About
The Evidence to Recommendations (EtR) frameworks describe information considered in moving from evidence to ACIP vaccine recommendations.
Summary
Question: Should PCV15 be recommended for U.S. children with underlying medical conditions 2–18 years of age as an option for pneumococcal conjugate vaccination according to currently recommended dosing and schedules?
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: PCV15 according to currently recommended pneumococcal conjugate vaccination dosing and schedules
Comparison: PCV13 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
In June 2022, the Food and Drug Administration approved an expanded usage of 15-valent pneumococcal conjugate vaccine (PCV15 [Merck Sharp & Dohme LLC]) to include children. PCV15 was licensed for use in adults in 2021.
Currently, use of both PCV13 and the 23-valent pneumococcal polysaccharide vaccine (PPSV23) is recommended for children aged 2–18 years with certain 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 PCV15 in U.S. children with certain underlying medical conditions as an option for pneumococcal conjugate vaccination.
Problem
References in this section:1234
Criteria | Judgement | Research Evidence | Additional Considerations |
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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
Criteria | Judgement | Research Evidence | Additional Considerations |
---|---|---|---|
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 both | In comparing PCV15 with PCV13 for use in children aged 2–18 years with underlying conditions, the Work Group felt that both interventions are favorable. | |
What is the overall certainty of this evidence for the critical outcomes? | Effectiveness of the intervention: Low
Safety of the intervention: Low
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For critical outcomes, the certainty of evidence was low for effectiveness and low for safety of the intervention. Certainty of evidence for effectiveness was downgraded for indirectness (immunogenicity studies only, no clinical efficacy data), and imprecision (small sample size of the studies). Certainty of evidence for safety was downgraded twice for imprecision (very small sample size of the studies and no vaccine-related serious adverse events reported in either study arm). |
Values
Reference in this section:7
Criteria | Judgement | Research Evidence | Additional Considerations |
---|---|---|---|
Does the target population feel the desirable effects are large relative to the undesirable effects? | Probably 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 added benefit from PCV15 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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Acceptability
Reference in this section:8
Criteria | Judgement | Research Evidence | Additional Considerations |
---|---|---|---|
Is the intervention acceptable to key stakeholders? | Probably yes |
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Resource Use
Reference in this section:9
Criteria | Judgement | Research Evidence | Additional Considerations |
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Is the intervention a reasonable and efficient allocation of resources? | Probably yes |
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Equity
References in this section:1011121314
Criteria | Judgement | Research Evidence | Additional Considerations |
---|---|---|---|
What would be the impact on health equity? | Probably no impact | Disease Burden
Vaccination Coverage
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Feasibility
Criteria | Judgement | Research Evidence | Additional Considerations |
---|---|---|---|
Is the intervention feasible to implement? | Probably yes |
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- 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.
- 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.
- 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.
- Merck Sharp, Dohme Corp. A Study to Evaluate the Safety, Tolerability, and Immunogenicity of V114 in Children With Sickle Cell Disease (V114-023/PNEU-SICKLE) 2020 [updated June 8. Available from: https://ClinicalTrials.gov/show/NCT03731182.
- Merck Sharp, Dohme Corp. Safety and Immunogenicity of V114 in Children Infected With Human Immunodeficiency Virus (HIV) (V114-030/PNEU-WAY PED) 2021 [updated May 3. Available from: https://ClinicalTrials.gov/show/NCT03921424.
- Hill HA, Yankey D, Elam-Evans LD, Singleton JA, Sterrett N. Vaccination Coverage by Age 24 Months Among Children Born in 2017 and 2018 – National Immunization Survey-Child, United States, 2018-2020. MMWR Morb Mortal Wkly Rep. 2021;70(41):1435-40.
- Merck & Co. Inc. Healthcare Provider Preferences Related to Multi-Valent Pneumococcal Conjugate Vaccines. 2022.
- Centers for Disease Control and Prevention. CDC Vaccine Price List 2022 [Available from: www.cdc.gov/vaccines/programs/vfc/awardees/vaccine-management/price-list/index.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.
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- Centers for Disease Control and Prevention. ChildVaxView [updated September 28, 2020. Available from: www.cdc.gov/vaccines/imz-managers/coverage/childvaxview/interactive-reports/index.html.