneumococcal Vaccines Report. 2023.
- Myers K, Pierce N, Poulos C, Arguedas A, Chilson E, Hauber B, et al. US Health Care Providers’ Preferences for Pediatric Pneumococcal Conjugate Vaccines. Preliminary Finding
- Stoecker C, Kobayashi M, Matanock A, Cho B-H, Pilishvili T. Cost-effectiveness of continuing pneumococcal conjugate vaccination at age 65 in the context of indirect effects from the childhood immunization program. Vaccine. 2020;38(7):1770-7.
- Tong S, Amand C, Kieffer A, Kyaw MH. Trends in healthcare utilization and costs associated with pneumonia in the United States during 2008–2014. BMC Health Services Research. 2018;18(1):1-8.
- Tong S, Amand C, Kieffer A, Kyaw MH. Trends in healthcare utilization and costs associated with acute otitis media in the United States during 2008–2014. BMC health services research. 2018;18(1):1-10.
- Stoecker C, Hampton LM, Link-Gelles R, Messonnier ML, Zhou F, Moore MR. Cost-effectiveness of using 2 vs 3 primary doses of 13-valent pneumococcal conjugate vaccine. Pediatrics. 2013;132(2):e324-e32.
- Andrews NJ, Waight PA, Burbidge P, Pearce E, Roalfe L, Zancolli M, et al. Serotype-specific effectiveness and correlates of protection for the 13-valent pneumococcal conjugate vaccine: a postlicensure indirect cohort study. The Lancet infectious diseases. 2014;14(9):839-46.
- CDC. Pneumococcal vaccines (ACIP Presentation Slides) 2023 [cited 2023 March 2023]. Available from: https://wcms-wp.cdc.gov/acip/acip-meetings/acip-presentation-slides-february-22-24-2023-meeting.html
- Kobayashi M. February 2023 ACIP meeting presentation. Evidence to Recommendations Framework (Preliminary): Use of 20-valent Pneumococcal Conjugate Vaccine in U.S. Children. February 2023 ACIP meeting2023.
- Littlepage SJ, Sutcliffe CG, Simons-Petrusa B, Harker-Jones M, Weatherholtz RC, Roessler K, et al. Impact of PCV13 on Invasive Pneumococcal Disease among Native Americans Less than 5 Years of Age Living on Navajo Nation. 9th International Meeting on Indigenous Child Health; September 10 and 11, 2021; Virtual2021.
- Nickel AJ, Puumala SE, Kharbanda AB. Vaccine-preventable, hospitalizations among American Indian/Alaska Native children using the 2012 Kid’s Inpatient Database. Vaccine. 2018;36(7):945-8.
- Woinarowicz M, Howell M. Comparing vaccination coverage of American Indian children with White children in North Dakota. Public Health. 2020;186:78-82.
- Centers for Disease Control and Prevention. ChildVaxView [updated September 28, 2020. Available from: https://www.cdc.gov/vaccines/imz-managers/coverage/childvaxview/interactive-reports/index.html.