Cost-effectiveness of implementing 13-valent pneumococcal conjugate vaccine for U.S. adults aged 19 years and older with underlying conditions

Figures & data

Table

All-cause Pneumonia	Age groups
	19–44 years		45–64 years		65–74 years		75–84 years		≥85 years
	Value	95% CI	Value	95% CI	Value	95% CI	Value	95% CI	Value	95% CI
Inpatient All-cause Pneumonia Rate (per 100,000)^c	200.25	(150.0; 250.5)	579.85	(469.7; 690.0)	1216.10	(792.8; 1639.4)	2233.20	(2067.7; 2398.7)	3182.9	(2067.7; 4298.1)
Case fatality ratio (%)^d	2.4	(0.8; 3.9)	3.2	(1.2; 5.1)	3.7	(1.3; 6.1)	4.7	(2.1; 7.4)	7.2	(4.9; 9.4)
Outpatient All-cause Pneumonia rate (per 100,000)^e	736.2		893.9		1338.1		2186.6		3165.7
PCV13 type (%)^f	5.3	(3.1; 7.5)	5.3	(3.1; 7.5)	5.1	(3.4; 6.8)	5.1	(3.4; 6.8)	5.1	(3.4; 6.8)

^cThe lower bound of all-cause pneumonia for all age groups come from Jain et al.¹⁸ The upper bounds for 19–64 year old age groups come from Hayes et al.¹⁹ The upper bounds for age groups ≥65 years come from Ramirez et al.²⁰ CMC specific rates were estimated using the ratio of disease among different risk groups described in Weycker et al²¹weighted by the prevalence of different population of the risk groups estimated from NHIS data/To obtain the base case we take the midpoint between the upper bound and lower bound.

^dSource: National Inpatient Sample 2015. The upper bound is the fatality rate for cases with ICD-9 code with 481 in any location. The lower bound is for cases with ICD-9 code 481 for primary location. The base case is the midpoint of these two bounds.

^eSource: Nelson et al.²²

^fSource: Isturiz et al.²³ Base case estimate for 19–64 year olds are from Oct 2015–2016 estimate for at-risk group. Since the %PCV13 type for the three observed years were essentially the same for this age group, we used the Oct 2015–2016 estimate for the low-risk group as the lower bound. Upper bound is created for the range to be symmetrical around the base value. Since risk-group specific values were not presented for adults aged ≥65 years, we used Oct 2013–Sept 2014 value as the base case estimate for this age group. For the lower bound, we use the estimate for Oct 2015–Sept 2016. Upper bound is created to be symmetrical around the base value.

Table

		Age groups
Vaccine effectiveness		19–64 years		≥65 years
Vaccine type	Outcome	Value	Range	Value	Range
PCV13	PCV13-type IPD (-ST3, +ST6C)^g	75	(41.4; 90.8)	67	(11; 88)
PCV13	ST3 IPD^h	0	(0; 45)	0	(0; 26)
PCV13	PCV13-type NBPP (-ST3)^i	45	(14.2; 65.3)	32.5	(3.9; 53)
PCV13	ST3 NBPP^j	0	(0; 45)	0	(0; 45)
PPSV23	PPSV23-type IPD^k	73	(56.0; 84.0)	67	(37; 73)
PPSV23	PPSV23-type NBPP^l	0	(0; 50)	0	(0; 50)

^gSource: Bonten et al.²⁴ for 19–64 year old. Pilishvili et al for age ≥65 years²⁵

^hSource for adults aged ≥65 years from Pilishvili et al.²⁵ For adults aged 19–64 year olds, we assumed that the upper range will be as high as what we estimated for ST3 NBPP.

ⁱSource: Bonten et al. for age 19–64 years²⁴ Suaya et al.²⁶

^jWe assume PCV13 ineffective against ST3 pneumonia based on results from serotype 3 IPD.²⁵ For the upper bound of effectiveness, we use the effectiveness of PCV13 against all vaccine-type pneumonia from Bonten et al.²⁴

^kSource: Falkenhorst et al.²⁷ For 19–64 year olds, pooled estimate from case-control studies was used. For ≥65 years old, we assumed the point estimate to be the same as PCV13.

^lSource: Schiffner-Rohe, Falkenhorst, Tin Tin Htar.^27–29

Table

	Age groups
	19–64 years		≥65 years
Vaccine coverage	Value	Range	Value	Range
PCV13 Coverage Rate (%)^m	24.5	(23; 26)	47.1	(46.4; 50.7)
PPSV23 Coverage Rate (%)^n	24.5	(23; 26)	61.3	(59.9; 62.7)

^mFor age 19–64 year olds, we assumed that PCV13 coverage will be as high as PPSV23 coverage. For adults aged ≥65 years, the lower bound is from Centers for Medicare and Medicaid Services data and the upper bound is from Pfizer IQVIA Claims data. The base case is the midpoint.

ⁿSource for 19–64-year-olds was National Health Interview Survey, 2017.³⁰ Source for adults aged ≥65 years was National Health Interview Survey 2014.³¹

Table

	Age groups
	19–64 years		≥65 years
Cost per Case, 2017$^o	Value	95% CI	Value	95% CI
IPD	45,146	(35,915; 55,178)	30,459	(24,709; 36,753)
Inpatient NBPP	39,285	(28,628; 51,841)	26,187	(19,015; 35,630)
Outpatient NBPP	143	(86; 246)	285	(136; 519)

^oSource: CMS Medicare Claims from 2010–2015 inflated by Consumer Price Index for all items to 2017$.

Table

Cost associated with vaccination, 2017$	Value
PCV13^p	192.64
PPSV23^p	98.85
Vaccine administration cost per vaccination^q	26.61
Patient time and travel cost per vaccination^r	30.12

CI: confidence interval; CMC: chronic medical condition (chronic heart disease, chronic lung disease, diabetes, alcohol abuse, or chronic liver disease); IPD: invasive pneumococcal disease; NBPP: non-bacteremic pneumococcal pneumonia; PCV13: 13-valent pneumococcal conjugate vaccine; PPSV11: 11 serotypes unique to PPSV23 but not in PCV13 (STs 2, 8, 9 N, 10A, 11A, 12 F, 15B, 17 F, 20, 22 F, 33 F); PPSV23: 23-valent pneumococcal polysaccharide vaccine; ST: serotype

^p95% of the average wholesale price as reported by Medicare Part B, December 2017.

^qEstimated from the Medicare reimbursement for immunization administration (HCPCS code 90471) in 2017 averaged across all Medicare Administrative Contractors

^rSource: Maciosek et al.⁵² inflated by Consumer Price Index for all items to 2017$.

Table 1. Model input parameters for U.S. adults with chronic medical conditions, by age group

	Age groups
	19–64 years		≥65 years
IPD^a	Value	95% CI	Value	95% CI
Rate (per 100,000 population)	16.25	(15.27; 17.29)	40.89	(38.17; 43.80)
Case fatality ratio (%)	12.40%		15.71%
PCV13 (+6 C-3-19 F) type (%)^b	11.80%		7.20%
ST3 (%)	14.74%		16.22%
ST19F (%)	3.00%		1.90%
PPSV11 (%)	43.66%		38.41%

^aSource: ABCs data 2016–2017. Note inputs from ABCs are displayed here for reproducibility of final results. The number of digits displayed should not necessarily be construed as a measure of accuracy of these outputs from ABCs data. Population denominators to construct rates come from NHIS.

^bWe group serotype 6 C with PCV13 types due to cross-reactivity with serotype 6A. We treat serotypes 3 and 19 F separately due to observed performance in ABCs data.

Table 2. Impact of adding PCV13 at diagnosis of chronic medical conditions, base case

	No PCV13 (A)	Adding PCV13 (B)	Base Case (B)-(A)	(5^th percentile; 95^th percentile)
Health Outcomes
IPD Cases	9,121	9,068	−54	(−77; −37)
Hospitalized NBPP Cases	144,896	144,577	−319	(−1,063; −216)
Non-hospitalized NBPP Cases	200,824	200,258	−565	(−1,678; −381)
Deaths due to IPD	880	876	−4	(−6; −3)
Deaths due to NBPP	5,304	5,293	−10	(−37; −6)
Discounted QALYs gained	−53,314	−53,141	174	(176; 614)
Discounted life-years gained	−83,087	−82,831	255	(198; 646)
Costs (million $)
Total Cost	3,426	3,546	$120	(99; 124)
Medical Costs	3,254	3,243	-$11	(−31; −9)
Vaccine Costs	172	303	$131	(126; 135)
Cost Ratios ($)
Cost/QALY	–	–	689,299	(165,232; 686,856)
Cost/Life-year	–	–	468,449	(156,621; 611,947)

IPD: invasive pneumococcal disease; NBPP: non-bacteremic pneumococcal pneumonia; QALY: quality-adjusted life year

Table 3. Impact of adding PCV13 at diagnosis of chronic medical conditions, one-way sensitivity analyses

	PCV13 VE vs ST3 IPD Equal to Protection Against other Serotypes of IPD^a	PCV13 VE vs ST3 NBPP Equal to Protection Against other Serotypes of NBPP^a	PCV13 VE vs ST3 NBPP and IPD Equal to Protection Against other Serotypes of Disease^a
Health Outcomes
IPD Cases	−141	−54	−141
Hospitalized NBPP Cases	−319	−2,244	−2,244
Non-hospitalized NBPP Cases	−565	−3,427	−3,427
Deaths due to IPD	−12	−4	−12
Deaths due to NBPP	−10	−77	−77
Discounted QALYs gained	269	809	904
Discounted life-years gained	393	1,243	1,382
Costs (million $)
Total Cost	$116	$75	$72
Medical Costs	-$15	-$55	-$59
Vaccine Costs	$131	$131	$131
Cost Ratios ($)
Cost/QALY	431,419	93,184	79,416
Cost/Life-year	294,922	60,616	51,981

IPD: invasive pneumococcal disease; NBPP: non-bacteremic pneumococcal pneumonia; PCV13: 13-valent pneumococcal conjugate vaccine; QALY: quality-adjusted life year; ST: serotype

^aWhen PCV13 is assigned equal VE against ST3 disease as against other serotypes it is assigned 75% vs IPD and 45% vs NBPP for the 19–64 age group and 67% vs IPD and 32.5% vs NBPP for the 65+ age group

Figure 1. Tornado diagram of model sensitivity to outputs

CMC: chronic medical condition (chronic heart disease, chronic lung disease, diabetes, alcohol abuse, or chronic liver disease); IPT: inpatient; PCV13: 13-valent pneumococcal conjugate vaccine; pneumonia: non-bacteremic pneumococcal pneumonia; PPSV23: 23-valent pneumococcal polysaccharide vaccine; QALY: quality-adjusted life year; ST: serotype

Jain S, Self WH, Wunderink RG, Fakhran S, Balk R, Bramley AM, Reed C, Grijalva CG, Anderson EJ, Courtney DM, et al. Community-Acquired Pneumonia Requiring Hospitalization among U.S. Adults. N Engl J Med. 2015;373(5):415–27. doi:10.1056/NEJMoa1500245.

 PubMed Web of Science ®Google Scholar

Hayes BH, Haberling DL, Kennedy JL, Varma JK, Fry AM, Vora NM. Burden of Pneumonia-Associated Hospitalizations: united States, 2001-2014. Chest. 2018;153(2):427–37. doi:10.1016/j.chest.2017.09.041.

 PubMed Web of Science ®Google Scholar

Ramirez JA, Wiemken TL, Peyrani P, Arnold FW, Kelley R, Mattingly WA, Nakamatsu R, Pena S, Guinn BE, Furmanek SP, et al. Adults Hospitalized With Pneumonia in the United States: incidence, Epidemiology, and Mortality. Clinical infectious diseases: an official publication of the Infectious Diseases Society of America. 2017;65(11):1806–12. doi:10.1093/cid/cix647.

 PubMed Web of Science ®Google Scholar

Weycker D, Farkouh RA, Strutton DR, Edelsberg J, Shea KM, Pelton SI. Rates and costs of invasive pneumococcal disease and pneumonia in persons with underlying medical conditions. BMC Health Serv Res. 2016;16(1):182. doi:10.1186/s12913-016-1432-4.

 PubMed Web of Science ®Google Scholar

Nelson JC, Jackson M, Yua O, Whitney CG, Bounds L, Bittner R, Zavitkovsky A, Jackson LA. Impact of the Introduction of Pneumococcal Conjugate Vaccine on Rates of Community Acquired Pneumonia in Children and Adults. Vaccine. 2008;26(38):4947–54. doi:10.1016/j.vaccine.2008.07.016.

 PubMed Web of Science ®Google Scholar

Isturiz RE, Ramirez J, Self WH, Grijalva CG, Counselman FL, Volturo G, Ostrosky-Zeichner L, Peyrani P, Wunderink RG, Sherwin R, et al. Pneumococcal epidemiology among us adults hospitalized for community-acquired pneumonia. Vaccine. 2019;37(25):3352–61. doi:10.1016/j.vaccine.2019.04.087.

 PubMed Web of Science ®Google Scholar

Bonten MJ, Huijts SM, Bolkenbaas M, Webber C, Patterson S, Gault S, van Werkhoven CH, van Deursen AMM, Sanders EAM, Verheij TJM, et al. Polysaccharide conjugate vaccine against pneumococcal pneumonia in adults. N Engl J Med. 2015;372(12):1114–25. doi:10.1056/NEJMoa1408544.

 PubMed Web of Science ®Google Scholar

Pilishvili T, Almendares O, Nanduri S, Warnock R, Wu X, McKean S, Kelman J, Farley M, Schaffner W, Thomas A, et al. Case-Control Study to Evaluate Pneumococcal Vaccines Effectiveness against Invasive Pneumococcal Disease (IPD) Among U.S. Medicare Beneficiaries ≥65 Years Old. ISPPD Abstract 0682 2018.

 Google Scholar

Suaya JA, Jiang Q, Scott DA, Gruber WC, Webber C, Schmoele-Thoma B, Hall-Murray CK, Jodar L, Isturiz RE. Post Hoc Analysis of the Efficacy of the 13-Valent Pneumococcal Conjugate Vaccine against Vaccine-type Community-acquired Pneumonia in at-risk Older Adults. Vaccine. 2018;36(11):1477–83. doi:10.1016/j.vaccine.2018.01.049.

 PubMed Web of Science ®Google Scholar

Falkenhorst G, Remschmidt C, Harder T, Hummers-Pradier E, Wichmann O, Bogdan C, Ho PL. Effectiveness of the 23-Valent Pneumococcal Polysaccharide Vaccine (PPV23) against Pneumococcal Disease in the Elderly: systematic Review and Meta-Analysis. PloS One. 2017;12(1):e0169368. doi:10.1371/journal.pone.0169368.

 PubMed Web of Science ®Google Scholar

Hung M-C, Williams WW, Lu P-J, Woods LO, Koppaka R, Lidley MC Vaccination Coverage among Adults in the United States, National Health Interview Survey, 2017, 2018.

 Google Scholar

Williams WW, Lu PJ, O’Halloran A, Kim DK, Grohskopf LA, Pilishvili T, Skoff TH, Nelson NP, Harpaz R, Markowitz LE, et al. Surveillance of Vaccination Coverage Among Adult Populations - United States, 2014. Morbidity and mortality weekly report Surveillance summaries (Washington, DC: 2002) 2016; 65:1–36.

 Google Scholar

Maciosek MV, Solberg LI, Coffield AB, Edwards NM, Goodman MJ. Influenza vaccination health impact and cost effectiveness among adults aged 50 to 64 and 65 and older. Am J Prev Med. 2006;31(1):72–79. doi:10.1016/j.amepre.2006.03.008.

 PubMed Web of Science ®Google Scholar