ACIP Evidence to Recommendations Framework

Last updated 20 Nov 2019 *See EtR Guide for additional information.

 ** When no evidence is available, provide transparent reflection by guideline panel on the matter.

Questions: Should PCV13 be administered routinely to all immunocompetent* adults aged ≥65 years in the context of indirect effects from 

pediatric PCV use experienced to date?

Population: Adults ≥65 years old, who do not have an immunocompromising condition**, cerebrospinal fluid (CSF) leak, or cochlear implant 

in the context of indirect effects from pediatric PCV use experienced to date

Intervention: PCV13 at ≥65 years old in series with PPSV23, in the context of indirect effects from pediatric PCV use experienced to date

Comparison(s): PPSV23 alone at ≥65 years old, in the context of indirect effects from pediatric PCV use experienced to date

Outcomes: Invasive pneumococcal disease (IPD), pneumonia, mortality, and PCV13 safety

*Immunocompetent defined in discussion as adults without an 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.

**Immunocompromising conditions include: chronic renal failure, nephrotic syndrome, immunodeficiency, iatrogenic immunosuppression, generalized

malignancy, HIV, Hodgkin disease, leukemia, lymphoma, multiple myeloma, solid organ transplants, congenital or acquired asplenia, sickle cell disease, or

other hemoglobinopathies.

Background: On August 13, 2014, ACIP recommended routine use of 13-valent pneumococcal conjugate vaccine (PCV13) in series with the 

23-valent pneumococcal polysaccharide vaccine (PPSV23) for adults aged ≥65 years. At the time, the recommendation was warranted because

PCV13-type disease burden, in particular PCV13-type pneumonia, was determined to be an important public health problem. However, in the

long-term ACIP recognized that continued indirect effects from pediatric PCV13 use could further reduce PCV13-preventable disease among

adults and may limit the utility of the recommendation for routine PCV13 use among adults ≥65 years old. Therefore, ACIP proposed that the

recommendation for routine PCV13 use among adults ≥65 years old be re-evaluated in 2018 and revised as needed.

CRITERIA JUDGMENTS EVIDENCE ADDITIONAL INFORMATION

PROBLEM

Is the problem 

of public 

health 

importance? 

No Probably

no

Uncertain Probably

yes

Yes Varies

X

Among adults ≥65 years old:

PCV13-type IPD incidence 

(2015–2017)[1]

• Incidence plateaued at

5/100,000 (20% of all

IPD)

• Common PCV13

serotypes (ST, % of all

IPD): 3 (15%), 19A (4%),

and 19F (2%)

PCV13-type pneumonia 

incidence (2015–2016)

• Incidence estimates range

across studies 17 to

76/100,000 (3.7% of allcause pneumonia)[2, 3]

• Common PCV13

serotypes (% of all-cause

Disparities in PCV13-type IPD incidence by age 

[1], ethnicity (Alaskan Natives and Navajos[5]), 

and presence of underlying medical conditions 

[6] have been reduced through indirect effects

from pediatric PCV13 use but not eliminated.

https://www.cdc.gov/vaccines/acip/recs/grade/PCV13-etr-h.pdf
ACIP Evidence to Recommendations Framework

Last updated 20 Nov 2019 *See EtR Guide for additional information.

 ** When no evidence is available, provide transparent reflection by guideline panel on the matter.

pneumonia): 3 (1.3%) 

and 19A (1%)[4]

BENEFITS & HARMS 

How 

substantial 

are the 

desirable 

anticipated 

effects?

Minimal Small Moderate Large Don’t 

know

Varies

X

Direct effects from PCV13 use 

among adults ≥65 years old: 

• PCV13 is 

effective/efficacious in 

preventing PCV13-type IPD 

and Non-Invasive 

Pneumococcal Pneumonia 

(NIPP) (See GRADE tables)

• No effectiveness/efficacy for 

all-cause or PCV13-type 

mortality demonstrated (See 

GRADE tables)

• Uncertainty about the 

benefits of PCV13 against 

ST3 disease; data indicates 

expected benefits are lower 

for ST3-type disease than for 

other PCV13-type disease [7]

• Estimated cases averted:

o 781 (95%CI: -63, 

1713) PCV13-type 

IPD cases among 

adults ≥65 years

nationwide, Aug 

2014–Mar 2018[1]

o 28,600 (95%CI: 

21,000– 36,600) 

pneumonia cases 

among Medicare 

Part A/B 

beneficiaries, Sep 

2014–Dec 2017[8]

• Vaccinating a cohort of 65 

year olds with PCV13 would 

prevent approximately 80 

IPD and 4,000–10,000 

pneumonia cases over the 

Indirect effects from PCV use among children 

reduced pneumococcal disease among adults ≥65 

years old

• PCV13 IPD declined by nine fold [1]

• All-cause pneumonia reductions observed in 

most studies [10, 11]

PCV13 VE against PCV13-type IPD and pneumonia 

decreases with increasing age at vaccination[12]

• 65% (95%CI: 38, 81) at age 65 years

• 40% (95%CI: 17, 56) at age 75 years

• Model did not converge at age 85 years
ACIP Evidence to Recommendations Framework

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 ** When no evidence is available, provide transparent reflection by guideline panel on the matter.

remaining lifetime of the 

cohort [9]

Population level impact since 

2014 (combined direct and 

indirect effects)

• No impact on PCV13-type 

IPD or mortality (plateau in 

rates)[1]

• Inconsistent data across 

studies for impact on 

pneumonia[2, 3]

CRITERIA JUDGMENTS RESEARCH EVIDENCE ADDITIONAL INFORMATION

How 

substantial 

are the 

undesirable 

anticipated 

effects?

 Minimal Small Moderate Large Don’t 

know

Varies

X

No concerning safety signals 

seen in studies since the 2014 

recommendations were made 

with at least 40% coverage 

among adults ≥65 years old.

(See GRADE tables)

There is no evidence by subgroup within the adult 

population ≥65 years old of the harms of PCV13 

use.

Do the 

desirable 

effects 

outweigh the 

undesirable 

effects?

Favors 

intervention

Favors 

comparison

Favors 

both

Favors 

neither

Unclear

X

Benefits of continued PCV13 use 

relatively small, but outweighed 

the risks, which are also small.
ACIP Evidence to Recommendations Framework

Last updated 20 Nov 2019 *See EtR Guide for additional information.

 ** When no evidence is available, provide transparent reflection by guideline panel on the matter.

What is the 

overall 

certainty of 

this evidence 

for the critical 

outcomes?

Effectiveness of the intervention

No

included

studies

4 

Very low

3 

Low

2

Moderate

1

High

X

Safety of the intervention

No

included

studies

4

Very low

3

Low

2

Moderate

1

High

X

Please see GRADE Tables and 

Summary.

Indirect effects: studies consistently demonstrate 

large magnitude impacts from pediatric PCV use on 

disease among adults ≥65 years old. 

Direct effects: PCV13 consistently demonstrated to 

be effective in post licensure studies. Inconsistent 

results across studies on the impact on disease: no 

impact on PCV13-type IPD or pneumococcal 

pneumonia, but decreased PCV13-type pneumonia 

and all-cause pneumonia.

Safety: PCV13 consistently demonstrated to be safe 

in post licensure studies.

SEULAV

Does the 

target 

population 

feel that the 

desirable 

effects are 

large relative 

to undesirable 

effects?

No Probably

no

Uncertain Probably

yes

Yes Varies

X

Evidence: very limited data 

available [13-15]

• Very few studies focus on 

older adult perceptions of 

PCV13 specifically

• Pneumonia perceived as 

severe (more so than 

influenza), sometimes fatal 

illness 

• Low perceived personal 

susceptibility to pneumonia 

Work group perspective: 

Most older adults would value the individual level 

protection from PCV13 vaccination above the side 

effects.

CRITERIA JUDGMENTS RESEARCH EVIDENCE ADDITIONAL INFORMATION

Is there 

important 

uncertainty 

about or 

variability in 

how much 

people value 

the main 

outcomes?

Important 

uncertainty 

or 

variability

Possibly 

important 

uncertainty 

or 

variability

Probably 

no 

important 

uncertainty 

or 

variability

No 

important 

uncertainty 

or variability

No known 

undesirable 

outcomes

X

No evidence identified for this 

domain.

Work group assessment: 

Uncertainty about how much adults ≥65 years old 

valued the main outcomes, but how important this 

uncertainty was could not be assessed further 

because of a lack of evidence.
ACIP Evidence to Recommendations Framework

Last updated 20 Nov 2019 *See EtR Guide for additional information.

 ** When no evidence is available, provide transparent reflection by guideline panel on the matter. ACCEPTABILITY

Is the 

intervention 

acceptable to 

key 

stakeholders?

No Probably

no

Uncertain Probably

yes

Yes Varies

X

Key findings from provider and 

immunization manager surveys 

[16-19]

• Current recommendations 

are confusing for providers

• Providers recommended 

continuing with current 

recommendation

• Keeping the current 

recommendations maybe 

best programmatically if 

new conjugate vaccines 

available soon

• Reimbursement for vaccine 

is still a programmatic issue

Frequent changes in recommendations may 

negatively impact the perceived importance of 

future adult vaccine recommendations. However, 

credibility comes from evidence-based 

recommendations. 

RESOURCE USE

Is the 

intervention a 

reasonable 

and efficient 

allocation of 

resources?

No Probably

no

Uncertain Probably

yes

Yes

X

Model Base 

case 

($/QALY)

Range 

($/QALY)

CDC 562,000* 112,000–

2.3 

million

Pfizer 199,000 46,000–

650,000

Pittsburgh765,000 461,000–

2.2 

million

*CDC base case estimate, 222,000 

when PCV13 VE for serotype (ST3) 

increased from 0% to 26% for ST3 

IPD and 45% for ST3 pneumonia

Greatest uncertainty in model inputs for:

• Pneumonia incidence

• PCV13 effectiveness against ST3 disease

• PPSV23 effectiveness against non-invasive 

pneumonia

 

Differences between models primarily due to:

• Vaccine effectiveness assumptions, especially 

PCV13 VE against ST3 pneumonia

• Other less important assumptions

o Case-fatality ratios

o Duration of indirect effects

o Utility assumptions

Reference [9]
ACIP Evidence to Recommendations Framework

Last updated 20 Nov 2019 *See EtR Guide for additional information.

 ** When no evidence is available, provide transparent reflection by guideline panel on the matter. FEASIBILITY

Is the 

intervention 

feasible to 

implement?

No Probably

no

Uncertain Probably

yes

Yes Varies

X

Universal prevention strategies 

are easier to adhere to than to 

risk-based ones. 

Recommendations are complex, 

but integrated into many health 

care and public health systems.

Frequent changes to recommendations present 

implementation challenges.

Change in recommendations could reduce access.

Discontinuing PCV13 use among older adults would 

simplify the recommendations, potentially 

improving adherence.

Effective communication strategies will be needed 

if a policy change occurs.

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

Opinion varies across the spectrum of this domain.

Is there sufficient information to move forward with a recommendation?

Yes X 

Type of 

recommendation

We do not recommend the 

intervention

We recommend the intervention for 

individuals based on shared clinical 

decision-making

We recommend the intervention

A majority of workgroup members proposed voting first on the policy to recommend PCV13 for all adults 65 years and older. 

This is the current policy and the framing of the policy question. However, when asked which of the three policy options 

workgroup members favored, the majority favored a change in the current policy. Most of those who favored a change 

thought that PCV13 should no longer be recommended for older adults.
ACIP Evidence to Recommendations Framework

Last updated 20 Nov 2019 *See EtR Guide for additional information.

 ** When no evidence is available, provide transparent reflection by guideline panel on the matter.

Recommendation 

(text)

A. Recommend PCV13: “ACIP recommends PCV13 for all adults 65 years or older who have not previously received PCV13. 

PCV13 should be given first, followed by a dose of PPSV23.”

B. Shared clinical decision making: “ACIP recommends PCV13 based on shared clinical decision making for adults 65 years or 

older who do not have an immunocompromising condition**, cerebrospinal fluid (CSF) leak, or cochlear implant and who 

have not previously received PCV13. All adults 65 years or older should receive a dose of PPSV23.”

C. No longer recommend PCV13: “ACIP no longer recommends PCV13 for adults 65 years or older who do not have an 

immunocompromising condition**, cerebrospinal fluid (CSF) leak, or cochlear implant. All adults 65 years or older should 

receive a dose of PPSV23.”

**Immunocompromising conditions include: chronic renal failure, nephrotic syndrome, immunodeficiency, iatrogenic 

immunosuppression, generalized malignancy, HIV, Hodgkin disease, leukemia, lymphoma, multiple myeloma, solid organ transplants, 

congenital or acquired asplenia, sickle cell disease, or other hemoglobinopathies.

Additional 

considerations

(optional)

Reasons in favor of discontinuing routine PCV13 use:

• Indirect effects from pediatric PCV use have reduced the burden of PCV13-type disease to historic lows

• Overall impact on PCV13-type disease from vaccinating older adults observed to date is minimal; no impact on IPD and 

inconsistent findings across studies for impact on pneumonia

• Benefits from continued PCV13 use are expected to be minimal

• Credibility comes from evidence-based recommendations

• Economic analyses results do not favor continued PCV13 use 

• Discontinuing PCV13 use among older adults would simplify the recommendations, potentially improving adherence

Reasons in favor of continuing routine PCV13 use:

• PCV13-type disease has been greatly reduced but not eliminated through indirect effects from pediatric PCV use

• PCV13 is effective in preventing PCV13-type pneumococcal disease

• A recommendation change would incur a cost to update electronic medical records, and decision support tools

• Universal prevention strategies are easier to implement effectively than risk-based ones 

• Frequent changes in recommendations may negatively impact the perceived importance of future adult vaccine 

recommendations and may present implementation challenges

i This Evidence to Recommendation table is based on the GRADE Evidence to Decision framework developed through the DECIDE project. Further 

information is available athttp://www.decide-collaboration.eu/evidence-decision-etd-framework
ACIP Evidence to Recommendations Framework

Last updated 20 Nov 2019 *See EtR Guide for additional information.

 ** When no evidence is available, provide transparent reflection by guideline panel on the matter.

Final deliberation and decision by the ACIP

Final ACIP 

recommendation

ACIP does not recommend the 

intervention

ACIP recommends the intervention 

for individuals based on shared 

clinical decision-making 

X

ACIP recommends the intervention

ACIP 

considerations

On June 26, 2019, ACIP voted to change the policy and recommended PCV13 based on shared clinical 

decision making for adults ≥65 years old who do not have an immunocompromising condition**, 

cerebrospinal fluid (CSF) leak, or cochlear implant and who have not previously received PCV13. All adults 

≥65 years old should continue to receive one dose of PPSV23. If the decision is made to give PCV13, it 

should be given ≥1 year before PPSV23. A full description of the deliberations and votes that lead to this 

decision can be found in the MMWR policy note, Table 3.

**Immunocompromising conditions include: chronic renal failure, nephrotic syndrome, immunodeficiency, iatrogenic immunosuppression, 

generalized malignancy, HIV, Hodgkin disease, leukemia, lymphoma, multiple myeloma, solid organ transplants, congenital or acquired 

asplenia, sickle cell disease, or other hemoglobinopathies.

References:

1. Pilishvili T, Gierke R, Xing W, et al. Changes in invasive pneumococcal disease (IPD) among adults following 6 years of 13-valent 

pneumococcal conjugate vaccine use in the U.S. Presented at the International Symposium on Pneumococci and Pneumococcal 

Diseases, Melbourne, Australia; April 15–19, 2018. 

2. Gierke R. Estimating impact of 13-valent pneumococcal conjugate vaccine on pneumococcal pneumonia among US adults. Presented 

at the Advisory Committee on Immunization Practices meeting, Atlanta, GA; October 2018

3. Swerdlow D. Incidence of community-acquired pneumonia in a US adult population. Presented at the Advisory Committee on 

Immunization Practices meeting, Atlanta, GA; October 2018. 

4. Pfizer. 1147 Non-Invasive Pneumonia Network. unpublished 2019.

5. Hammitt L. Pneumococcal carriage and disease in Native Americans in the era of routine use of PCV13 (data from John Hopkins 

Center for American Indian Health and CDC's Arctic Investigations Program). Presented at the Advisory Committee on Immunization 

Practices meeting, Atlanta, GA; June 2018. 
ACIP Evidence to Recommendations Framework

Last updated 20 Nov 2019 *See EtR Guide for additional information.

 ** When no evidence is available, provide transparent reflection by guideline panel on the matter.

6. Ahmed SS, Pondo T, Xing W, et al. Early impact of 13-valent pneumococcal conjugate vaccine use on invasive pneumococcal disease 

among adults with and without underlying medical conditions—United States. Clin Infect Dis 2019 Epub August 12, 2019. PubMed

https://doi.org/10.1093/cid/ciz739

7. Pilishvili T. 13-valent pneumococcal conjugate vaccine (PCV13) effects on disease caused by serotype 3. Presented at the Advisory 

Committee on Immunization Practices meeting, Atlanta, GA; February 2019. 

8. Lessa FC, Spiller M. Effectiveness of PCV13 in adults hospitalized with pneumonia using Centers for Medicare & Medicaid data, 2014–

2017. Presented at the Advisory Committee on Immunization Practices meeting, Atlanta, GA; February 2019. 

9. Leidner AJ. Overview of three economic analyses of pneumococcal vaccinations at age 65. Presented at the Advisory Committee on 

Immunization Practices meeting, Atlanta, GA; February 2019. 

10. Tsaban G, Ben-Shimol S. Indirect (herd) protection, following pneumococcal conjugated vaccines introduction: A systematic review of 

the literature. Vaccine 2017;35:2882–91. PubMed https://doi.org/10.1016/j.vaccine.2017.04.032

11. Lessa FC. Impact of introduction of infant vaccination with 13-valent pneumococcal conjugate vaccine (PCV13) on pneumonia and 

invasive pneumococcal disease (IPD) in the United States, 2005–2014. Presented at the Advisory Committee on Immunization 

Practices meeting, Atlanta, GA; October 2018

12. van Werkhoven CH, Hollingsworth RC, Huijts SM, et al. Pneumococcal conjugate vaccine herd effects on non-invasive pneumococcal 

pneumonia in elderly. Vaccine 2016;34:3275–82. Pub Med https://doi.org/10.1016/j.vaccine.2016.05.002

13. Doshi A. Knowledge of updated pneumococcal vaccine recommendations and evaluation of perceived susceptibility, severity, benefits, 

 and barriers to vaccination among adults aged 65 years and older. Journal of the American Pharmacists Association 2016;56:e56–7.

 https://www.japha.org/article/S1544-3191(16)30033-4/pdf

14. Brown T, Goldman SN, Acosta F, et al. Understanding Black Patients' Refusal of Pneumococcal Vaccination. Journal of Racial & Ethnic

Health Disparities 2017;4:1–8. Pub Med https://doi.org/10.1007/s40615-015-0193-9

15. Kaljee LM, Kilgore P, Prentiss T, et al. "You need to be an advocate for yourself": Factors associated with decision-making regarding 

influenza and pneumococcal vaccine use among US older adults from within a large metropolitan health system. Human vaccines &

Immunotherapeutics 2017;13:206–12. Pub Med https://doi.org/10.1080/21645515.2016.1228503

16. Hurley LP, Allison MA, Pilishvili T, et al. Primary Care Physicians' Struggle with Current Adult Pneumococcal Vaccine 

Recommendations. Journal of the American Board of Family Medicine: JABFM 2018;31:94–104. Pub Med

https://doi.org/10.3122/jabfm.2018.01.170216

17. Hurley LP. Survey on Adult Pneumococcal Vaccination. unpublished 2019.

18. Pfizer. Preferences for Adult Pneumococcal Vaccine Recommendations among US Health Care Providers. unpublished 2018.

19. Association of Immunization Managers A. AIM member survey. unpublished 2018.