1

Economic Assessment of PCV15 & PCV20

Charles Stoecker

Tulane University

School of Public Health and Tropical Medicine

ACIP

June 25, 2021
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Conflicts of Interest

 Dr. Stoecker has no conflicts of interest to declare.
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Methods: Study Question

 Evaluate cost effectiveness of using PCV15 or PCV20 in 

adults

 Evaluate adding PPSV23 to either of these recommendations

 Evaluate

 Program cost/savings

 Changes in disease, medical costs, and nonmedical costs

• Societal perspective

 Population

• Cohort of 4,256,608 19 year olds

• Separate model buckets for:

o Immunocompromised (IC) – HIV, Cancer, Organ Transplants, 

Dialysis

o Chronic medical conditions (CMC)– Diabetes, Heart Disease, Lung 

Disease, Liver Disease, Alcoholism

o Others –”healthy”
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Methods: Interventions

 Eight strategies to evaluate

 PCV15 at CMC/IC & Age 50

• PCV15 at diagnosis of immunocompromising (IC) or chronic medical condition 

(CMC) for adults 19-49 plus PCV15 at age 50 (no PCV revaccination)

 PCV20 at CMC/IC & Age 50

 PCV15 at CMC/IC & Age 65

 PCV20 at CMC/IC & Age 65

 PCV15+PPSV at CMC/IC & Age 50

• As above, but with PPSV at diagnosis of IC or CMC or age 50

 PCV20+PPSV at CMC/IC & Age 50

 PCV15+PPSV at CMC/IC & Age 65

 PCV20+PPSV at CMC/IC & Age 65

 Compare to current recommendations

 PCV13 at diagnosis of IC, PPSV23 eight weeks later, 2nd dose of PPSV23 5 years 

later if under age 65

 PPSV23 at diagnosis of CMC

 PCV13 under shared clinical decision making at age 65, PPSV23 one year later
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Methods: Economic Model

 Cohort Model

 Cost per quality adjusted life year gained

 Cost per life year gained

 Use a cohort of 19-year-olds

 Compare each recommendation to status quo and 

calculate incremental cost effectiveness ratio

 Divide change in costs by change in Quality Adjusted Life Years 

(QALYs)

 Costs in April, 2021$

 Inflated by the Health Care component of Personal Consumption 

Expenditures

 Outcomes Discounted by 3%
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Methods: Health Outcomes

 Cases of Invasive Pneumococcal Disease (IPD)

 Cases of hospitalized Nonbacteremic Pneumonia (NBP)

 Cases of outpatient NBP

 Deaths due to IPD

 Deaths due to NBP

 QALYs

 Life Years
7

Conceptual Model
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CAP Hospitalization Rates per 100k

2013-2015

Source: MarketScan & Optum databases (Pelton et al. CID 2019) (95% CIs in parenthesis)

19-49 50-64 65-74 75+

Healthy 35 (35, 36) 88 (87, 90) 191 (185, 197) 957 (938, 975)

CMC 207 (202, 212) 429 (423, 425) 941 (925, 957) 2745 (2717, 2774)

IC 701 (681, 721) 1226 (1207, 1244) 2124 (2087, 2162) 3676 (3623, 3730)
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IPD Rates per 100k

Source: Active Bacterial Core Surveillance System, 2017-2018

19-49 50-64 65-74 75+

Healthy 2.09 6.09 8.25 19.27

CMC 8.09 24.04 25.89 40.06

IC 16.22 37.28 35.10 39.47
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Serotype Distributions, Healthy

50-64 65-74 75+

%PCV13 (+6C-3-19F) 10.41% 7.99% 8.98%

%serotype 3 14.53% 15.45% 14.79%

%serotype 19F 3.57% 4.55% 1.34%

% PCV15 only (ST 22F, 33F) 17.53% 13.12% 15.23%

% PCV 20 only (ST 8, 10A, 11A, 12F, 15B/C) 19.74% 18.84% 12.54%

% PPSV23 only (ST 2, 9N, 17F, 20) 11.23% 10.26% 8.07%

50-64 65+

PCV13-ST3 1.97 2.22

ST3 1.87 1.88

PCV15only 0.93 1.03

PCV20only 2.9 2.22

PPSV23only 2.39 1.2

% IPD (ABCs Data 2017-2018), Healthy

% Hospitalized All-Cause Pneumonia, Healthy
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19-49 50-64 65-74 75+

%PCV13 (+6C-3-19F) 18.54% 11.09% 6.65% 5.72%

%serotype 3 10.84% 17.27% 19.33% 16.05%

%serotype 19F 2.65% 2.61% 2.87% 2.16%

% PCV15 only (ST 22F, 33F) 11.98% 11.68% 12.09% 16.20%

% PCV 20 only (ST 8, 10A, 11A, 12F, 15B/C) 20.69% 18.00% 15.41% 13.12%

% PPSV23 only (ST 2, 9N, 17F, 20) 16.02% 13.69% 9.36% 6.48%

19-49 50+

PCV13-ST3 2.81 1.94

ST3 2.8 2.29

PCV15only 2.34 1.41

PCV20only 6.07 4.59

PPSV23only 2.34 3.35

Serotype Distributions, CMC

% IPD (ABCs Data 2017-2018), CMC

% Hospitalized All-Cause Pneumonia, CMC & IC
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19-49 50-64 65-74 75+

%PCV13 (+6C-3-19F) 11.26% 11.34% 9.84% 9.75%

%serotype 3 8.79% 10.03% 12.32% 11.59%

%serotype 19F 2.48% 2.38% 2.45% 1.83%

% PCV15 only (ST 22F, 33F) 18.81% 12.41% 13.54% 17.38%

% PCV 20 only (ST 8, 10A, 11A, 12F, 15B/C) 13.74% 15.84% 17.25% 10.97%

% PPSV23 only (ST 2, 9N, 17F, 20) 10.02% 11.88% 7.39% 4.88%

Serotype Distributions, IC

% IPD (ABCs Data 2017-2018), IC
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Vaccine Effectiveness

PCV vs VT (except ST3) IPD: Bonten NEJM 2015 (per protocol)

PCV vs ST3 IPD: Point estimate from Pilishvili et al. ISPPD2018 abstract, lower bound set to 0, upper bound from Lewis 2020 ISPPD poster

PCV vs VT (except 3) NBP: Suaya Vaccine 2018; 1477-1483. 

PCV vs ST3 NBP: applied the ratio of IPD VE/Pneumonia VE for all PCV13 types to the point estimate for ST3 IPD VE. 

PPSV vs VT IPD: CDC meta-analysis of 7 studies using indirect cohort methods 4/15/2021 

PPSV vs VT NBP: Lawrence, 2020 (meta-analysis of 3 studies, Kim, Suzuki and Lawrence: 19.2% (0-39.1)

All IC estimates: Apply ratio of VE for IC in Djennad 2018 to estimates for Healthy/CMC

PCV15 & PCV20 VE: Hurley CID 2020; Stacy Human Vaccines & Immunotherapeutics 2019

Healthy/CMC IC

PCV vs VT IPD 75 (41.4, 90.8) 27.1 (15, 32.8)

VE PCV vs VT IPD (Direct, ST3) 26 (0, 53.4) 9.4 (0, 19.3)

PCV vs VT (except 3) NBP (Healthy) 66.7 (11.8, 89.3) 16.3 (5.1, 23.6)

PCV vs VT (except 3) NBP (CMC) 40.3 (11.4, 60.2) .

PCV vs ST3 NBP 15.6 (0, 32.04) 6 (0, 11)

PPSV vs VT IPD 33 (27.3, 38.3) 11.9 (9.9, 13.8)

PPSV vs VT NBP 20 (0, 40) 7 (0, 14)
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Coverage Rates

 Risk-based recommendation 23.3% (21.8, 24.3)

 NHIS 2018

 Age-based recommendation at 50 38.83% (22.5, 55.15)

 Mean of NHIS 2018 coverage for Zoster 60-64 (22.5%) and age-based 

recommendation at age 65 below (55.15%)

 Age-based recommendation at 65 PCV 46.15% (43.3, 49)

 Mean of McLaughlin et al. 2019. (43.3%) and any PCV13 coverage in 

Medicare beneficiaries (49%)

 Age-based recommendation at 65 PPSV 55.15% (49, 61.3)

 Mean of NHIS 2014 data for any pneumococcal vaccine (49%) and any 

PPSV23 coverage data in Medicare beneficiaries aged ≥65 years, 2019 

(61.3%)

Bounds of beta-pert distributions in parenthesis
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Methods: Inputs

Herd Effects from PCV15 or PCV20 in Children

 Apply serotype group -specific declines observed in 

PCV13 types (+6C, -3, -19F) in adults after PCV13 

introduction in children

 Apply to additional types in PCV15 starting in 2023 

 Apply to additional types in PCV20 starting in 2024

 Run versions of the model with and without these herd 

effects to assess importance
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Methods: Inputs

Utility Decrements

Variable QALYs Healthy Days Lost

IPD 0.0709 

(0.0509, 0.0909) 25.9

IPT NBP 0.0709 

(0.0509, 0.0909) 25.9

OPT NBP 0.0045 

(0.00399, 0.00501) 1.6

QALY values from Mangen et al. 2015 Eur Respir J (95% CIs in parenthesis)

Duration of illness calculations assume a day in the hospital is worth 20% of a healthy day (Sisk et al. 2003 Ann. Intern. Med.)

Implied duration of hospitalization: 32.4 days
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Waning Immunity Assumptions

 PCV13/15/20

 No decline in effectiveness until age 65a

 Scenario 1:

• 10% every 5 years starting at age 65b

 Scenario 2:

• Linear decline to zero between 70 and 85c

 PPSV23d

 Declines in effectiveness start at vaccination

 Linear decline to 50% of initial over first 5 years

 Linear decline to 30% of initial over next 5 years

 Linear decline to 0% of initial over next 5 years

aPatterson S, Webber C, Patton M, Drews W, Huijts SM, Bolkenbaas M, et al. A post hoc assessment of duration of protection in CAPiTA

(Community Acquired Pneumonia immunization Trial in Adults). Trials in Vaccinology. 2016;5.:92-96.

bBy assumption. cvan Werkhoven CH, Huijts SM, Bolkenbaas M, Grobbee DE, Bonten MJ. The Impact of Age on the Efficacy of 13-valent Pneumococcal 

Conjugate Vaccine in Elderly. Clin Infect Dis 2015;61(12):1835-8.

dFry AM, Zell ER, Schuchat A, Butler JC, Whitney CG. Comparing Potential Benefits of New Pneumococcal Vaccines with the Current 

Polysaccharide Vaccine in the Elderly. Vaccine 2002;21:303-311.
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Waning

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1

% Initial Effectiveness

50 52 54 56 58 60 62 64 66 68 70 72 74 76 78 80 82 84 86 88 90 92 94 96 98 100

Age

Vaccination at 50

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1

65 67 69 71 73 75 77 79 81 83 85 87 89 91 93 95 97 99

% Initial Effectiveness

Age

Vaccination at 65

PPSV

PCV Linear

PCV 10%/5yrs
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Vaccine Price

 PCV13 $211.86a

 PCV15 $228.81a

 PCV20 $233.05a

 PPSV23 $110.45a

 Administration 19 -64 $29.16b

 Administration 65+ $23.60 c

 Travel + Patient Time cost: $42.52d

a Communication with manufacturers

b Tsai et al. AJPM 2019.

c Average Medicare maximum allowable reimbursement for immunization administration (HCPCS code 90471) across all MACs

d travel cost from Maciosek et al. Am J Prev Med 2006.
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Disease Cost ($)

All costs from 2016-2019 inflated to April 2021. Costs for <65 come from MarketScan databases. Costs for 65+ from CMS Medicare Data. 

Bootstrapped 95% CIs shown in parenthesis and used as inputs in normal distribution.

Otherwise Healthy CMC IC

Age 19-49 50-64 65+ 19-49 50-64 65+ 19-49 50-64 65+

IPD 57,278 55,408 27,372 53,523 49,372 25,705 90,729 121,544 35,510

(50,148, 

65,152)

(51,752, 

59,239)

(26,997, 

27,758)

(32,028, 

79,224)

(40,029, 

60,380)

(23,787, 

27,793)

(53,654, 

144,561)

(93,951, 

149,252)

(34,808, 

38,387)

IPT NBP 24,798 26,464 18,688 31,278 29,037 16,202 39,650 36,337 22,427

(24,254, 

25,343)

(25,997, 

26,979)

(18,659, 

18,715)

(27,581, 

35,593)

(27,362, 

30,820)

(16,086, 

16,320)

(32,843, 

48,404)

(33,319, 

39,634)

(22,277, 

22,585)

OPT NBP 775 709 630 1,038 876 588 1,208 1,062 943

(765, 

784)

(701, 

716)

(629, 

632)

(955, 

1,127)

(829, 

923)

(583, 

593)

(1,101, 

1,329)

(995, 

1,135)

(935, 

952)
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Scenarios

 Base Case

 PCV 0 VE vs ST3

 Assume all PCVs have no effectiveness against serotype 3

 Short Run Herd Effects

 Model 4.1% decline per year in PCV15/PCV20 unique types

 Start PCV15 decline at age 53 for vaccination at age 50

 Start PCV20 decline at age 54 for vaccination at age 50

 Start PCV15 decline at age 68 for vaccination at age 65

 Start PCV20 decline at age 69 for vaccination at age 65

 PCV Steeper Waning

 Assume PCVs have linear decline in effectiveness between age 70 

and 85

 Enhanced PCV15 VE vs ST3

 Healthy/CMC: 41.6% vs IPD; 24.96% vs NPB

 IC: 15 vs IPD; 9 vs NPB
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Summary of Findings 

Across One-Way Sensitivity Analyses

($/QALY)

(1) (2) (3) (4) (5) (6) (7) (8)

PCV15, 

50

PCV20, 

50

ICER (1) 

+PPSV

ICER (2) 

+PPSV

PCV15, 

65

PCV20, 

65

ICER (5) 

+PPSV

ICER (6) 

+PPSV

Base Case 282,711 CostSaving 574,871 1,635,228 158,025 CostSaving 462,604 1,313,935

PCV 0 VE vs ST3 1,133,404 CostSaving 403,527 792,145 Dominated CostSaving 330,183 658,782

Short Run Herd Effects 817,889 24,625 595,673 1,635,228 507,445 CostSaving 483,075 1,313,935

Steeper Waning 603,452 4,951 574,871 1,635,228 1,164,689 CostSaving 464,388 1,326,755

Enhanced PCV15 VE 231,267 583,149 117,066 476,768
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Base Case Vax at 50

PCV15 at 

CMC/IC & 

Age 50

PCV20 at 

CMC/IC & 

Age 50

ICER 

Adding 

PPSV to 

Column 1

ICER 

Adding 

PPSV to 

Column 2

Health Outcomes

IPD Cases -153 -500 -54 -24

Hospitalized Pneumonia Cases -194 -2,914 -175 -51

Non-hospitalized Pneumonia Cases -225 -7,401 -1,069 -312

Deaths due to IPD -22 -67 -6 -3

Deaths due to Pneumonia -10 -110 -4 -1

QALYs 193 1,378 156 59

Life-years 274 1,976 199 76

Costs (million $)

Total Cost $55 -$16 $90 $96

Medical Costs -$11 -$85 -$9 -$3

Vaccine Costs $66 $69 $99 $99

Cost Ratios ($)

Cost/QALY 282,711 Cost-Saving 574,871 1,635,228

Cost/Life-year 199,968 Cost-Saving 451,630 1,265,201
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Base Case Vax at 65

PCV15 at 

CMC/IC & 

Age 65

PCV20 at 

CMC/IC & 

Age 65

ICER 

Adding 

PPSV to 

Column 1

ICER 

Adding 

PPSV to 

Column 2

Health Outcomes

IPD Cases -116 -435 -106 -48

Hospitalized Pneumonia Cases -155 -2,822 -692 -227

Non-hospitalized Pneumonia Cases -55 -7,000 -2,076 -669

Deaths due to IPD -18 -60 -13 -6

Deaths due to Pneumonia -9 -107 -23 -8

QALYs 113 1,224 352 133

Life-years 181 1,801 516 196

Costs (million $)

Total Cost $18 -$50 $163 $175

Medical Costs -$8 -$79 -$19 -$6

Vaccine Costs $26 $28 $182 $182

Cost Ratios ($)

Cost/QALY 158,025 Cost-Saving 462,604 1,313,935

Cost/Life-year 98,566 Cost-Saving 315,857 893,281
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PCV15 at 

CMC/IC & 

Age 50

PCV15 at 

CMC/IC & 

Age 65

PCV20 at 

CMC/IC & 

Age 50

PCV20 at 

CMC/IC & 

Age 65

To Avert 1 Hospitalization 573 581 79 75

To Avert 1 Case 322 356 29 28

To Avert 1 Death 6,968 6,920 1,472 1,393

Number Needed to Vaccinate to Avert...

Base Case (No Herd Effects)
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Cost per Outcome Averted

Base Case (No Herd Effects)

PCV15 at 

CMC/IC & 

Age 50

PCV15 at 

CMC/IC & 

Age 65

PCV20 at 

CMC/IC & 

Age 50

PCV20 at 

CMC/IC & 

Age 65

To Avert 1 Hospitalization $157,895 $65,890

To Avert 1 Case $95,680 $54,718 Cost Saving

To Avert 1 Death $1,736,968 $672,283
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Vaccine Acceptability Curve

PCV20 at age 65

With Long Term Indirect Effects

0.00%

20.00%

40.00%

60.00%

80.00%

100.00%

 $- $200,000.00 $400,000.00 $600,000.00 $800,000.00 $1,000,000.00

Cumulative Density Function

(% of Iterations with Cost/QALY Below Indicated Value)

Cost Per QALY

 Substantial uncertainty introduced by potential herd effects

 69.7% of model iterations cost more than $100k/QALY

 61.1% more than $200k/QALY

 56.3% more than $300k/QALY

 38.8% of model iterations were dominated by current recommendations

 (Led to decreases in health and increases in cost)
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Existing Study

 Evaluation of PCV20 or PCV15 at age 65 (Smith et al. 

2021 AJPM)

 PCV20 $173k/QALY without indirect effects

 PCV20 $449k/QALY with indirect effects

 PPSV23 and PCV15 even less economically viable

 Key difference

 This evaluation includes risk-based recommendations bundled 

with age-based
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Limitations

 Work loss not considered

 Model assumed no vaccine adverse events

 Substantial uncertainty remains around the influence 

of

 Serotype 3 VE

 A PCV15/PCV20 childhood immunization program

 Vaccine waning

 Vaccine-preventable pneumonia burden
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Conclusions

(Given these assumptions and Limitations)

 Modeling indicated PCV20 was economically efficient 

at both ages 50 and 65 under several alternative 

scenarios

 PCV15 model findings were mixed even under 

optimistic assumptions about PCV15 VE vs serotype 3

 Adding PPSV23 to either PCV15 or PCV20 incurred high 

costs for minimal health gains in the model

 PCV20 less likely to be economically efficient under 

predicted indirect protection from the childhood 

program over the long term as modeled
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Thank you!

Please send comments to:

cfstoecker@tulane.edu

Contributors:

Miwako Kobayashi

Tamara Pilishvili

Bo-Hyun Cho

National Center for Immunization & Respiratory Diseases

HSREB – Econ Team