About
The Evidence to Recommendations (EtR) frameworks describe information considered in moving from evidence to ACIP vaccine recommendations.
Summary
Question: Should PCV20 without PPSV23 be recommended as an option for pneumococcal vaccination for U.S. children aged 2–18 years with underlying medical conditions that increase the risk of pneumococcal disease?
Population: U.S. children 2–18 years of age with underlying medical conditions*
*underlying medical conditions defined as cerebrospinal fluid leak; chronic renal failure or nephrotic syndrome; cochlear implant; 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; sickle cell disease and other hemoglobinopathies. For children aged 2–5 years, also includes chronic heart or lung disease, and diabetes mellitus.
Intervention: PCV20 without PPSV23
Comparison: PCV13 or PCV15 with PPSV23 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 2–18 years of age with underlying medical conditions*
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, use of either PCV13 or PCV15 and the 23-valent pneumococcal polysaccharide vaccine (PPSV23) was recommended for children aged 2–18 years with certain underlying medical conditions* (PPSV23 only was recommended for children aged 6–18 years with chronic heart or lung disease, or diabetes). 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 with certain underlying medical conditions as an option for pneumococcal vaccination.
Public Health Problem
References in this table:12345678
Criteria | Work Group Judgements | Evidence | Additional Information |
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Is the problem of public health importance? | Yes |
Acute Otitis Media (AOM)
Pneumonia
Invasive pneumococcal disease
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Benefits and Harms
Reference in this table:9
Criteria | Work Group Judgements | Evidence | Additional Information |
---|---|---|---|
How substantial are the desirable anticipated effects? | Moderate |
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How substantial are the undesirable anticipated effects? | Minimal |
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Do the desirable effects outweigh the undesirable effects? | Favors intervention, Favors both |
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What is the overall certainty of the evidence of effects? | Effectiveness of the intervention: Very low
Safety of intervention: Very low
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Values
Criteria | Work Group Judgements | Evidence | Additional Information |
---|---|---|---|
Does the target population feel that the desirable effects are large relative to undesirable effects? | Probably yes, Yes |
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The WG members’ interpretation was split between “Yes” and “Probably Yes”. The split in interpretation was due to the uncertainties about the desirable effects (added benefit) relative to undesirable effects (safety) from PCV20 use without PPSV23 use. |
Is there important uncertainty about or variability in how much people value the main outcomes? | Probably no important uncertainty or variability |
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While the majority of the WG members believed that there are no important uncertainty or variability, a minority believed that certain subpopulations, especially those who do not have regular access to healthcare providers, could probably have important uncertainty about the safety of vaccines. |
Acceptability
References in this table:101112
Criteria | Work Group Judgements | Evidence | Additional Information |
---|---|---|---|
Is the intervention acceptable to key stakehold-ers? | Probably yes, Yes | Findings from three web-based surveys among healthcare providers (HCP) who administer pneumococcal vaccines were reviewed.
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Resource use
References in this table: 1213141516
Criteria | Work Group Judgements | Evidence | Additional Information |
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Is the intervention a reasonable and efficient allocation of resources? | Yes |
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Equity
References in this table:1617181920212223
Criteria | Work Group Judgements | Evidence | Additional Information |
---|---|---|---|
What would be the impact of the intervention on health equity? | Probably increased | Disease Burden
Vaccination Coverage
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Feasibility
References in this table:212223
Criteria | Work Group Judgements | Evidence | Additional Information |
---|---|---|---|
Is the intervention feasible to implement? | Yes |
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Balance of consequences
Desirable consequences probably 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). In addition, no PCV20 clinical trial data are available for children with underlying medical conditions. Uncertainties also remain regarding a dose of PCV20 early in childhood would provide sufficient protection later in childhood for children who have underlying conditions who are currently recommended to receive PPSV23. At the same time, a recommendation of PCV20 without PPSV23 for children with underlying conditions could simplify the recommendations and storage and improve vaccine coverage.
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.
- Pelton SI, Weycker D, Farkouh RA, Strutton DR, Shea KM, Edelsberg J. Risk of pneumococcal disease in children with chronic medical conditions in the era of pneumococcal conjugate vaccine. Clin Infect Dis. 2014;59(5):615-23.
- 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. Safety and Immunogenicity Study of 20vPnC in Healthy Children 15 Months Through 17 Years of Age. New York, New York: Wyeth Pharmaceuticals LLC; 2020.
- 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 Findings. 2023.
- Stoecker C. Pneumococcal work group discussion. 2023.
- 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.
- 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.
- Woinarowicz M, Howell M. Comparing vaccination coverage of American Indian children with White children in North Dakota. Public Health. 2020;186:78-82.
- 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.
- Fu LY, Torres R, Caleb S, Cheng YI, Gennaro E, Thoburn E, et al. Vaccination coverage among young homeless children compared to US national immunization survey data. Vaccine. 2021;39(45):6637-43.
- 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.
- Reeves SL, Jary HK, Gondhi JP, Kleyn M, Wagner AL, Dombkowski KJ. Pneumococcal vaccination coverage among children with sickle cell anemia, sickle cell trait, and normal hemoglobin. Pediatr Blood Cancer. 2018;65(10):e27282.
- Mirza A, Jagadish A, Trimble K, Olanrewaju A. Improving Pneumococcal Vaccination Rates in an Inpatient Pediatric Diabetic Population. Ochsner J. 2022;22(3):239-43.
- Harris JG, Harris LA, Olarte L, Elson EC, Moran R, Blowey DL, et al. Improving Pneumococcal Vaccination Rates in High-risk Children in Specialty Clinics. Pediatrics. 2022;149(4).