Document text
1Economic Assessment of PCV21 in U.S. Adults
Charles Stoecker
Tulane University
School of Public Health and Tropical Medicine
ACIP
June 27, 2024
2Conflicts of Interest
❑Dr. Stoecker has no conflicts of interest to declare.
3Acronyms
❑ PCV: pneumococcal conjugate vaccine
❑ PCV20: 20 valent PCV
❑ PCV21: 21 valent PCV
❑ VE: vaccine effectiveness
❑ VT: vaccine type
❑ ST: serotype
❑ NBP: non -bacteremic pneumonia
❑ IPD: invasive pneumococcal disease
❑ IPT: inpatient
❑ OPT: outpatient
❑ QALY: quality adjusted life year
❑ IC: immunocompromised
❑ CMC: chronic medical conditions, but not IC
❑ NIS: National Immunization Survey
❑ ABCs: Active Bacterial Core Surveillance System
4Methods: Study Question
❑Evaluate cost effectiveness of using PCV21 in adults
❑Evaluate
▪Program cost/savings
▪Changes in disease, medical costs, nonmedical costs, and work
productivity costs
•Limited societal perspective
▪Population
•Separate cohorts of 4,256,608 19 -year -olds, 3,990,700 42 -year -olds,
4,051,078 50 -year -olds, or 3,567,978 65 -year -olds for specific questions
•Separate model buckets for:
oImmunocompromised (IC) – HIV, Cancer, Organ Transplants,
Dialysis
oChronic medical conditions (CMC) – Diabetes, Heart Disease, Lung
Disease, Liver Disease, Alcoholism
oOthers –”General”
5Methods: Interventions
❑Five strategies to evaluate
Intervention Comparator
Question 1a Age -based vaccination at 65 with PCV21 Age -based vaccination at 65 with PCV20
Question 1b Risk -based vaccination with PCV21 Risk -based vaccination with PCV20
Question 2 Age -based vaccination at 50 with PCV21 Age -based vaccination at 65 with PCV21
Question 3 Age -based vaccination at 19 with PCV21 Age -based vaccination at 50 with PCV21
Supplemental PCV21 Dose after PCV20
Vaccination at 65 with PCV20 and 66 with PCV21
(all) Age -based vaccination at 65 with PCV20
Vaccination at 65 with PCV20 and 70 with PCV21
(all) Age -based vaccination at 65 with PCV20
Risk -based vaccination with PCV20 and
vaccination after 1 year with PCV21 (CMC/IC) Risk -based vaccination with PCV20
Risk -based vaccination with PCV20 and
vaccination after 5 years with PCV21 (CMC/IC) Risk -based vaccination with PCV20
6Methods: Economic Model
❑Cohort Model
▪Cost per quality adjusted life year (QALY) gained
▪Cost per life year gained
❑Compare each intervention to comparator strategy and
calculate incremental cost effectiveness ratio
▪Divide change in costs by change in QALYs
❑Costs in 2023$
▪Inflated by the Medical Care component of Consumer Price Index
❑Future costs and outcomes discounted by 3% annually
7Methods: Health Outcomes
❑
❑
❑
❑
❑
❑
❑Cases of Invasive Pneumococcal Disease (IPD)
Cases of Hospitalized (IPT) Nonbacteremic Pneumonia
(NBP)
Cases of outpatient (OPT) NBP
Deaths due to IPD
Deaths due to IPT NBP
QAL Ys
Life Y ears
8Conceptual Model
NBP
Background mortality from non-pneumococcus related illness is included in all branches, but not displayed in the model for brevity.IPT Case
IPT Case
OPT Case
9Model Inputs
❑
❑
❑IPD rates, all -cause IPT and OPT NBP rates, IPD cases resulting in
fatality were estimated by age - and risk group (general/CMC/IC).
Age -group specific IPT NBP case fatality rates were applied to all
risk groups
Vaccine effectiveness (VE) was estimated by risk group and
outcome (IPD/NBP).
▪
▪VE against serotype 3 was lower than other VT
VE was the same across PCV20 and PCV21
❑
❑Vaccine coverage was estimated by age group (19 –49, 50 –64, 65+)
and scenario (risk based, supplemental)
Herd inputs updated from previous iteration
▪
▪
▪New baseline estimation strategy
Bigger initial effect
Plateau after 6 years
See supplemental slides for the specific estimates used in the model.
10Serotype Group18-49
Years50-64
Years65-74
Years75-84
Years85+
Years
% PCV20 only -4-19F
(1, 5, 6B, 9V, 14, 18C, 23F, 15B, including
isolates reported as 15BC)1.99% 1.52% 3.09% 1.01% 1.08%
% PCV20 & PCV21 -3
(6A, 7F, 19A, 22F, 33F, 8, 10A, 11A, 12F) +6C 34.44% 41.95% 32.72% 32.32% 33.33%
% PCV21 only -35B
(9N, 17F, 20, 15A, 15C, 16F, 23A, 23B, 24F, 31)30.13% 30.70% 31.48% 29.29% 35.48%
% serotype 3 13.91% 12.46% 17.28% 21.21% 14.25%
% serotype 4 4.97% 2.43% 1.23% 0.00% 0.00%
% serotype 19F 4.97% 4.56% 3.70% 3.03% 3.01%
% serotype 35B 2.65% 0.91% 4.32% 5.05% 3.23%
Ratio PCV21 only:PCV20 only serotypes 2.75 3.71 4.46 8.50 9.46
Source: Active Bacterial Core Surveillance 2018 -2019. For multivariate sensitivity analyses distributions are beta -pert with -/+20% for low and high.IPD Serotype Distributions, General
11Serotype Group18-49
Years50-64
Years65-74
Years75-84
Years85+
Years
% PCV20 only -4-19F
(1, 5, 6B, 9V, 14, 18C, 23F, 15B, including
isolates reported as 15BC)0.49% 0.71% 1.88% 2.17% 1.81%
% PCV20 & PCV21 -3
(6A, 7F, 19A, 22F, 33F, 8, 10A, 11A, 12F) +6C 36.99% 33.62% 30.36% 32.79% 28.62%
% PCV21 only -35B
(9N, 17F, 20, 15A, 15C, 16F, 23A, 23B, 24F, 31)30.33% 32.67% 30.83% 32.52% 33.70%
% serotype 3 11.34% 17.96% 21.91% 17.07% 17.39%
% serotype 4 9.99% 4.35% 1.25% 0.27% 0.72%
% serotype 19F 3.08% 2.45% 2.66% 2.44% 2.17%
% serotype 35B 2.59% 3.01% 4.23% 5.15% 6.88%
Ratio PCV21 only:PCV20 only serotypes 2.43 4.75 6.06 7.72 8.63IPD Serotype Distributions, CMC
Source: Active Bacterial Core Surveillance 2018 -2019. For multivariate sensitivity analyses distributions are beta -pert with -/+20% for low and high.
12IPD Serotype Distributions, IC
Serotype Group18-49
Years50-64
Years65-74
Years75-84
Years85+
Years
% PCV20 only -4-19F
(1, 5, 6B, 9V, 14, 18C, 23F, 15B, including
isolates reported as 15BC)6.02% 3.92% 3.30% 2.88% 0.00%
% PCV20 & PCV21 -3
(6A, 7F, 19A, 22F, 33F, 8, 10A, 11A, 12F) +6C 28.92% 31.63% 30.03% 37.50% 48.31%
% PCV21 only -35B
(9N, 17F, 20, 15A, 15C, 16F, 23A, 23B, 24F, 31)31.33% 33.73% 33.99% 26.44% 25.84%
% serotype 3 15.66% 8.43% 11.55% 10.10% 4.49%
% serotype 4 1.20% 1.20% 1.32% 0.00% 0.00%
% serotype 19F 3.61% 3.61% 3.30% 1.44% 5.62%
% serotype 35B 6.02% 6.63% 8.91% 9.62% 5.62%
Ratio PCV21 only:PCV20 only serotypes 3.45 4.62 5.42 8.35 5.60
Source: Active Bacterial Core Surveillance 2018 -2019. For multivariate sensitivity analyses distributions are beta -pert with -/+20% for low and high.
13NBP Serotype Distributions
Serotype Group18-49
Years50-64
Years65+
Years
% PCV20 only -4-19F
(1, 5, 6B, 9V, 14, 18C, 23F, 15B)0.6% 0.7% 1.1%
% PCV20 & PCV21 -3
(6A, 7F, 19A, 22F, 33F, 8, 10A, 11A, 12F) +6C 3.0% 4.5% 3.9%
% PCV21 only -35B
(9N, 17F, 20, 15A, 15C, 16F, 23A, 23B, 24F, 31)3.2% 4.2% 2.4%
% serotype 3 1.1% 2.0% 1.4%
% serotype 4 0.0% 0.2% 0.2%
% serotype 19F 0.1% 0.9% 0.7%
% serotype 35B 0.8% 0.6% 0.7%
Ratio PCV21 only:PCV20 only serotypes 5.7 2.7 1.6
Source: Merck adjusted SSUAD serotype distribution data.
Note that the serotype distribution is among all community -acquired pneumonia, not limited to pneumococcal pneumonia.
For multivariate sensitivity analyses distributions are beta -pert with -/+20% for low and high.
14Waning Immunity Assumptions
❑
❑No decline in effectiveness for first five years a
Wane to zero over next 10 years b
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.
b van 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 -8.00.20.40.60.81
0 5 10 15 20% Initial Effectiveness
Years Since Vaccination
15Vaccine Price
❑
❑
▪
❑
❑
❑PCV20 $288.66a
PCV21 $319.43b
Sensitivity analysis with PCV21 price 5% higher ($335.60)
Administration 19 -64 years: $30.49c
Administration 65+ years: $21.07d
Travel + patient time cost: $44.46e
a Payment Allowance Limits for Medicare Part B for PCV20.
b Applied ratio of PCV21 to PCV20 price from manufacturer model and applied to PCV20 Medicare price. Sensitivity analysis uses upper bound of manufacturer
PCV21 price range.
c Tsai et al. AJPM 2019. Updated to 2023 dollars.
d Average Medicare maximum allowable reimbursement for immunization administration (HCPCS code 90471) across all Medicare Admin istrative Contractors,
2023.
e Travel cost from Maciosek et al. Am J Prev Med 2006. Updated to 2023 dollars.
16Sensitivity Analyses
❑
▪
❑
❑
▪
❑
▪
▪
❑Higher PCV21 Price
5% higher: $335.60 vs $319.43
No PCV20 type indirect protections for adults from
childhood program
Serotype 4 disease at 30% of pneumococcal disease
Decrease other serotypes proportionally to preserve overall
disease rates
Fix disease QAL Y decrements by age
Only for moving age -based recommendation to 19 or 50 years
Set QALY decrements to age 19 decrements for all ages
Alternate QAL Y decrements
17PCV21 Overview
Question 1a
PCV1 @Age 65Question 1b
PCV21 @CMC/ICQuestion 2
PCV21 @Age 50Question 3
PCV21 @Age 19
Health Outcomes
IPD Cases -889 ( -1099, -624) -194 ( -233, -139) 215 ( -101,534) 223 (112,339)
Hospitalized Pneumonia Cases -1630 ( -2210, -929) -368 ( -489, -207) 1050 (423,1751) 350 (159,544)
Non -hospitalized Pneumonia
Cases -3663 ( -5050, -2082) -1427 ( -1927, -801) 247 ( -1732,2421) 926 (77,1911)
Deaths due to IPD -108 ( -137, -74) -23 (-28,-16) 36 (-3,75) 28 (16,42)
Deaths due to Pneumonia -60 (-90,-31) -11 (-16,-6) 48 (14,86) 11 (4,20)
QALYs 1302 (926,1613) 363 (265,435) 52 (-633,744) -507 ( -759, -261)
Life-years 2082 (1476,2591) 513 (376,614) -389 ( -1331,564) -682 ( -1010, -360)
Costs (million $)
Total Cost 5 (-12,30) -29 (-38,-17) -5 (-119,121) 185 (111,254)
Medical Costs -60 (-74,-42) -26 (-31,-18) -34 (-74,9) 35 (18,51)
Vaccine Costs 90 (79,101) 12 (12,13) 75 (-108,258) 129 (40,219)
Work Loss -24 (-30,-17) -16 (-20,-11) -47 (-78,-16) 21 (9,33)
Cost Ratios ($)
Cost/QALY4,132 (C -S, 18,599) C-S (C-S, C-S)C-S (187,994*,
162,634) D (D, D)
Cost/Life -year2584 (C -S, 11,579) C-S (C-S, C -S)13,675* (89,406*,
214,539) D(D, D)
95% CI in parenthesis; * Indicates dollars saved per QALY or Life -year lost; C -S indicates cost -saving; D indicates dominated.
18Question 1a: Vaccination at age 65 with PCV21
BasePCV21 @
$335.60PCV20 Child
Indirect 0%Serotype 4 @
30%Tang QALY
Values
Health Outcomes
IPD Cases -889 -889 -855 152 -889
Hospitalized Pneumonia Cases -1,630 -1,630 -1,019 -422 -1,630
Non -hospitalized Pneumonia Cases -3,663 -3,663 -2,320 -807 -3,663
Deaths due to IPD -108 -108 -104 18 -108
Deaths due to Pneumonia -60 -60 -37 -16 -60
QALYs 1,302 1,302 1,098 -45 1,321
Life-years 2,082 2,082 1,771 -74 2,082
Costs (million $)
Total Cost $5 $37 $24 $85 $5
Medical Costs -$60 -$60 -$46 -$5 -$60
Vaccine Costs $90 $121 $90 $90 $90
Work Loss -$24 -$24 -$20 $1 -$24
Cost Ratios ($)
Cost/QALY 4,132 28,061 21,947 Dominated 4,073
Cost/Life -year 2,584 17,549 13,602 Dominated 2,584Cohort of 65 -year -olds. Comparator is PCV20 at age 65.
19Question 1b: Vaccination at CMC/IC with PCV21
BasePCV21 @
$335.60PCV20 Child
Indirect 0%Serotype 4 @
30%Tang QALY
Values
Health Outcomes
IPD Cases-194 -194 -188 29 -194
Hospitalized Pneumonia Cases-368 -368 -265 -190 -368
Non -hospitalized Pneumonia Cases
-1,427 -1,427 -1,128 -694 -1,427
Deaths due to IPD-23 -23 -22 3 -23
Deaths due to Pneumonia-11 -11 -8 -6 -11
QALYs363 363 324 29 361
Life-years513 513 458 32 513
Costs (million $)
Total Cost-$29 -$22 -$24 $3 -$29
Medical Costs-$26 -$26 -$22 -$7 -$26
Vaccine Costs$12 $19 $12 $12 $12
Work Loss-$16 -$16 -$14 -$3 -$16
Cost Ratios ($)
Cost/QALYCost -Saving Cost -Saving Cost -Saving 111,812 Cost -Saving
Cost/Life -year Cost -Saving Cost -Saving Cost -Saving 98,126 Cost -SavingCohort of 42 -year -olds. Comparator is PCV20 at CMC/IC.
20Question 1b: Vaccination at CMC/IC with PCV21
Cohort of 42 -year -olds. Comparator is PCV20 at CMC/IC.
Serotype 4 @
5%Serotype 4 @
10%Serotype 4 @
15%Serotype 4 @
20%Serotype 4 @
25%Serotype 4 @
30%Serotype 4 @
35%
Health Outcomes
IPD Cases -184 -141 -99 -56 -13 29 72
Hospitalized Pneumonia Cases -345 -314 -283 -252 -221 -190 -159
Non -hospitalized Pneumonia
Cases-1,327 -1,201 -1,074 -947 -821 -694 -567
Deaths due to IPD -21 -16 -11 -6 -2 3 8
Deaths due to Pneumonia -11 -10 -9 -8 -7 -6 -5
QALYs 345 282 218 155 92 29 -35
Life-years 486 395 304 214 123 32 -58
Costs (million $)
Total Cost -27 -21 -15 -9 -3 3 9
Medical Costs -24 -21 -17 -14 -10 -7 -3
Vaccine Costs 12 12 12 12 12 12 12
Work Loss -15 -13 -10 -8 -5 -3 0
Cost Ratios ($)
Cost/QALY Cost -Saving Cost -Saving Cost -Saving Cost -Saving Cost -Saving 111,812 Dominated
Cost/Life -year Cost -Saving Cost -Saving Cost -Saving Cost -Saving Cost -Saving 98,126 Dominated
Base case serotype 4 distributions are age, risk, and disease condition specific as displayed earlier in the slides. They ra nge from 0 to 9.99%
21Question 2: Vaccination at age 50
BasePCV21 @
$335.60PCV20 Child
Indirect 0%Serotype 4 @
30%Fix QALY
DecrementsTang QALY
Decrements
Health Outcomes
IPD Cases215 215 398 131 215 215
Hospitalized Pneumonia Cases1,050 1,050 2,220 775 1,050 1,050
Non -hospitalized Pneumonia
Cases247 247 2,175 282 247 247
Deaths due to IPD36 36 62 23 36 36
Deaths due to Pneumonia48 48 93 35 48 48
QALYs52 52 -283 45 -3 17
Life-years-389 -389 -1,061 -257 -389 -389
Costs (million $)
Total Cost-$5 -$3 -$4 $19 -$5 -$5
Medical Costs-$34 -$34 -$25 -$23 -$34 -$34
Vaccine Costs$75 $78 $75 $75 $75 $75
Work Loss-$47 -$47 -$54 -$33 -$47 -$47
Cost Ratios ($)
Cost/QALYCost -Saving Cost -Saving 15,489* 429,479 1,739,015* Cost -Saving
Cost/Life -year 13,675* 6,916* 4,138* Dominated 13,675* 13,675*Cohort of 50 -year -olds. Comparator is PCV21 at CMC/IC or age 65.
* Dollars saved per QALY or Life -year lost.
22Question 2 Modeling Strategies
❑“Moving age -based recommendation from 65 to 50”
▪Shifts disease burden from younger to older adults
▪Save the cost of vaccinating 65 -year -olds
❑“Adding vaccination at 50 in addition to 65”
▪Isolates disease burden reduction from 50– to 64 -year -olds
•Convenient since we assume 15 -year vaccine duration
▪Clinicians may be unwilling to not re -vaccinate at age 65 in above
recommendation
23Question 2: Vaccination at age 50 and 65
BasePCV21 @
$335.60PCV20 Child
Indirect 0%Serotype 4 @
30%Fix QALY
DecrementsTang QALY
Decrements
Health Outcomes
IPD Cases -424 -424 -560 -307 -424 -424
Hospitalized Pneumonia Cases -462 -462 -412 -306 -462 -462
Non -hospitalized Pneumonia
Cases-3,202 -3,202 -3,835 -2,184 -3,202 -3,202
Deaths due to IPD -41 -41 -53 -30 -41 -41
Deaths due to Pneumonia -8 -8 -3 -5 -8 -8
QALYs 1,105 1,105 1,408 780 1,096 1,074
Life-years 1,262 1,262 1,574 895 1,262 1,262
Costs (million $)
Total Cost $298 $317 $253 $344 298 $298
Medical Costs -$84 -$84 -$110 -$59 -84 -$84
Vaccine Costs $450 $468 $450 $450 450 $450
Work Loss -$67 -$67 -$87 -$47 -67 -$67
Cost Ratios ($)
Cost/QALY 269,932 286,553 179,685 440,518 272,038 277,778
Cost/Life -year 236,322 250,873 160,744 384,319 236,322 236,322Cohort of 50 -year -olds. Comparator is PCV21 at CMC/IC or age 65.
24Question 3: Vaccination at age 19
BasePCV21 @
$335.60PCV20 Child
Indirect 0%Serotype 4 @
30%Fix QALY
DecrementsTang QALY
Decrements
Health Outcomes
IPD Cases223 223 373 158 223 223
Hospitalized Pneumonia Cases350 350 564 244 350 350
Non -hospitalized Pneumonia
Cases926 926 1,649 659 926 926
Deaths due to IPD28 28 46 20 28 28
Deaths due to Pneumonia11 11 17 8 11 11
QALYs-507 -507 -835 -358 -509 -498
Life-years-682 -682 -1,113 -481 -682 -682
Costs (million $)
Total Cost$185 $190 $222 $168 $185 $185
Medical Costs$35 $35 $57 $25 $35 $35
Vaccine Costs$129 $134 $129 $129 $129 $129
Work Loss$21 $21 $35 $15 $21 $21
Cost Ratios ($)
Cost/QALYDominated Dominated Dominated Dominated Dominated Dominated
Cost/Life -year Dominated Dominated Dominated Dominated Dominated DominatedCohort of 19 -year -olds. Comparator is PCV21 at CMC/IC or age 50.
25Supplemental PCV21 One Year after PCV20 (all)
BasePCV21 @
$335.60PCV20 Child
Indirect 0%Serotype 4 @
30%Tang QALY
Decrements
Health Outcomes
IPD Cases-847 -847 -866 -525 -847
Hospitalized Pneumonia Cases-1,875 -1,875 -1,973 -1,276 -1,875
Non -hospitalized Pneumonia Cases
-3,981 -3,981 -4,065 -2,690 -3,981
Deaths due to IPD-104 -104 -107 -65 -104
Deaths due to Pneumonia-70 -70 -74 -48 -70
QALYs1,261 1,261 1,285 808 1,286
Life-years2,059 2,059 2,110 1,325 2,059
Costs (million $)
Total Cost$557 $584 $555 $587 $557
Medical Costs-$65 -$65 -$67 -$43 -$65
Vaccine Costs$644 $671 $644 $644 $644
Work Loss-$23 -$23 -$23 -$15 -$23
Cost Ratios ($)
Cost/QALY442,010 463,475 431,656 726,607 433,172
Cost/Life -year 270,614 283,756 262,879 443,207 270,614Cohort of 66 -year -olds. Comparator is no additional vaccine.
26Supplemental PCV21 Five Years after PCV20 (all)
BasePCV21 @
$335.60PCV20 Child
Indirect 0%Serotype 4 @
30%Tang QALY
Decrements
Health Outcomes
IPD Cases-1,035 -1,035 -1,300 -673 -1,035
Hospitalized Pneumonia Cases-3,360 -3,360 -4,852 -2,355 -3,360
Non -hospitalized Pneumonia Cases
-5,770 -5,770 -8,028 -4,015 -5,770
Deaths due to IPD-129 -129 -163 -84 -129
Deaths due to Pneumonia-132 -132 -193 -93 -132
QALYs1,580 1,580 2,099 1,064 1,600
Life-years2,608 2,608 3,460 1,757 2,608
Costs (million $)
Total Cost$485 $510 $439 $524 $485
Medical Costs-$102 -$102 -$142 -$70 -$102
Vaccine Costs$608 $634 $608 $608 $608
Work Loss-$22 -$22 -$28 -$15 -$22
Cost Ratios ($)
Cost/QALY306,901 323,076 209,103 492,194 302,891
Cost/Life -year 185,860 195,656 126,871 298,071 185,860Cohort of 70 -year -olds. Comparator is no additional vaccine.
27Supplemental PCV21 1/5 years after PCV20 Among Adults with CMC/IC
Comparator is no additional vaccine.
1 Year
Cohort @411 Year
Cohort @451 Year
Cohort @555 Years
Cohort @415 Years
Cohort @455 Years
Cohort @55
Health Outcomes
IPD Cases-508 -532 -514 -553 -580 -584
Hospitalized Pneumonia Cases-933 -990 -1,056 -1,049 -1,119 -1,239
Non -hospitalized Pneumonia
Cases-3,593 -3,504 -3,031 -3,903 -3,823 -3,448
Deaths due to IPD-57 -62 -63 -63 -68 -73
Deaths due to Pneumonia-29 -32 -37 -34 -37 -44
QALYs936 981 897 1,004 1,053 1,010
Life-years1,320 1,394 1,332 1,424 1,506 1,504
Costs (million $)
Total Cost$314 $291 $199 $314 $287 $208
Medical Costs-$66 -$68 -$61 -$71 -$73 -$69
Vaccine Costs$421 $399 $289 $428 $402 $309
Work Loss-$41 -$40 -$28 -$44 -$42 -$31
Cost Ratios ($)
Cost/QALY335,330 296,483 221,736 312,933 272,520 206,191
Cost/Life -year 237,779 208,572 149,339 220,664 190,605 138,491
28Alternate Efficiency Measures
(Does not account for overlap between measures)
Number needed to vaccinate to prevent…
PCV21
@65PCV21
@CMC/ICPCV21
@50 & @65PCV21 Suppl
@66PCV21 Suppl
@70
Hospitalization 643 572 7,127 512 300
Case 263 180 974 209 130
Death 9,758 9,026 155,708 8,087 5,109
PCV21
@65PCV21
@CMC/ICPCV21
@50 & @65PCV21 Suppl
@66PCV21 Suppl
@70
Hospitalization $2,227 Cost -Saving $335,952 $205,491 $111,219
Case $906 Cost -Saving $72,898 $83,279 $47,910
Death $33,521 Cost -Saving $6,139,249 $3,220,043 $1,879,564 $ per averted…
29Limitations
❑Sequelae from IPD not modeled explicitly
❑Ranges on serotype distributions and other IPD data from ABCs
are +/ - 25% by assumption
❑Uncertainties about the pneumococcal disease trends due to
pneumococcal serotypes that are no longer included in PCV21
(e.g., serotype 4, 19F)
❑Uncertainties about the indirect effects from pediatric PCV20 use
❑Disruption from changing pneumococcal schedule not modeled
❑Disease rates are constant within specified age bins as single -year
of age disease estimates are unlikely to be precise.
30Summary
❑ Replacing PCV20 with PCV21 at age 65 increases QAL Ys with modest increases in
cost
▪Simulations range from $4,000 to $28,000 / QALY in several scenarios
▪Replacing PCV20 with PCV21 is dominated (lower QALYs and more costs) in a scenario where
serotype 4 disease accounts for 30% of pneumococcal disease
❑ Replacing PCV20 with PCV21 at diagnosis of IC or CMC before age 65 is cost -saving
▪Cost is $110,000/QALY in a scenario where serotype 4 disease accounts for 30%
▪At serotype 4 disease rates at 35% or above it results in decreased QALYs
❑ Moving PCV21 vaccination from age 65 to age 50 increases case counts and deaths,
but also results in gains in QAL Ys
▪Disease burden is shifted from younger adults to older adults who have lower background
QALY values
❑ Vaccinating at both age 50 and age 65 costs $300,000/QAL Y
▪ Sensitivity analyses range from $200,000/QALY to $400,000/QALY
❑ Vaccinating with PCV21 at age 19 instead of age 50 is dominated
▪ Less health (both lower QALYs and more cases) and increased costs
❑ Supplemental PCV21 at age 65 that includes all adults that previously had PCV20
(at age 65 or at CMC/IC) costs $400,000/QAL Y
▪ If the supplemental dose is delayed until age 70 the cost drops to $300,000/QALY
❑ Supplemental PCV21 for the CMC/IC population ranges from $200,000 to $300,000
per QAL Y in the base case
▪ Cost per QALY is 5 -30% lower if PCV21 is delayed 5 years after PCV20 vaccination rather than 1 year afterward
▪ Assuming no herd immunity from childhood PCV20 program is associated with the lowest cost per QALYs
31Thank you!
Please send comments to:
[email protected]
Contributors:
Andrew Leidner
Miwako Kobayashi
Bo-Hyun Cho
Yin Wang
Cheryl Ward
National Center for Immunization & Respiratory Diseases
HSREB – Econ Team
32IPD Rates per 100k
Source: Active Bacterial Core Surveillance System, 2017 -2018; NHIS 2017 –2018. For multivariate sensitivity analyses distributio ns are beta -pert with -/+20% for
low and high. Risk Group19-49
Years50-64
Years65-74
Years75-84
Years85+
Years
General 2.09 6.09 8.25 13.90 33.06
CMC 8.09 24.04 25.89 33.34 58.57
IC 16.22 37.28 35.10 36.81 46.38
33NBP Hospitalization Rates per 100k
Source: MarketScan & Optum databases. 2013 -2015 data. (Pelton et al. CID 2019) (95% CIs in parenthesis)Risk
Group19-49
Years50-64
Years65-74
Years75+
Years
General 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) 3992 (3944, 4040)
34NBP Outpatient Rates per 100k
Source: Tong et al. 2014 data. BMC Health Serv Res 2018. For multivariate sensitivity analyses distributions are beta -pert with -/+20% f or low and high.Risk Group19-49
Years50-64
Years65-74
Years75-84
Years85+
Years
General 322.92 385.04 491.98 1366.22 2378.97
CMC 1872.91 1886.72 2410.70 3962.03 6899.00
IC 6361.40 5352.10 5461.00 5738.10 9991.70
35IPD Cases Resulting in Fatality
Source: Active Bacterial Core Surveillance System, 2017 -2018. For multivariate sensitivity analyses distributions are beta -pert with -/+20% for low and high.Risk Group19-49
Years50-64
Years65-74
Years75-84
Years85+
Years
General 5.54% 8.73% 7.93% 11.25% 17.30%
CMC 7.24% 11.06% 12.22% 12.82% 22.97%
IC 10.04% 14.27% 13.97% 11.33% 17.62%
36IPT NBP Cases Resulting in Fatality
Base Low High
18-49 Years 1.6 0.4 2.9
50-64 Years 2.8 1.1 4.4
65-74 Years 3.5 1.5 5.5
75-84 Years 4.1 2.2 6.0
85+ Years 5.3 3.3 7.2
Source: NIS2018 (lower bound: ICD -10 code J13 or J181 for primary diagnosis; upper bound: ICD -10 code J13 or J181 in ANY locatio n; base: mean of LB and UB).
Low and High parameters used in beta -pert distribution
37Vaccine Effectiveness
a. Bonten NEJM 2015 (per protocol)
b. Point estimate from Pilishvili et al. ISPPD2018 abstract, lower bound set to 0, upper bound from Lewis 2020 ISPPD poster
c. Suaya Vaccine 2018; 1477 -1483.
d. Applied the ratio of IPD VE/Pneumonia VE for all PCV13 types to the point estimate for ST3 IPD VE. General CMC IC
PCV vs VT ( -ST3) IPDa 75.0 (41.4, 90.8) 75.0 (41.4, 90.8) 25.0 (13.8, 30.3)
PCV vs ST3 IPDb 26.0 (0, 53.4) 26.0 (0, 53.4) 8.7 (0, 17.8)
PCV vs VT ( -ST3) NBPc 66.7 (11.8, 89.3) 40.3 (11.4, 60.2) 15.0 (4.7, 21.8)
PCV vs ST3 NBPd 15.6 (0, 32.0) 15.6 (0, 32.0) 5.2 (0, 10.7)
38Coverage Rates
Base Lowe Highe
PCV Age -based 19 -49a 22.2 17.76 26.64
PCV Age -based 50 -64b 39.65 23.3 56
PCV, Age -based 65+c 56 49 63
Risk -based (at development of CMC/IC)a 22.2 21 23.5
PCV21 supplemental dosed 40.7 11.2 63.4
a. NHIS 2021 data https://www.cdc.gov/vaccines/imz -managers/coverage/adultvaxview/pubs -resources/vaccination -coverage -adults -2021.html ; Low and
high in age -based 19 -49 context are -/+20% of base case; low and high in risk -based context are bounds of the 95% CI for coverag e among individuals
eligible for risk -based vaccination
b. Low: NHIS 2021 for Zoster Vaccine in adults 60 -64 years; high: base estimate for PCV15/PCV20 coverage in adults 65 years and old er; base: mean
c. High: NHIS 2021 any pneumococcal coverage; low: any PCV13 coverage data in Medicare beneficiaries aged ≥65 years, 2019; base: mean
d. % of PCV20 recipients who received PCV13 among Medicare Parts A/B beneficiaries as of Jan 17, 2024; low: coverage at age 66 y ears; high: coverage at
age 80 -84 years
e. Parameters for beta -pert distribution
39Herd Effects from 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 PCV20
❑Run versions of the model with and without these herd
effects to assess importance
Year Base Lower Upper
1 0.755161 0.707483 0.813869
2 0.496227 0.459737 0.53535
3 0.339094 0.312705 0.372755
4 0.244074 0.220786 0.268572
5 0.187125 0.166702 0.206661
6 0.156599 0.138492 0.177142
7+ No further declinesRemaining Share of Disease
Source: Unpublished CDC model.
40Utility Decrements
Variable QAL Y DecrementsaImplied Healthy Days
Lostb
IPD0.0709
(0.0509, 0.0909)25.9
IPT NBP0.0709
(0.0509, 0.0909)25.9
OPT NBP0.0045
(0.00399, 0.00501)1.6
a QALY values from Mangen et al. 2015 Eur Respir J (95% CIs in parenthesis)
b Health days lost were include on this slide to illustrate in relatable terms the magnitude of health loss associated with QAL Y decrements. Healthy days lost
calculated by multiplying QALY decrement by 365.
c Alternate values are inverse variance weighted values from Tang et al. 2021 J Pub Health. Source material places higher decre ment on outpatient disease
than inpatient disease for age 65+.Pneumococcal Disease
Treatment Intensity, AgeQALY
Decrement
Outpatient, 19 -64 0.0094
Inpatient, 19 -64 0.0396
Outpatient, 65+ 0.0586
Inpatient, 65+ 0.0087Alternate Utility Decrementsc
41Baseline QAL Y Values
Age General CMC/IC
50-55 0.83 (0.78,0.88) 0.72 (0.67,0.77)
56-60 0.81 (0.76,0.86) 0.69 (0.64,0.74)
61-65 0.77 (0.72,0.82) 0.63 (0.58,0.68)
66-70 0.76 (0.71,0.81) 0.57 (0.52,0.62)
71-75 0.74 (0.69,0.79) 0.54 (0.49,0.59)
76-80 0.7 (0.65,0.75) 0.52 (0.47,0.57)
81-85 0.63 (0.58,0.68) 0.51 (0.46,0.56)
86+ 0.51 (0.46,0.56) 0.51 (0.46,0.56)
Sisk, 2003.
42Disease Cost (2023$)
Data for ages 19 -64 from MarketScan 2019 -2022. Data for 65+ from CMS Medicare claims 2019 -2022. 95% CI from bootstrapping mean values with 1,000
iterations. All costs converted to 2023$ using CPI Medical Care before bootstrapping. See appendix slide for ICD -10 codes.Disease Setting Cost 95% CI
19-64 YearsIPD IPT $64,018.10 $61,559.31 $66,424.61
NBP IPT $58,423.99 $55,923.53 $60,908.13
NBP OPT $362.38 $339.44 $385.24
65+ YearsIPD IPT $27,564.22 $27,039.18 $28,149.20
NBP IPT $21,300.64 $20,825.64 $21,800.98
NBP OPT $318.22 $308.06 $328.70
43ICD -10 Codes for Medical Cost Extraction
Disease ICD-10 Codes
IPD A40.3, A40.9+B95.3, A41.9+B95.3, R78.81+B95.3, G00.1, G00.2+B95.3,
G00.9+B95.3, G03.9+B95.3, J86.x+B95.3, J85.1+B95.3, A40.3 + at least one code
from "All -cause", A40.9+B95.3 + at least one code from "All -cause",
A41.9+B95.3 + at least one code from "All -cause", R78.81+B95.3 + at least one
code from "All -cause", A40.9 & J13, A41.9 & J13, R78.81 & J13, M00.1x,
K65.8+B95.3, I30.1+B95.3, I33.0+B95.3, I33.9 +B95.3, K65.2+B95.3,
M86.1x/M86.2x/M86.9+B95.3, M00.0x, M00.2x, M00.8x, M00.9 + B95.3
NBP J13, J15.9+B95.3, J18.0/J18.1+B95.3, J18.8/J18.9+B95.3
All-cause (for
satisfying some
definitions of
IPD)J12.x (J12.0, J12.1, J12.2, J12.3, J12.81, J12.89, J12.9), J13, J18.1, A48.1, J14, J15.0,
J15.1, J15.2x (J15.20, J15.211, J15.212, J15.29), J15.3, J15.4, J15.5, J15.6, J15.8,
J15.9, J15.7, J16.x (J16.0, J16.8), A22.1, A37.X1, B25.0, B44.0, J17, J18.0, J18.2,
J18.8, J18.9, J09.X1, J10.0x (J10.00, J10.01, J10.08), J11.0x (J11.00, J11.08)
44Work Loss
AgeLabor Force
Participation
Rate (%)aMedian Daily
Wage ($)b
19 to 24 71 99.71
25 to 34 83.2 148.86
35 to 44 83 175.57
45 to 54 81.1 176.14
55 to 64 65.2 169.43
65 to 74 26.6 157.29
75+ 8.2 157.29
a US Bureau of Labor Statistics.
b Current Population Survey, 2023.
c Altawalbeh SM, Wateska AR, Nowalk MP, Lin CJ, Harrison LH, Schaffner W, Zimmerman RK, Smith KJ. Societal cost of racial pneumococcal disease disparities in
US adults aged 50 years or older. Applied Health Economics and Health Policy. 2024 Jan;22(1):61 -71.
d Used ratio of days of work loss from outpatient (14) to inpatient pneumonia (18) allowed by Marine Corps policy and applied t o inpatient durations of illness
from Altawalbeh 2024. Vold Pepper P, Owens DK. Cost -effectiveness of the pneumococcal vaccine in the United States Navy and Marine Corps. Clinical
infectious diseases. 2000 Jan 1;30(1):157 -64.Base High Low
Inpatientc 34 17 51
Outpatientd 26.4 13.2 39.7Labor Force Participation and Daily Wage Duration of Work Loss
45Question 1a: Vaccination at age 65 with PCV21
Serotype 4
@ 5%Serotype 4
@ 10%Serotype 4
@ 15%Serotype 4
@ 20%Serotype 4
@ 25%Serotype 4
@ 30%Serotype 4
@ 35+%
Health Outcomes
IPD Cases -749 -569 -389 -209 -28 152
Hospitalized Pneumonia Cases -1,498 -1,282 -1,067 -852 -637 -422
Non -hospitalized Pneumonia
Cases-3,350 -2,841 -2,333 -1,824 -1,316 -807
Deaths due to IPD -91 -69 -47 -25 -4 18
Deaths due to Pneumonia -55 -47 -39 -32 -24 -16
QALYs 1,132 897 661 426 191 -45
Life-years 1,808 1,431 1,055 679 302 -74
Costs (million $)
Total Cost 15 29 43 57 71 85
Medical Costs -54 -44 -34 -24 -15 -5
Vaccine Costs 90 90 90 90 90 90
Work Loss -21 -17 -12 -8 -4 1
Cost Ratios ($)
Cost/QALY 13,436 32,640 65,513 134,710 374,763 Dominated Dominated
Cost/Life -year 8,412 20,443 41,059 84,543 236,327 Dominated DominatedCohort of 65 -year -olds. Comparator is PCV20 at age 65.
Base case serotype 4 distributions are age, risk, and disease condition specific as displayed earlier in the slides. They ra nge from 0 to 9.99%