National Center for Immunization & Respiratory Diseases 

Evidence to Recommendation Framework: 

Use of 15-valent and 20-valent Pneumococcal 

Conjugate Vaccines in Adults 

Miwako Kobayashi, MD, MPH 

ACIP meeting 

June 25, 2021 
 

 

 

Evidence to Recommendation (EtR) framework 

 To provide structure for describing information considered in moving from 

evidence to ACIP vaccine recommendations. 

 To provide transparency on the impact of additional factors on 

deliberations when considering recommendations. 
Evidence to Recommendations (EtR) Framework 

EtRDomain Question 

Public Health Problem • Is the problem of public health importance? 

Benefits and Harms • How substantial are the desirable anticipated effects? 

• How substantial are the undesirable anticipated effects? 

• Do the desirable effects outweigh the undesirable effects? 

Values • Does the target population feel the desirable effects are large 

relative to the undesirable effects? 

• Is there important variability in how patients value the outcomes? 

Acceptability • Is the intervention acceptable to key stakeholders? 

Feasibility • Is the intervention feasible to implement? 

Resource Use • Is the intervention a reasonable and efficient allocation of 

resources? 

Equity • What would be the impact of the intervention on health equity? 
Evidence to Recommendations (EtR) Framework 

EtRDomain Question 

Public Health Problem Is theproblem of public health importance? 

Benefits and Harms How substantial are the desirable anticipated effects? 

 How substantial are the undesirable anticipated effects? 

 Do the desirable effects outweigh the undesirable effects? 

Values Does the target population feel the desirable effects are large 

elative to the undesirable effects? 

 Is there important variability in how patients value the outcomes?

Acceptability Is theintervention acceptable to key stakeholders? 

Feasibility Is theintervention feasible to implement? 

Resource Use Is theintervention a reasonable and efficient allocation of 

esources? 

Equity What would be the impact of theintervention on health equity? 

•

•

•

•

•

r

•

•

•

•

r

•

Problem=pneumococcal disease, Intervention=PCV15 or PCV20 use 
19–64 years ≥65 years

None of the conditions listed below No recommendation PCV13* based on shared 

clinical decision making, 

PPSV23 for all 

Chronic medical conditions† (CMC) PPSV23 PCV13* based on shared 

clinical decision making, 

PPSV23 for all 

Cochlear implant, CSF leak 

Immunocompromising conditions 

Both PCV13* and PPSV23 

Both PCV13* and PPSV23, 

repeat PPSV23 after 5 years 

Both PCV13* and PPSV23 

Both PCV13* and PPSV23 

 

Current ACIP Pneumococcal Vaccine Recommendations by Age and Risk Groups 

PCV13: 13-valent pneumococcal conjugate vaccine 

PPSV23: 23-valent pneumococcal polysaccharide vaccine 

*If not previously given; †Examples include alcoholism, chronic heart/liver/lung disease, diabetes, cigarette smoking 

https://www.cdc.gov/vaccines/vpd/pneumo/downloads/pneumo-vaccine-timing.pdf 
 

 

 

 

19–64 years ≥65 years

None of the conditions listed below No recommendation PCV13* based on shared 

clinical decision making, 

PPSV23 for all 

Chronic medical conditions† (CMC) PPSV23 PCV13* based on shared 

clinical decision making, 

PPSV23 for all 

Cochlear implant, CSF leak Both PCV13* and PPSV23 Both PCV13* and PPSV23 

Immunocompromising conditions Both PCV13* and PPSV23, Both PCV13* and PPSV23 

repeat PPSV23 after 5 years Immunocompromised adults 

 

Current ACIP Pneumococcal Vaccine Recommendations by Age and Risk Groups 

PCV13: 13-valent pneumococcal conjugate vaccine 

PPSV23: 23-valent pneumococcal polysaccharide vaccine 

*If not previously given; †Examples include alcoholism, chronic heart/liver/lung disease, diabetes, cigarette smoking 

https://www.cdc.gov/vaccines/vpd/pneumo/downloads/pneumo-vaccine-timing.pdf 
 

 

 

 

 

Current ACIP Pneumococcal Vaccine Recommendations by Age and Risk Groups 

19–64 years ≥65 years

None of the conditions listed below No recommendation PCV13* based on shared 

clinical decision making, 

PPSV23 for all 

Chronic medical conditions† (CMC) PPSV23 PCV13* based on shared 

clinical decision making, 

PPSV23 for all 

Cochlear implant, CSF leak Both PCV13* and PPSV23 Both PCV13* and PPSV23 

Immunocompetent adults 

Immunocompromising conditions Both PCV13* and PPSV23, Both PCV13* and PPSV23 

repeat PPSV23 after 5 years 

PCV13: 13-valent pneumococcal conjugate vaccine 

PPSV23: 23-valent pneumococcal polysaccharide vaccine 

*If not previously given; †Examples include alcoholism, chronic heart/liver/lung disease, diabetes, cigarette smoking 

https://www.cdc.gov/vaccines/vpd/pneumo/downloads/pneumo-vaccine-timing.pdf 
 

 

 

 

 

Current ACIP Pneumococcal Vaccine Recommendations by Age and Risk Groups 

19–64 years ≥65 years

None of the conditions listed below No recommendation PCV13* based on shared 

clinical decision making, 

PPSV23 for all 

Chronic medical conditions† (CMC) PPSV23 PCV13* based on shared 

clinical decision making, 

PPSV23 for all 

Cochlear implant, CSF leak Both PCV13* and PPSV23 Both PCV13* and PPSV23 

Adults with CMC 

Immunocompromising conditions Both PCV13* and PPSV23, Both PCV13* and PPSV23 

repeat PPSV23 after 5 years 

PCV13: 13-valent pneumococcal conjugate vaccine 

PPSV23: 23-valent pneumococcal polysaccharide vaccine 

*If not previously given; †Examples include alcoholism, chronic heart/liver/lung disease, diabetes, cigarette smoking 

https://www.cdc.gov/vaccines/vpd/pneumo/downloads/pneumo-vaccine-timing.pdf 
 

 

 

 

 

 

 

 

 

 

Questions 1. Should PCV15 be routinely recommended to US adults ≥65 

years? 

2. Should PCV15 be routinely recommended to US adults ≥65 

years in series with PPSV23? 

Population US adults aged ≥65 years

Intervention 1. One dose of PCV15 

2. One dose of PCV15 followed by PPSV23 

Comparison • PCV13 followed by PPSV23 (immunocompromised adults*) 

• PPSV23** (immunocompetent adults*) 

Outcomes VT-IPD, VT-NBPP, deaths, serious adverse events 

VT: vaccine-type, IPD: invasive pneumococcal disease, NBPP: non-bacteremic pneumococcal pneumonia 

*immunocompromised adults include adults with immunocompromising condition (chronic renal failure, nephrotic syndrome, 

immunodeficiency, iatrogenic immunosuppression, generalized malignancy, human immunodeficiency virus, Hodgkin disease, leukemia, 

lymphoma, multiple myeloma, solid organ transplants, congenital or acquired asplenia, sickle cell disease, or other hemoglobinopathies), CSF 

leak, or cochlear implant; immunocompetent adults are those without these conditions. 

**PCV13 recommended based on shared clinical decision making for immunocompetent adults ≥65 years
 

 

 

 

 

 

Questions Should PCV20 be routinely recommended to US adults... 

≥50 years? ≥65 years?

Population US adults aged ≥50 years US adults aged ≥65 years 

Intervention One dose of PCV20 

Comparison PCV13 followed by PPSV23 (immunocompromised*) 

PPSV23 only (immunocompetent* adults aged ≥65 years**)

PPSV23 only (50–64yrs, CMC†) NA 

No vaccination (50–64yrs, no 

indications ) 

NA 

Outcomes VT-IPD, VT-NBPP, deaths, serious adverse events 

CMC: chronic medical conditions, VT: vaccine-type, IPD: invasive pneumococcal disease, NBPP: non-bacteremic pneumococcal pneumonia 

*immunocompromised adults include adults with immunocompromising condition (chronic renal failure, nephrotic syndrome, immunodeficiency, iatrogenic immunosuppression, generalized 

malignancy, human immunodeficiency virus, Hodgkin disease, leukemia, lymphoma, multiple myeloma, solid organ transplants, congenital or acquired asplenia, sickle cell disease, or other 

hemoglobinopathies), CSF leak, or cochlear implant; immunocompetent adults are those without these conditions. 

†CMC includes chronic heart/lung/liver disease, cirrhosis, diabetes mellitus, alcoholism, and cigarette smoking 

**PCV13 recommended based on shared clinical decision making for immunocompetent adults ≥65 years
Public Health Problem 

Is pneumococcal disease of public health importance? 
 

Increasing

burden 

ia 

Pneumococcal disease

 Invasive pneumococcal 

disease (IPD) 

e.g., meningitis, bacteremia, 

bacteremic pneumonia 

 Non-invasive disease 

e.g., non-bacteremic pneumon

Bacteremia 

Pneumonia 

Otitis media/sinusitis 

Meningitis 

IPD 
 

Estimated burden of pneumococcal disease in U.S. 

adults aged ≥19 years

 In 2018, ~30,000 IPD cases and ~3,500 IPD deaths occurred1 

 In 2017, ~103,000 hospitalized pneumococcal pneumonia cases 

occurred2 

– ~40 to 55% of the burden in adults aged ≥65 years

– ~80% of the burden in adults aged ≥50 years

1. CDC ABCs, 2018, 2. CDC SNiPP, 2017 
 

 

 

Impact of Pneumococcal Conjugate Vaccine (PCV) Use in the United

States to date 

• Introduction of PCV in children reduced vaccine-preventable 

pneumococcal disease burden in adults 

• Includes adults at increased risk of pneumococcal disease 

• Population level impact after PCV13 was recommended for all adults 

aged ≥65 years in 2014:

• Reductions in PCV13-type pneumococcal pneumonia incidence documented 

• No impact on PCV13-type invasive pneumococcal disease (IPD) observed 

• Most common remaining PCV13-type disease is due to serotype 3 
IPD Incidence by Serotype Group and Age Group, ABCs 

2018–2019 

25 

20 

15 

10 

5 

0 

Age group (years) 

PCV13+6C PCV15 non-PCV13 PCV20 non-PCV15 PPV23 non-PCV20 NVT 

IPD incidence per 100,000 pop 

50-64 65+ 
IPD Incidence by Serotype Group and Age Group, ABCs 

2018–2019 

25 

20 

15 

10 

5 

0 

Age group (years) 

PCV13+6C PCV15 non-PCV13 PCV20 non-PCV15 PPV23 non-PCV20 NVT 

IPD incidence per 100,000 pop 

PCV15/non-PCV13 

type ~15% 

50-64 65+ 
IPD Incidence by Serotype Group and Age Group, ABCs 

2018–2019 

25 

20 

15 

10 

5 

0 

Age group (years) 

PCV13+6C PCV15 non-PCV13 PCV20 non-PCV15 PPV23 non-PCV20 NVT 

IPD incidence per 100,000 pop 

PCV20/non-PCV13 

type ~30% 

50-64 65+ 
 

Public Health Problem 

Is pneumococcal disease of public health importance in adults 

aged ≥50 years? 

□ No 

□ Probably no 

□ Probably yes 

□ Yes 

□ Varies 

□ Don’t know 
 

 

Benefits and Harms 

How substantial are the desirable anticipated effects? 

- How substantial is the anticipated effect for: 

Vaccine-type IPD 

Vaccine-type non-bacteremic pneumococcal pneumonia 

Vaccine-type death? 
 

 

Benefits and Harms 

How substantial are the undesirable anticipated effects? 

- How substantial is the anticipated effect for serious adverse events? 
 

 

Benefits and Harms 

Do the desirable effects outweigh the undesirable effects? 

- What is the balance between the desirable effects relative to the 

undesirable effects? 
Serotypes Contained in Pneumococcal Vaccines 

1 3 4 5 6A 6B 7 F 9V 14 18 

C 

19 

A 

19 

F 

23 

F 

22 

F 

33 

F 

8 10 

A 

11 

A 

12 

F 

15 

B 

2 9N 17 

F 

20 

PCV13 

PCV15 

PPSV23 

Shared serotypes: 

• PCV15 vs. PCV13=13 serotypes 

• PCV15 vs. PPSV23=14 serotypes
 

 

 

 

 

 

 

 

Summary of Available Evidence from PCV15 studies: Benefits 

 PCV15 vs. PCV13: 

– GMTs and % seroresponders higher for PCV15 recipients for some 

serotypes shared with PCV13 

– In one phase 3 RCT, PCV15 met non-inferiority criteria for 13/13 

serotypes based on GMT ratio; serotype 3 response met the 

superiority criteria. 

Moderate certainty of evidence 

 PCV15 vs. PPSV23: In one phase 2 RCT, PCV15 met non-inferiority criteria 

for 14/14 serotypes based on GMT ratios

Moderate certainty of evidence 

Please see GRADE summary tables for details 
 

 

Benefits and Harms 

How substantial are the desirable anticipated effects? 

 PCV15 use for persons aged ≥65 years

□ Minimal 

□ Small 

□ Moderate 

□ Large 

□ Varies 

□ Don’t know 
 

 

Benefits and Harms 

How substantial are the desirable anticipated effects? 

 PCV15 use for persons aged ≥65 years

□ Minimal 

□ Small 

□ Moderate 

□ Large 

□ Varies 

□ Don’t know 

• PCV15 contains 2 additional serotypes vs. PCV13 

• No PPSV23 lose coverage for 9 serotypes 

• Recommendation with a single vaccine may achieve 

higher vaccine coverage 
 

 

 

Summary of Available Evidence, PCV15-PPSV23 series 

 PCV15-PPSV23 vs. PCV13-PPSV23 immunogenicity: 

– In three phase 3 RCTs, GMTs and % seroresponders were higher in 

PCV15-PPSV23 recipients for some shared serotypes 

Moderate certainty of evidence 

Please see GRADE summary tables for details 
Benefits and Harms 

How substantial are the desirable anticipated effects? 

 PCV15 use for persons aged ≥65 years in series with PPSV23

• PCV15 contains 2 additional serotypes vs. PCV13 

 

 

 

□ Minimal 

□ Small 

□ Moderate 

□ Large 

□ Varies 

□ Don’t know 
 

 

 

 

 

 

Summary of Available Evidence from PCV15 studies: Harms 

 PCV15 vs. PCV13, PPSV23 Serious Adverse Events (SAEs): 

– No SAEs were associated with the vaccines 

Moderate certainty of evidence 

 PCV15-PPSV23 vs. PCV13-PPSV23 SAEs: 

– No SAEs were associated with the vaccines 

Moderate certainty of evidence 

Please see GRADE summary tables for details 
 

 

Benefits and Harms 

How substantial are the undesirable anticipated effects? 

□ Minimal 

□ Small 

□ Moderate 

□ Large 

□ Varies 

□ Don’t know 

 PCV15 use for persons aged≥65 years

 PCV15 use for persons aged ≥65 years in series 

with PPSV23 
 

 

 

Benefits and Harms 

Do the desirable effects outweigh the undesirable effects? 

- What is the balance between the desirable effects relative to the 

undesirable effects? 

□ Favors intervention* 

□ Favors current recommendation 

□ Favors both 

□ Favors neither 

□ Varies 

□ Don’t know 

*Intervention: 

 PCV15 use for persons aged≥65 years

 PCV15 use for persons aged ≥65 years

in series with PPSV23 
Serotypes Contained in Pneumococcal Vaccines 

1 3 4 5 6A 6B 7 F 9V 14 18 

C 

19 

A 

19 

F 

23 

F 

22 

F 

33 

F 

8 10 

A 

11 

A 

12 

F 

15 

B 

2 9N 17 

F 

20 

PCV13 

PCV20 

PPSV23 

Shared serotypes: 

• PCV20 vs. PCV13=13 serotypes 

• PCV20 vs. PPSV23=7 serotypes not included in PCV13 
 

 

 

 

 

 

 

 

 

 

Summary of Available Evidence from PCV20 studies: Benefits 

 PCV20 vs. PCV13: 

– In one phase 2 RCT, GMT and % seroresponders in PCV20 recipients 

lower for some shared serotypes. 

– In one phase 3 RCT, PCV20 met noninferiority criteria for all 13/13 

shared serotypes by GMT ratio. Moderate certainty of evidence 

 PCV20 vs. PPSV23: 

– In one phase 2 RCT, GMT and % seroresponders in PCV20 recipients 

higher for some shared serotypes. 

– In one phase 3 RCT, PCV20 met noninferiority criteria for 6/7 shared

serotypes (not met for serotype 8) based on GMT ratio; higher 

%seroresponders in 6/7 serotypes. Moderate certainty of evidence 

Please see GRADE summary tables for details 
 

 

 

Summary of Available Evidence from PCV20 studies: Benefits 

 Age 50–59 years vs. 60–64 years: 

– Noninferiority criteria met for all 20 serotypes in phase 3 RCT. 

Please see GRADE summary tables for details 
 

 

 

 

Benefits and Harms 

How substantial are the desirable anticipated effects? 

 PCV20 use for persons aged ≥50 years

□ Minimal 

□ Small 

□ Moderate 

□ Large 

□ Varies 

□ Don’t know 

 Some concerns about lower immunogenicity 

observed in PCV20 vs. PCV13 

 Noninferiority criteria largely met 

 Recommendation with single vaccine likely to 

improve vaccine coverage 

 Improved vaccine coverage in 50–64-year-olds 
 

 

 

 

Benefits and Harms 

How substantial are the desirable anticipated effects? 

 PCV20 use for persons aged ≥65 years

□ Minimal 

□ Small 

□ Moderate 

□ Large 

□ Varies 

□ Don’t know 

 Public health impact from the cost-effectiveness 

analysis deemed to be large 

 Some concerns about lower immunogenicity 

observed in PCV20 vs. PCV13 

 Additional impact from this age-based 

recommendation alone may not be large 
 

 

 

 

Summary of Available Evidence from PCV20 studies: Harms 

 PCV20 vs. PCV13 

– No vaccine-related SAEs reported. 

 PCV20-saline vs. PCV13-PPSV23 Moderate certainty of evidence 

– No vaccine-related SAEs reported. 

Moderate certainty of evidence 

Please see GRADE summary tables for details 
 

 

Benefits and Harms 

How substantial are the undesirable anticipated effects? 

□ Minimal 

□ Small 

□ Moderate 

□ Large 

□ Varies 

□ Don’t know 

 PCV20 use for persons aged≥50 years

 PCV20 use for persons aged ≥65 years
 

 

 

Benefits and Harms 

Do the desirable effects outweigh the undesirable effects? 

- What is the balance between the desirable effects relative to the 

undesirable effects? 

□ Favors intervention* 

□ Favors current recommendation 

□ Favors both 

□ Favors neither 

□ Varies 

□ Don’t know 

*Intervention: 

 PCV20 use for persons aged≥50 years

 PCV20 use for persons aged ≥65 years
 

 

 

 

Work Group Interpretation: Benefits and Harms 

EtR Domains 

Public Health 

Problem 

PCV15, ≥65 years PCV15 +PPSV23, PCV20, ≥50 years

≥65 years

Yes 

PCV20, ≥65 years

Benefits and Harms 

a. Benefits 

b. Harms 

Small Small 

Minimal 

Large Moderate-Large 

c. Benefit>Harm? Favors intervention 

d. Overall certainty: 

effectiveness 

Moderate 

e. Overall certainty: 

safety 

Moderate 

Note: Each policy question is compared to the current vaccine recommendation 
 

 

 

 

Work Group Interpretation: Benefits and Harms 

EtR Domains PCV15, ≥65 years PCV15 +PPSV23, 

≥65 years

PCV20, ≥50 years PCV20, ≥65 years

Public Health 

Problem 

Yes 

Benefits and Harms 

a. Benefits Small Small Large Moderate-Large 

b. Harms Minimal 

c. Benefit>Harm? Favors intervention 

d. Overall certainty: 

effectiveness 

Moderate 

e. Overall certainty: 

safety 

Moderate 

Note: Each policy question is compared to the current vaccine recommendation 
 

 

Values and Preferences 

Criterion 1: Does the target population feel that the desirable 

effects are large relative to undesirable effects? 

Criterion 2: Is there important uncertainty about, or variability 

in, how much people value the main outcomes? 
 

 

 

 

 

 

Values: Characteristics of Included Studies 

Study Study 

period 

Methods Population 

Albright 2017 2015 12 focus group 

discussions 

Adult patients of a safety net system including 8 

FQHCs in Denver metropolitan area (N=68, 78% 

White, 66% Hispanic ) 

Lu 2017 2017 Internet panel 

survey 

Nationally representative sample of U.S. adults 

aged ≥19 years (N=2,683)

Brown 2017* 2012 Mixed-method 

telephone 

survey 

Northwestern Medical Faculty Foundation General 

Internal Medicine Clinic, Black patients aged ≥65 

years with a documented refusal of PPSV23 (N=40)

Kaljee 2017* 2013-2014 8 focus group 

discussions 

Patients aged ≥65 years, patients at primary care

clinics that are part of the Henry Ford Health System 

(N=48, 92.9% female, 100% Black) 

*Included in 2019 EtR; FQHC= Federally Qualified Health Center 
 

 

 

 

Key Findings and Limitations 

 Awareness of pneumococcal vaccines lower compared to influenza 

vaccines, and may be variable by age or race/ethnicity 

 Awareness of pneumonia* high, but perceived susceptibility may be low 

 None were on PCV15 or PCV20 

 Findings may not be generalizable to the US population 

*used as an example of disease that the vaccine prevents 
 

 

 

 

 

Values and Preferences 

Criterion 1: Do adults feel that the desirable effects from 

vaccination are large relative to undesirable effects? 

□ No 

□ Probably no 

□ Probably yes 

□ Yes 

□ Varies 

□ Don’t know 

 PCV15 use for persons aged ≥65 years

 PCV15 use for persons aged ≥65 years in series 

with PPSV23 

 PCV20 use for persons aged ≥50 years

 PCV20 use for persons aged ≥65 years
 

 

Values and Preferences 

Criterion 1: Do adults feel that the desirable effects from 

vaccination are large relative to undesirable effects? 

□ No 

□ Probably no 

□ Probably yes 

□ Yes 

□ Varies 

□ Don’t know 

• Pneumococcal vaccines have been available 

and have achieved moderate coverage 

• Pneumococcal disease can result in serious 

consequences 
 

 

Values and Preferences 

Criterion 2: Is there important uncertainty about, or variability 

in, how much adults value the main outcomes? 

□ Important uncertainty or variability 

□ Probably important uncertainty or variability 

□ Probably not important uncertainty or variability 

□ No important uncertainty or variability 

□ No known undesirable outcomes 
 

Work Group Interpretation: Values and Preferences 

EtR Domains PCV15, ≥65 years PCV15 +PPSV23, 

≥65 years

PCV20, ≥50 years PCV20, ≥65 years

Public Health Problem Yes 

Benefits and Harms 

a. Benefits Small Small Large Moderate-Large 

b. Harms Minimal 

c. Benefit>Harm? Favors intervention 

d. Overall certainty: 

effectiveness 

e. Overall certainty: safety 

Moderate 

High 

Values 

a. Desirable 

>Undesirable? 

b. Uncertainty? 

Probably yes 

Probably not important uncertainty or variability 

Note: Each policy question is compared to the current vaccine recommendation 
Acceptability 

Is the option acceptable to key stakeholders? 
 

 

 

 

 

 

 

 

Acceptability: Review of Available Evidence 

 Healthcare Provider (HCP) Surveys 

– Vaccine Policy Collaborative Initiative (VPCI) Survey on PCV13 shared 

clinical decision-making (SCDM) recommendation (internet and mail)1 

• Primary care internists and family practice physicians 

– Pfizer’s survey on HCP preferences web-based survey2 

• Primary care physicians, physician assistants, nurse practitioners, 

pharmacists 

• Asked to rank hypothetical vaccine recommendations for adults aged ≥65

years and adults 19–64 years with underlying conditions

1. Hurley et al. 2021; 2. Pfizer HCP preference survey 2021 
 

 

 

Acceptability: Review of Available Evidence 

 Association of Immunization Managers (AIM) web-based survey 

• Primarily immunization program managers/directors 

• Option to provide narrative responses 
 

 

 

 

 

Key Findings 

 Confusion about current shared clinical decision-making for PCV13 use1,2 

 Preference for a simplified pneumococcal vaccine recommendation2,3 

– Same recommendation across age- and risk-groups3 

 Mixed responses on use of PCV in series with PPSV23 

– Routine PCV-PPSV23 use was the most preferred among provided 

options in one survey3 

– Implementation/communication challenges, health equity issues (in 

hard-to-reach population) expressed in another2 

1. Hurley et al. 2021; 2. AIM survey 2021; 3. Pfizer HCP preference survey 2021 
 

 

 

 

 

Key Findings 

 Mixed responses on lowering age-based recommendation 

– Respondents supportive of lowering the age-based recommendation 

in one survey3 

– Communication challenges, concerns for lower coverage in adults 50– 

64 yrs (less likely to seek primary health care) and potential for 

disparity by insurance status expressed in another2 

1. Hurley et al. 2021; 2. AIM survey 2021; 3. Pfizer HCP preference survey 2021 
 

Acceptability 

Is recommending PCV15 for persons aged ≥65 years acceptable 

to key stakeholders? 

□ No 

□ Probably no 

□ Probably yes 

□ Yes 

□ Varies 

□ Don’t know 
 

Acceptability 

Is recommending PCV15 for persons aged ≥65 years in series

with PPSV23 acceptable to key stakeholders? 

□ No 

□ Probably no 

□ Probably yes 

□ Yes 

□ Varies 

□ Don’t know 
 

 

Acceptability 

Is recommending PCV15 for persons aged ≥65 years in series

with PPSV23 acceptable to key stakeholders? 

□ No 

□ Probably no 

□ Probably yes 

□ Yes 

□ Varies 

□ Don’t know 

• PCV has been recommended in series with 

PPSV23 

• Logistical challenges associated with use of 2 

different vaccines in series 
 

 

 

 

 

 

Acceptability 

Is recommending PCV20 for persons aged ≥50 years acceptable 

to key stakeholders? 

□ No 

□ Probably no 

□ Probably yes 

□ Yes 

□ Varies 

□ Don’t know 

• Changing the target age may cause some initial 

implementation challenges 

• May provide an opportunity to improve coverage in 

adults aged <65 years with underlying conditions

• Recommendation consisting of one vaccine is likely 

more acceptable than the current recommendation 
 

Acceptability 

Is recommending PCV20 for persons aged ≥65 years acceptable 

to key stakeholders? 

□ No 

□ Probably no 

□ Probably yes 

□ Yes 

□ Varies 

□ Don’t know 
 

 

Work Group Interpretation: Acceptability 

EtR Domains PCV15, ≥65 years PCV15 +PPSV23, PCV20, ≥50 years PCV20, ≥65 years

≥65 years

Public Health Problem Yes 

Benefits and Harms 

a. Benefits Small Small Large Moderate-Large 

b. Harms Minimal 

c. Benefit>Harm? Favors intervention 

d. Overall certainty: Moderate 

effectiveness 

e. Overall certainty: safety High 

Values 

a. Desirable>Undesirable? Probably yes 

b. Uncertainty? Probably not important uncertainty or variability 

Acceptability Probably yes Varies Probably yes Yes 

Note: Each policy question is compared to the current vaccine recommendation 
 

Resource Use 

Is the option a reasonable and efficient allocation of resources? 
 

 

 

Cost-Effectiveness Analysis on PCV15 Policy Questions 

19–64 years with CMC and 

immunocompromising conditions 

All ≥65 years

Option 1 

“PCV15, ≥65 years”

PCV15 PCV15 

Option 2 

“PCV15 + PPSV23, ≥65 years”

PCV15+PPSV23 PCV15+PPSV23 
 

 

Cost-Effectiveness Analysis on PCV20 Policy Questions 

19–49 years with CMC and 

immunocompromising conditions 

All ≥50 years

Option 1 

“PCV20, ≥50 years”

PCV20 PCV20 

19–64 years with CMC and 

immunocompromising conditions 

All ≥65 years

Option 2 

“PCV20, ≥65 years”

PCV20 PCV20 

• Options compared to current pneumococcal vaccine recommendations. 
 

 

 

Cost $/QALY Saved by Scenarios (Stoecker Model) 

PCV15, PCV15 + PPSV23, PCV20, PCV20, 

≥65 years ≥65 years (ICER) ≥50 years ≥65 years

Base Case 158,025 +462,604 Cost-saving Cost-saving 

One-way sensitivity analyses 

Indirect effects 507,445 +483,075 24,625 Cost-saving 

from children 

PCV VE=0% vs. Dominated* +330,183 Cost-saving Cost-saving 

ST 3 disease 

Improved PCV15 117,066 +476,768 NA NA 

VE vs. ST 3 

disease 

*Dominated: the new option is more costly and less effective compared to the current recommendation. 

ICER: incremental cost-effectiveness ratio compared to PCV15 only age ≥65 years
 

 

 

Cost $/QALY Saved by Scenarios (Stoecker Model) 

PCV15, PCV15 + PPSV23, PCV20, PCV20, 

≥65 years ≥65 years (ICER) ≥50 years ≥65 years

Base Case 158,025 +462,604 Cost-saving Cost-saving 

One-way sensitivity analyses 

Indirect effects 

from children 

507,445 +483,075 24,625 Cost-saving 

PCV VE=0% vs. 

ST 3 disease 

Dominated* +330,183 Cost-saving Cost-saving 

Improved PCV15 

VE vs. ST 3 

disease 

117,066 +476,768 NA NA 

*Dominated: the new option is more costly and less effective compared to the current recommendation. 

ICER: incremental cost-effectiveness ratio compared to PCV15 only age ≥65 years
 

 

 

Cost $/QALY Saved by Scenarios (Stoecker Model) 

PCV15, PCV15 + PPSV23, PCV20, PCV20, 

≥65 years ≥65 years (ICER) ≥50 years ≥65 years

Base Case 158,025 +462,604 Cost-saving Cost-saving 

One-way sensitivity analyses 

Indirect effects 

from children 

507,445 +483,075 24,625 Cost-saving 

PCV VE=0% vs. 

ST 3 disease 

Dominated* +330,183 Cost-saving Cost-saving 

Improved PCV15 

VE vs. ST 3 

disease 

117,066 +476,768 NA NA 

*Dominated: the new option is more costly and less effective compared to the current recommendation. 

ICER: incremental cost-effectiveness ratio compared to PCV15 only age ≥65 years
 

 

 

Cost $/QALY Saved by Scenarios (Stoecker Model) 

PCV15, PCV15 + PPSV23, PCV20, PCV20, 

≥65 years ≥65 years (ICER) ≥50 years ≥65 years

Base Case 158,025 +462,604 Cost-saving Cost-saving 

One-way sensitivity analyses 

Indirect effects 

from children 

507,445 +483,075 24,625 Cost-saving 

PCV VE=0% vs. 

ST 3 disease 

Dominated* +330,183 Cost-saving Cost-saving 

Improved PCV15 

VE vs. ST 3 

disease 

117,066 +476,768 NA NA 

*Dominated: the new option is more costly and less effective compared to the current recommendation. 

ICER: incremental cost-effectiveness ratio compared to PCV15 only age ≥65 years
 

 

Resource Use 

Is recommending PCV15 for persons aged ≥65 years a 

reasonable and efficient allocation of resources? 

□ No 

□ Probably no 

□ Probably yes 

□ Yes 

□ Varies 

□ Don’t know 
 

 

Resource Use 

Is recommending PCV15 for persons aged ≥65 years in series

with PPSV23 a reasonable and efficient allocation of resources? 

□ No 

□ Probably no 

□ Probably yes 

□ Yes 

□ Varies 

□ Don’t know 
Resource Use 

 Is recommending PCV20 for persons aged ≥50 years a reasonable and 

efficient allocation of resources? 

 Is recommending PCV20 for persons aged ≥65 years a reasonable and 

efficient allocation of resources? 

□ No 

□ Probably no 

□ Probably yes 

□ Yes 

□ Varies 

□ Don’t know 
 

 

Work Group Interpretation: Resource Use 

EtR Domains PCV15, ≥65 years PCV15 +PPSV23, 

≥65 years

PCV20, ≥50 years PCV20, ≥65 years

Public Health Problem Yes 

Benefits and Harms 

a. Benefits Small Small Large Moderate-Large 

b. Harms Minimal 

c. Benefit>Harm? Favors intervention 

d. Overall certainty: 

effectiveness 

e. Overall certainty: safety 

Moderate 

High 

Values 

a. Desirable>Undesirable? Probably yes 

b. Uncertainty? Probably not important uncertainty or variability 

Acceptability Probably yes Varies Probably yes Yes 

Resource use Probably no No Yes Yes 

Note: Each policy question is compared to the current vaccine recommendation 
Equity 

What would be the impact on health equity? 
 

 

 

 

Groups or settings that might be disadvantaged in

relation to pneumococcal disease burden 

 Older adults1 

 Adults with certain underlying medical conditions2 

 Black population (vs. non-Black population)2 

 American Indian (AI)/Alaska Native (AN) population3 

 Adults living in impoverished census tracts4

Indirect effects from pediatric PCV vaccination reduced disparities 

in vaccine-type pneumococcal disease. 

1. ABCs, 2. ABCs and NHIS, 3. June 2019 ACIP meeting presentation, 4. Burton et al. AJPH 2010
IPD Incidence by Serotype Group in Adults Aged ≥65 Years by 

Race, 2017–2018 

0 

5 

10 

15 

20 

25 

30 

35 

IPD incidence by 100,000 population 

White Black Other 

PCV13 PCV15, non-PCV13 PCV20, non-PCV15 PPSV23, non-PCV20 NVT 

CDC ABCs, 2017–2018 
 

IPD Incidence by Serotype Group in Adults Aged ≥65 Years by 

Race, 2017–2018 Use of PCV15 or PCV20 in adults may reduce, but not 

eliminate racial disparities in invasive pneumococcal 35 disease burden in adults. 

30 

25 

20 

15 

10 

5 

0 

PCV13 PCV15, non-PCV13 PCV20, non-PCV15 PPSV23, non-PCV20 NVT 

IPD incidence by 100,000 population 

White Black Other 

CDC ABCs, 2017–2018 
 

 

 

 

 

 

The new PCVs may reduce the higher IPD burden in

AI/AN adults aged ≥50 years.

In adults aged ≥50 years,

 From 2011–2019, IPD incidence in AN1 was approximately 3x higher 

compared to non-AN adults in Alaska. 

 In 2019, IPD incidence in AI2 adults was approximately 4x higher 

compared to general US population3. 

– Additional PCV15 serotypes*: 6-7% (AI) to 9-13% (AN) of IPD 

– Additional PCV20 serotypes*: 28–31% (AN) to 31–35% (AI) of IPD 

AI: American Indian, AN: Alaska Native 

1 John Hopkins Center for American Indian Health, unpublished data; 2CDC, Arctic Investigations Program, unpublished data; 3. CDC ABCs 

*serotypes included in PCV15 or PCV20, but not in PCV13. serotype distribution data represents 2015–2020 for AI, 2011–2019 for AN 
 

 

Pneumococcal Vaccine Coverage in adults aged 19–64 years with 

indications has been low. 

Sample 

size % (95% CI) 

Overall 5,851 23.3% (22.0, 24.6)

White 4,048 23.6% (22.1, 25.2) 

Black 696 25.7% (21.8, 30.0) 

Hispanic 656 18.5% (15.2, 22.4)* 

Asian 192 25.0% (17.3, 34.5)

Other 259 25.8% (19.3, 33.5) 

National Health Interview Survey, 2018 

*p<0.05 for comparisons with white as the reference. 
 

 

Compared to Whites, Hispanics had significantly lower proportion of 

those who ever received pneumococcal vaccines. 

Sample 

size % (95% CI) 

Overall 5,851 23.3% (22.0, 24.6)

White 4,048 23.6% (22.1, 25.2) 

Black 696 25.7% (21.8, 30.0) 

Hispanic 656 18.5% (15.2, 22.4)* 

Asian 192 25.0% (17.3, 34.5)

Other 259 25.8% (19.3, 33.5) 

National Health Interview Survey, 2018 

*p<0.05 for comparisons with white as the reference. 
 

 

 

Coverage of recommended pneumococcal vaccines was lower in Medicare 

beneficiaries aged ≥65 years when both PCV13 and PPSV23 were 

recommended, and racial disparities existed. 

46% 

33% 31%

14% 

0% 

5% 

10% 

15% 

20% 

25% 

30% 

35% 

40% 

45% 

50% White 

Asian 

Native American 

Black 

Hispanic 

Any PPSV23 dose, 2013 PCV13+PPSV23, 2018 

*except for adults with 

immunocompromising conditions

CDC Unpublished Data PPSV23 only recommended* PCV13+PPSV23 recommended 
 

 

 

 

 

 

Lowering the age-based recommendation may

disadvantage those who are uninsured. 

 In 2019, the National Health Interview Survey1 reported that: 

– 14.7% aged 18–64 years vs. 0.9% aged ≥65 years uninsured 

 Among adults aged 18–64 years, groups more likely to be uninsured were: 

– Those who were poor/near poor (<200% of the federal 

poverty level) 

– Hispanics 

 Section 317-funded vaccines can be used to vaccinate the uninsured2 

1. https://www.cdc.gov/nchs/data/nhis/earlyrelease/insur202009-508.pdf 

2. https://www.cdc.gov/vaccines/imz-managers/guides-pubs/qa-317-funds.html 
 

 

 

 

Lowering the age-based recommendation may improve vaccine coverage in 

population with higher prevalence of conditions that increase the risk of 

pneumococcal disease at a younger age. 

Non-immunocompromising pneumococcal high-risk conditions: chronic heart, lung, or liver 

disease; diabetes mellitus; alcoholism; asthma; cirrhosis 

Nowalk et al. Journal of the National Medical Association 2019. 
 

 

Equity 

What would be the impact of recommending PCV15 in persons 

aged ≥65 years be on health equity? 

□ Reduced 

Probably reduced 

Probably no impact 

Probably increased 

Increased 

□

□

□

□

• A simplified recommendation may improve 

overall vaccine coverage 

• No PPSV23 lose coverage for 9 serotypes 
 

 

 

Equity 

What would be the impact of recommending PCV15 in persons 

aged ≥65 years in series with PPSV23 be on health equity? 

□

□

□

□

□

Reduced 

Probably reduced 

Probably no impact 

Probably increased 

Increased 

• A vaccine recommendation with 2 different 

vaccines is more likely to disadvantage those 

with challenges with healthcare access 
 

 

 

 

 

Equity 

What would be the impact of recommending PCV20 in persons 

aged ≥50 years be on health equity? 

□ Reduced 

□ Probably reduced 

□ Probably no impact 

□ Probably increased 

□ Increased 

• May potentially disadvantage uninsured adults 

• May improve vaccine coverage in adults with 

underlying conditions before age 65 years
 

 

Equity 

What would be the impact of recommending PCV20 in persons 

aged ≥65 years be on health equity? 

□

□

□

□

□

Reduced 

Probably reduced 

Probably no impact 

Probably increased 

Increased 

• May potentially disadvantage adults with 

limited access 

• A simplified recommendation may improve 

overall vaccine coverage 
 

 

Work Group Interpretation: Equity 

EtR Domains PCV15, ≥65 years PCV15 +PPSV23, 

≥65 years

PCV20, ≥50 years PCV20, ≥65 years

Public Health Problem Yes 

Benefits and Harms 

a. Benefits Small Small Large Moderate-Large 

b. Harms Minimal 

c. Benefit>Harm? Favors intervention 

d. Overall certainty: 

effectiveness 

Moderate 

e. Overall certainty: safety High 

Values 

a. Desirable>Undesirable? Probably yes 

b. Uncertainty? Probably not important uncertainty or variability 

Acceptability Probably yes Varies Probably yes Yes 

Resource use Probably no No Yes Yes 

Equity Probably no impact Probably reduced Probably increased Probably increased 

Note: Each policy question is compared to the current vaccine recommendation 
Feasibility 

Are the options feasible to implement? 
 

 

 

 

Feasibility: Summary of Work Group Interpretation 

 PCV-PPSV23 series has been recommended: feasible 

– May disadvantage people with challenges with access to vaccines 

 A recommendation that consists of a single vaccine dose is easier to 

implement and is likely to achieve coverage in a larger population. 
 

 

 

Feasibility 

□

□

□

□

□

□

No 

Probably no 

Probably yes 

Yes 

Varies 

Don’t know 

 Is recommending PCV15 for persons aged 

≥65 years feasible to implement? 

 Is recommending PCV20 for persons aged 

≥50 years feasible to implement? 

 Is recommending PCV20 for persons aged 

≥65 years feasible to implement? 
 

Feasibility 

Is recommending PCV15 for persons aged ≥65 years in series 

with PPSV23 feasible to implement? 

□

□

□

□

□

□

No 

Probably no 

Probably yes 

Yes 

Varies 

Don’t know 
 

 

Work Group Interpretation: Feasibility 

EtR Domains PCV15, ≥65 years PCV15 +PPSV23, ≥65 years PCV20, ≥50 years PCV20, ≥65 years

Public Health Problem Yes 

Benefits and Harms 

a. Benefits Small Small Large Moderate-Large 

b. Harms Minimal 

c. Benefit>Harm? Favors intervention 

d. Overall certainty: 

effectiveness 

Moderate 

e. Overall certainty: safety High 

Values 

a. Desirable>Undesirable? Probably yes 

b. Uncertainty? Probably not important uncertainty or variability 

Acceptability Probably yes Varies Probably yes Yes 

Resource use Probably no No Yes Yes 

Equity Probably no impact Probably reduced Probably increased Probably increased 

Feasibility Yes Probably yes Yes Yes 

Note: Each policy option is compared to the current vaccine recommendation 
 

 

 

Summary of Work Group Interpretation 

EtR Domains PCV15, ≥65 years PCV15 +PPSV23, ≥65 years PCV20, ≥50 years PCV20, ≥65 years

Public Health Problem Yes 

Benefits and Harms 

a. Benefits Small Small Large Moderate-Large 

b. Harms Minimal 

c. Benefit>Harm? Favors intervention 

d. Overall certainty: Moderate 

effectiveness 

e. Overall certainty: safety High 

Values 

a. Desirable>Undesirable? Probably yes 

b. Uncertainty? Probably not important uncertainty or variability 

Feasibility Yes Probably yes Yes Yes 

Acceptability Probably yes Varies Probably yes Yes 

Resource use Probably no No Yes Yes 

Equity Probably no impact Probably reduced Probably increased Probably increased 

Note: Each policy option is compared to the current vaccine recommendation, not across options 
 

 

 

Summary: Work Group Interpretations 

Should Merck PCV15 be recommended for persons aged ≥65 

years? 

Balance of 

consequences 

Undesirable 

consequences 

clearly 

outweigh 

desirable 

consequences 

in most 

settings 

Undesirable 

consequences 

probably 

outweigh 

desirable 

consequences 

in most 

settings 

The balance 

between 

desirable and 

undesirable 

consequences 

is closely 

balanced or 

uncertain 

Desirable 

consequences 

probably 

outweigh 

undesirable 

consequences 

in most 

settings 

Desirable 

consequences 

clearly 

outweigh 

undesirable 

consequences 

in most 

settings 

There is 

insufficient 

evidence to 

determine the 

balance of 

consequences 

• Cost-effectiveness analysis showed some benefits in preventing disease. 

• Concerns about losing coverage for 9 serotypes that are included in PPSV23. 
 

 

 

 

Summary: Work Group Interpretations 

Should Merck PCV15 be recommended for persons aged ≥65 

years in series with PPSV23? 

Balance of 

consequences 

Undesirable 

consequences 

clearly 

outweigh 

desirable 

consequences 

in most 

settings 

Undesirable 

consequences 

probably 

outweigh 

desirable 

consequences 

in most 

settings 

The balance 

between 

desirable and 

undesirable 

consequences 

is closely 

balanced or 

uncertain 

Desirable 

consequences 

probably 

outweigh 

undesirable 

consequences 

in most 

settings 

Desirable 

consequences 

clearly 

outweigh 

undesirable 

consequences 

in most 

settings 

There is 

insufficient 

evidence to 

determine the 

balance of 

consequences 

• PCV15-PPSV23 may prevent additional disease but added benefit likely small. 

• Potential undesirable consequences related to resource use, feasibility, and equity may 

outweigh the desirable consequences. 

• Some patients currently receive PCV13-PPSV23 series. 
 

 

 

Summary: Work Group Interpretations 

Should Pfizer PCV20 be recommended for persons aged ≥50 years? 

Should Pfizer PCV20 be recommended for persons aged ≥65 years? 

Balance of 

consequences 

Undesirable 

consequences 

clearly 

outweigh 

desirable 

consequences 

in most 

settings 

Undesirable 

consequences 

probably 

outweigh 

desirable 

consequences 

in most 

settings 

The balance 

between 

desirable and 

undesirable 

consequences 

is closely 

balanced or 

uncertain 

Desirable 

consequences 

probably 

outweigh 

undesirable 

consequences 

in most 

settings 

Desirable 

consequences 

clearly 

outweigh 

undesirable 

consequences 

in most 

settings 

There is 

insufficient 

evidence to 

determine the 

balance of 

consequences 
Next Steps 

 Additional cost-effective analyses underway 

 GRADE and EtR for risk-based recommendation for younger 

adults not targeted by the age-based recommendation 

– To be presented at the September ACIP meeting 

 Refine policy options on age- and risk- based 

recommendations on PCV15 and PCV20 use in adults for a 

vote at the October ACIP meeting 

– PCV15 and PCV20 will be reviewed separately 
 

 

 

 

 

 

 

 

 

Questions for ACIP members 

 Are there other age-based policy options we should be considering for 

GRADE and EtR? 

 Are there policy options we should not be considering for a vote? 

 Are there additional data the Committee would like to see before deciding 

on policy options? 

PCV15: 

Should Merck PCV15 be recommended for persons aged ≥65 years?

Should Merck PCV15 be recommended for persons aged ≥65 years in series with PPSV23?

PCV20:

Should Pfizer PCV20 be recommended for persons aged ≥50 years?

Should Pfizer PCV20 be recommended for persons aged ≥65 years?
 

 

 

 

 

 

Acknowledgements 

 ACIP and the Pneumococcal Work Group 

 Johns Hopkins Center for American Indian Health 

 CDC contributors and consultants: Tamara Pilishvili, Ryan Gierke, Jennifer 

Loo Farrar, Lana Childs, Amadea Britton, Fahmina Akhter, Mahamoudou 

Ouattara, Penina Haber, Pedro Moro, Sarah Schillie, Jessica Hoehner, Hilda 

Razzaghi, Walter Williams, Tammy Zulz, Marc Fischer, Andrew Leidner, 

Tandin Dorji, Wei Xing, Nong Shang, Rebecca Morgan, Doug OutcaltCampos 
 

 

 

Thank you 

For more information, contact CDC 

1-800-CDC-INFO (232-4636)

TTY: 1-888-232-6348 www.cdc.gov

The findings and conclusions in this report are those of the authors and do not necessarily represent the 

official position of the Centers for Disease Control and Prevention.