Evidence to Recommendations for PCV13 use among adults ≥65 years old

About

The Evidence to Recommendations (EtR) frameworks describe information considered in moving from evidence to ACIP vaccine recommendations.

Summary

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

Outcome: 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.

Problem

References in this table123456

Criteria Work Group Judgments Evidence Additional Information
Is the problem of public health importance? Probably yes 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 all-cause pneumonia)[2, 3]
  • Common PCV13 serotypes (% of all-cause pneumonia): 3 (1.3%) and 19A (1%)[4]
 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.

Benefits and Harms

References in this table123789101112

Criteria Work Group Judgments Research Evidence Additional Information
How substantial are the desirable anticipated effects? Small 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:
    • 781 (95%CI: -63, 1713) PCV13-type IPD cases among adults ≥65 years nationwide, Aug 2014–Mar 2018[1]
    • 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 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]
 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
How substantial are the undesirable anticipated effects? Minimal 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 Benefits of continued PCV13 use relatively small, but outweighed the risks, which are also small.
What is the overall certainty of this evidence for the critical outcomes? Effectiveness of the intervention is Level 3 (Low)

Safety of the intervention is Level 2 (Moderate)

 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.

Values

References in this table131415

Criteria Work Group Judgments Research Evidence Additional Information
Does the target population feel that the desirable effects are large relative to undesirable effects? Uncertain 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.
Is there important uncertainty about or variability in how much people value the main outcomes? Possibly important uncertainty or variability 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.

Acceptability

References in this table16171819

Criteria Work Group Judgments Research Evidence Additional Information
Is the intervention acceptable to key stakeholders? Varies 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

Reference in this table9

Criteria Work Group Judgments Research Evidence Additional Information
Is the intervention a reasonable and efficient allocation of resources? Probably no
Model Base case ($/QALY) Range ($/QALY)
CDC 562,000* 112,000–

2.3 million
Pfizer 199,000 46,000–650,000
Pitts-burgh 765,000 461,000–

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
    • Case-fatality ratios
    • Duration of indirect effects
    • Utility assumptions

Reference [9]

Feasibility

Criteria Work Group Judgments Research Evidence Additional Information
Is the intervention feasible to implement? Probably yes 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

Opinion varies across the spectrum of this domain.

Is there sufficient information to move forward with a recommendation? Yes

Type of recommendation

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.

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

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

Final deliberation and decision by the ACIP

Final ACIP recommendation

ACIP recommends the intervention for individuals based on shared clinical decision-making

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..

This Evidence to Recommendation table is based on the GRADE Evidence to Decision framework developed through the DECIDE project. See further information.

View the complete list of EtR Frameworks‎‎‎

List of Evidence to Recommendations Framework Tables
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Content Source:
National Center for Immunization and Respiratory Diseases (NCIRD)
  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.
  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.
  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.
  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.
  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://dx.doi.org/10.1016/j.japh.2016.03.014
  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.
  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.
  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.
  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.