Age, revaccination, and tolerance effects on pneumococcal vaccination strategies in the elderly: A cost-effectiveness analysis

Vaccine 27 (2009) 3159–3164

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Age, revaccination, and tolerance effects on pneumococcal vaccination strategies in the elderly: A cost-effectiveness analysis Kenneth J. Smith a,∗ , Richard K. Zimmerman b,c , Mary Patricia Nowalk b , Mark S. Roberts a,d,e a

Section of Decision Sciences and Clinical Systems Modeling, University of Pittsburgh, Pittsburgh, PA, USA Department of Family Medicine and Clinical Epidemiology, University of Pittsburgh, Pittsburgh, PA, USA School of Medicine, Department of Behavioral and Community Health Sciences, University of Pittsburgh, Pittsburgh, PA, USA d Department of Health Policy and Management, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA e Department of Industrial Engineering, University of Pittsburgh, Pittsburgh, PA, USA b c

a r t i c l e

i n f o

Article history: Received 10 October 2008 Received in revised form 16 March 2009 Accepted 23 March 2009 Available online 9 April 2009 Keywords: Pneumococcal vaccines Pneumococcal infections Cost-effectiveness analysis

a b s t r a c t Optimal pneumococcal polysaccharide vaccination (PPV) policy is unknown for cohorts aged ≥65 years. Using a Markov model, we estimated the cost-effectiveness of single- and multiple-dose PPV strategies in 65-, 75-, and 80-year-old cohorts. PPV at age 65 cost $26,100 per QALY (quality adjusted life years) gained. Vaccination at ages 75 and 80 cost $71,300–75,800 per QALY; revaccination strategies cost more. When prior vaccination and loss of vaccine effectiveness due to tolerance are assumed, cost-effectiveness ratios increase substantially. Single-dose PPV is worth considering in patients aged 65–80 from clinical and economic standpoints. Revaccination strategies for the elderly are less cost-effective, particularly when prior vaccination and vaccine tolerance are considered. © 2009 Elsevier Ltd. All rights reserved.

1. Introduction Pneumococcal polysaccharide vaccination (PPV) prevents invasive pneumococcal disease (IPD), a major cause of morbidity and mortality in the US, particularly in the elderly [1]. Under present recommendations for PPV, most adults would receive PPV at age 65 unless a comorbid condition that increases IPD risk was diagnosed before age 65, in which case PPV would be performed when the comorbid condition was diagnosed with a second vaccination given at age 65 or thereafter [1]. Questions have arisen about the appropriateness of these recommendations [2], due to the incidence of IPD at not insignificant rates in persons without a present indication for PPV, the waning of immunity after PPV, and the demonstrated safety of repeated PPV [3–7]. We and others have performed analyses examining PPV strategies, finding that vaccinating at age 50, rather than at 65, is clinically and economically reasonable [8], and that multiple PPV doses, starting at age 50 and separated by 10–15 years, provide greater protection from IPD than single-dose PPV strategies at economically manageable cost-effectiveness ratios [9]. This information suggests that multiple PPV doses, now recommended only

∗ Corresponding author at: Section of Decision Sciences and Clinical Systems Modeling, University of Pittsburgh, 200 Meyran Ave, Suite 200, Pittsburgh, PA 15213, USA. Tel.: +1 412 647 4794; fax: +1 412 246 6954. E-mail address: [email protected] (K.J. Smith). 0264-410X/$ – see front matter © 2009 Elsevier Ltd. All rights reserved. doi:10.1016/j.vaccine.2009.03.059

for persons with comorbid conditions, should be more widely considered. However, these analyses were limited to 50-year-old cohorts, and therefore cannot answer questions regarding the optimal approach for people already 65 or older. These questions are particularly important for this patient group, since their IPD risk is higher [1,10]. In addition, it is unlikely that PPV will be recommended for younger age groups, and the optimal vaccination strategy for 65-year olds, the present recommended age for most US adults to receive PPV, is unknown. The purpose of this analysis is to estimate the cost-effectiveness of single and multiple-dose PPV regimens for present day 65-, 75-, and 80-year-old patients, an area where optimal vaccination practice is unclear, particularly when IPD epidemiology is changing due to the herd immunity effects of childhood pneumococcal conjugate vaccination [10]. 2. Methods We used a Markov model to estimate, in separate analyses of hypothetical patient cohorts aged 65-, 75-, and 80-year olds, the cost-effectiveness of single-dose and multiple-dose PPV strategies. In the analysis, costs were in 2003 US$ and effectiveness was measured using quality adjusted life years (QALY), the product of the years of life lived in a given health state and the quality of life utility for that state summed over time. Both costs and effectiveness were discounted at 3% per year, and the analysis took a societal perspective; in these and in other features of the analysis we followed the

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Fig. 1. The Markov model.

reference case recommendations of the panel on cost-effectiveness in health and medicine [11]. A key assumption of the model is that PPV has no efficacy against noninvasive pneumococcal pneumonia but is effective against IPD [12]. If PPV is efficacious against noninvasive pneumococcal pneumonia, as some studies suggest [13], then our model results will be biased against vaccination. The Markov model is shown schematically in Fig. 1. In each age cohort, patients could start the model in either a susceptible or vaccinated state, based on the probability of vaccination and vaccine protection and, in either an average risk or high risk state, on the age-related likelihood of comorbid illness. For the high risk states (not shown in the diagram), we separately modeled immunocompromising conditions (HIV infection, Hodgkin disease, leukemia, myeloma, dialysis, nephrotic syndrome, solid organ or bone marrow transplant, immunoglobulin deficiency, asplenia, sickle cell disease, or current immunosuppressive therapy) and other comorbid conditions (congestive heart failure, cardiomyopathy, atherosclerotic cardiovascular disease, chronic obstructive pulmonary disease, diabetes, cirrhosis, cerebrospinal fluid leak, or alcohol abuse), as defined by the Centers for Disease Control and Prevention (CDC) [10]. Based

on the age- and comorbidity-specific IPD rates and the likelihood of vaccine protection, patients in these states could become ill due to IPD. Patients with IPD could recover, or become disabled or die due to IPD. Patients could also die due to other causes at rates based on US mortality tables. The Markov cycle length of the model was 1 month, and the model cycled until all cohort members died. In 65-year olds, 10 vaccination strategies were examined: no vaccination, one vaccination, two vaccinations (ages 65 and 70, 65 and 75, 65 and 80, 65 and 85), three vaccinations (ages 65, 70, and 75; ages 65, 71, and 77; ages 65, 75, and 85), and four vaccinations (ages 65, 70, 75, and 80). In the 75-year-old cohort, four strategies were evaluated: no vaccination, one vaccination, vaccination at ages 75 and 80, or at 75 and 85. Strategies examined in 80-year-old cohorts were no vaccination, one vaccination, and two vaccinations at ages 80 and 85. The data sources used in the model have been previously described [9]. Briefly, we used National Health Interview Survey data from 2003 to 2004 to stratify cohorts into groups with no comorbidities, immunocompromising conditions, or other comorbid conditions. In addition, Framingham study and surveillance, epidemiology and end results (SEER) program data were used to model age-related comorbidity incidence and mortality in the oldest age groups [14–18]. Age- and comorbidity-specific IPD incidence and mortality data were obtained using 2003–2004 active bacterial core surveillance (ABCs) data from the CDC (Table 1). This data includes the effects of childhood pneumococcal conjugate vaccination, which was licensed for use in the US in 2000 [10]. IPD-related meningitis rates were used as a proxy for IPD-related disability incidence. IPD rates were adjusted, using CDC methods, to produce IPD rates that would be expected if no vaccination existed [19]. It should be noted that, based on 2003–2004 ABCs data, IPD rates in patients with immunocompromising conditions are higher than for average risk persons and may be higher or lower compared to patients with other comorbid conditions. Vaccine serotype coverage data also came from the ABCs (Table 1). Expert panel estimates of age-, comorbidity-, and duration-specific protection from IPD were used to calculate the likelihood of IPD prevention for cohorts over time (Table 2). Vaccine protection for persons vaccinated at ages other than 65 and 80 were estimated using linear interpolation from the expert panel estimates. Vaccine adverse event data, including the increased likelihood of such events with repeat vaccination, and quality of life utility weights were obtained from the literature [6–8]. Costs related to vaccination and vaccination adverse events were also obtained from the literature [8,20–22]; Healthcare Cost and Utilization Project (HCUP) data from 2003 were used

Table 1 Characteristics of invasive pneumococcal infections based on the active bacterial core surveillance systema . Age 65–69

Age ≥85

Age 70–74

Age 75–79

Age 80–84

26.2

31.8

37.0

48.9

73.2

10.8 53.2 58.0

17.0 56.2 48.0

17.8 60.3 53.0

21.9 97.3 49.1

44.8 126.2 51.5

1.3 3.9

1.5 5.4

1.1 6.8

1.5 11.2

0.8 19.5

76.6%

73.3%

75.9%

70.7%

70.4%

79.8% 74.1% 74.4%

75.9% 71.2% 69.6%

82.9% 74.2% 71.8%

78.9% 69.6% 57.5%

74.6% 69.6% 64.9%

Invasive pneumococcal disease rates (per 100,000 population per year) Total No comorbid or immunocompromising conditions ≥1 comorbid conditions ≥1 immunocompromising conditions Disease outcome rates (per 100,000 population per year) Meningitis Mortality PPV vaccine serotype coverage (%) Total No comorbid or immunocompromising conditions ≥1 comorbid conditions ≥1 immunocompromising conditions a

Source: Active Bacterial Core Surveillance 2003–04, Centers for Disease Control and Prevention.

K.J. Smith et al. / Vaccine 27 (2009) 3159–3164

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Table 2 Expert panel estimates of PPV effectiveness (%) in preventing vaccine-susceptible invasive pneumococcal disease. Vaccinee age/health

Healthy 65-year oldsa Base case

Years post-vaccination 1 3 5 7 10 15 a

80 73 58 33 0 0

Healthy 80-year oldsa

Range

Base case

Low

High

60 50 30.5 13 0 0

90 83 80 48 10 10

67 53 32 10 0 0

Immunocompromised (all ages)

Range

Base case

Low

High

20 0 0 0 0 0

85 83.5 75 30 10 10

0 0 0 0 0 0

Range Low

High

0 0 0 0 0 0

25.5 18 5 5 2.5 2.5

Patients with other comorbid conditions vaccinated at these ages had the same base case and high range values, low range was decreased 25% relative to listed values.

to estimate IPD costs [23]. Parameter values used in the model are summarized in Table 3. In the base case analysis, we assumed that patients had not previously received PPV. Thus, this analysis examines, in 75- and 80year olds, the subgroup of patients in these age groups that had not been previously vaccinated. In a separate analysis, we also examine the combined effects of prior vaccination and the development of vaccine tolerance, where we assume that subsequent vaccinations are 20% less protective than the first vaccination, based on expert panel recommendations for sensitivity analysis. We assumed that prior vaccinations had no carryover effects after subsequent vac-

cinations and, in tolerance scenarios, that subsequent vaccinations had attenuated effectiveness compared to persons of that age who had not been previously vaccinated. In addition, all parameter values were varied individually in one-way sensitivity analyses and all parameters were varied simultaneously over distributions 3000 times in a probabilistic sensitivity analysis as described previously [9]. Parameters whose distributions were least certain (utility and disability related parameters) were varied over uniform distributions, where values in the range are equally likely to be chosen. Expert panel estimates of vaccine effectiveness were varied over triangular distributions, and parameters derived from clinical trial

Table 3 Parameter values and ranges examined in sensitivity analyses. Description

Base case

Range

Source

Low

High

Vaccine effectiveness Relative risk of infection with vaccine serotypes

Base 1

Low range 0.9

High range 1.1

Expert panel Table 1

Vaccine adverse events Duration of symptoms (days) Probability per vaccinee after first vaccination Relative risk after subsequent vaccinations

3 3.2% 3.3

1 2.2% 2.1

8 4.6% 5.1

[7] [7] [7]

Disability Excess mortality per year Relative risk

0.1 1

0 0.5

1 1.5

Estimated Table 1a

1.5

1.3

1.8

[10] [8]

Average risk population 65–70 years 70–75 years 75–80 years 80–85 years >85 years

0.76 0.74 0.7 0.63 0.51

0.71 0.69 0.65 0.58 0.46

0.81 0.79 0.75 0.68 0.56

High risk population 65–70 years 70–75 years 75–80 years 80–85 years >85 years

0.57 0.54 0.52 0.51 0.51

0.52 0.49 0.47 0.46 0.46

0.62 0.59 0.57 0.56 0.56

0.2 0.4 0.9

0.1 0.2 0.8

0.5 0.6 0.99

[8] Estimate [36] Estimate [36]

$30

$15

$50

[8,20–22] [23]

Discharged alive 65–74 >74

$9351 $8326

Base Base

Base Base

Died 65–74 >74

$18,283 $12,004

Base Base

Base Base

Case-fatality odds ratio for patients with immunocompromising or other comorbid conditions Utility weights

Invasive pneumococcal disease Disabled Vaccine adverse event Costs Vaccine and administration Invasive pneumococcal disease

a

Using meningitis rates as a proxy for disability incidence.

[8]

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K.J. Smith et al. / Vaccine 27 (2009) 3159–3164

Table 4 Base case cost-effectiveness resultsa . Cohort age

Vaccination age

ICER

65

65, 65, 75 65, 75, 85 65, 70, 75, 80

$26,100 $88,400 $115,000 $215,000

75

75 75, 85

$71,300 $92,700

80

80 80, 85

$75,800 $548,000

ICER = incremental cost-effectiveness ratio. a Dominated strategies not included.

or epidemiologic data were varied over distributions based on data characteristics and ability to account for data skewness. 3. Results The incremental cost-effectiveness of PPV strategies are summarized in Table 4. In cohorts that begin the model at age 65, a single PPV at age 65 costs about $26,000 per QALY gained compared to no vaccination and, as such, would be considered a “good buy” by most economic criteria [24–27]. Two vaccinations, at ages 65 and 75, cost about $88,000 per QALY compared to a single vaccination, which is considered by one criterion to have moderate evidence for adoption [25], and by other criteria to be acceptable from an economic standpoint [24,26,27]. Vaccinating at ages 65, 75, and 85 cost $115,000 per QALY gained compared to two vaccinations; one criterion [25] would denote this as weak evidence for intervention adoption, while other criteria place it near the fringes of economic acceptability [24,26,27]. Four vaccinations (ages 65, 70, 75, and 80) cost >$200,000 per QALY compared to three vaccinations and thus were comparatively quite expensive. All other strategies were eliminated from consideration due to strict or extended dominance [28]. For cohorts beginning the model at age 75, vaccinating only at age 75 cost about $71,000 per QALY gained compared to no vaccination and vaccinating at ages 75 and 85 cost about $93,000 per QALY compared to one vaccination. Vaccinating at ages 75 and 80 was more expensive and less effective than vaccinating at 75 and 85, and thus was dominated. In 80-year-old cohorts, vaccinating once at age 80 remained economically reasonable (about $76,000 per QALY) compared to no vaccination, while vaccinating at 80 and 85 was extremely expensive. When analyses were performed using life years rather than quality adjusted life years, incremental costeffectiveness ratios decreased by 30–80% (data not shown). Vaccination strategy effects on IPD epidemiology in 65-year-old cohorts are summarized in Table 5. Without vaccination, the average lifetime risk of IPD in US 65-year olds is 0.65% and the risk of IPD death is 0.16%. A single vaccination decreases these risks by at least 12%, with risk further decreased by repeated vaccination. Similar relative risk reductions were observed with one and two dose PPV strategies in 75- and 80-year-old cohorts. Probabilistic sensitivity analysis results for the 65-year-old cohort are shown as a cost-effectiveness acceptability curve (Fig. 2), showing the likelihood that a given strategy would be considered cost-effective over a range of societal willingness-to-pay (or acceptability) thresholds. For 65 year olds, PPV at 65 only would be favored if the acceptability threshold ranged from $30,000 to $90,000 per QALY, vaccinations at 65 and 75 are favored if the threshold is $100,000–$160,000, and four vaccinations (65, 70, 75 and 80) are favored if the threshold is >$160,000. Probabilistic sensitivity analyses were also performed for the 75- and 80-year-old cohorts, which supported base case results. For each cohort, strategies that are

Table 5 Lifetime incidence of invasive pneumococcal disease (IPD) events from age 65 onward. Vaccination strategy

Incidence/100,000

Relative risk

Incremental relative risk reduction

IPD cases No vaccination 65 only 65, 70 65, 85 65, 80 65, 75 65, 71, 77 65, 70, 75 65, 75, 85 65, 70, 75, 80

651 557 533 528 523 515 498 495 487 468

– 0.86 0.82 0.81 0.80 0.79 0.76 0.76 0.75 0.72

– 14.4% 4.4% 0.8% 1.0% 1.5% 3.5% 0.5% 1.7% 3.8%

IPD deaths No vaccination 65 only 65, 70 65, 85 65, 80 65, 75 65, 71, 77 65, 70, 75 65, 75, 85 65, 70, 75, 80

155 137 131 128 127 127 123 123 118 115

– 0.88 0.85 0.83 0.82 0.82 0.79 0.79 0.76 0.74

– 11.8% 3.8% 2.7% 0.7% 0.1% 3.1% 0.3% 3.7% 2.8%

dominated in the base case analysis never become the most favored in the probabilistic sensitivity analysis. In a separate sensitivity analysis for each age cohort, we relaxed our base case assumptions of no prior vaccination and no loss of vaccine effectiveness (or tolerance) with repeat vaccination, examining the combined effects of prior PPV and a 20% decrease in PPV effectiveness due to tolerance. These results are summarized in Fig. 3. Of the strategies costing <$200,000 per QALY gained in the base case analysis, only the 65-, 75-, and 85-year-old strategy for 65-year-old cohorts rises to >$150,000 per QALY when prior vaccination and tolerance are assumed, and thus would be unacceptable if the societal willingness-to-pay threshold is $150,000. Under these same tolerance and prior vaccination assumptions, all multiple-dose PPV strategies cost >$100,000 per QALY in cohorts ages 65 or older, as do single-dose PPV strategies in 75- and 80-year olds, and thus become unacceptable if the willingness-to-pay threshold is $100,000 per QALY gained.

Fig. 2. The cost-effectiveness acceptability curve for 65-year-old cohorts, depicting the relative likelihood that pneumococcal polysaccharide vaccination strategies would be favored over a range of societal willingness-to-pay (or acceptability) thresholds.

K.J. Smith et al. / Vaccine 27 (2009) 3159–3164

Fig. 3. Sensitivity analysis results, when the combined effects of prior pneumococcal polysaccharide vaccination (PPV) and a 20% decrease in PPV effectiveness due to prior vaccination are assumed. Light bars depict base case results, dark bars show results when these assumptions are in place.

4. Discussion The CDC recommends a single PPV dose at age 65 unless a comorbid condition has been diagnosed and PPV given prior to age 65, when a second dose is recommended (either at age 65 or 5 years after the first PPV, whichever comes last). In this analysis, we examined the cost-effectiveness, in hypothetical patients aged 65 and older, of multiple-dose strategies and explored questions regarding the cost-effectiveness of PPV strategies for unvaccinated and previously vaccinated elderly patients. In base case analyses, we found that two and three dose strategies, with 10-year intervals between vaccinations, were economically reasonable in 65-year-old cohorts, as were one or two dose strategies in 75-year olds and singledose strategies in 80-year olds. However, when the combination of prior vaccination and diminished effectiveness of subsequent vaccination (i.e., tolerance) were considered, the cost-effectiveness of PPV in 75- and 80-year olds came into question, as it also did for multiple-dose strategies in 65-year olds. As in prior analyses [8,19], we found that the current recommended strategy of a single vaccination at age 65 for most adults decreases lifetime IPD risk. In our analysis, IPD risk decreased by about 14% when vaccination at 65 occurred, with more intensive strategies having small incremental effects. From the public health perspective, these findings suggest that further exploration of pneumococcal vaccination strategies is warranted in hopes of more substantial vaccination impact. A key consideration in multiple-dose PPV strategies is whether tolerance is induced by repeated vaccination and, if so, to what degree is vaccine effectiveness lost and how might this effect be mitigated by dosing interval [29–31]. For example, does a 5-year interval between PPVs induce more or less tolerance than a 10year interval? Whether tolerance occurs is controversial [30,31], with studies showing inconsistent evidence for its existence but trends that suggest it may occur with relatively short (1–6 years) revaccination intervals [7,30–32]. Concerns about side effects occurring with repeated PPVs previously discouraged consideration of multiple-dose PPV strategies. It has been convincingly shown that systemic side effects from repeated PPVs are infrequent and minor, although local reactions may occur [6,7]. Given these findings, regimen effectiveness and cost, not safety considerations, should drive PPV decision making in all age groups. PPV strategies using three or more vaccinations might also be considered unrealistic from clinical and policy perspectives, regardless of the presence or absence of side effects,

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given the logistic and adherence difficulties commonly seen in adult vaccination. In this analysis we show that strategies utilizing ≥3 vaccinations are also unlikely to be reasonable economically, unlike strategies using one or two vaccinations. Effective use of vaccines will become more important if antibiotic resistance becomes more widespread and frequent. If antibiotic resistance increases, our analysis may underestimate the benefit and overestimate the cost of PPV strategies, since we implicitly assume stable antibiotic resistance over time. Similarly, if antibiotic resistance decreases, our analysis would underestimate costs. Our analysis has several limitations. Since the effectiveness of PPV in pneumococcal disease prevention is unclear [33], we used an expert panel to estimate age-, duration-, and comorbidity-specific vaccine effectiveness. For IPD rates, we used CDC ABCs data rates, thus the validity of model results depends on how closely these rates correspond to true population rates; our results may not apply to populations at higher or lower risk. Finally, childhood vaccination with the 7-valent pneumococcal conjugate vaccine has caused significant declines in adult illness from pneumococcal serotypes contained in this vaccine [10,34], perhaps also decreasing PPV vaccine serotype coverage over time. We used ABCs data to model decreased serotype coverage as each cohort ages; future work using dynamic transmission modeling could provide more reliable estimates and account for future vaccine developments, including future use of the investigational 13-valent pneumococcal conjugate vaccine. In addition, pneumococcal conjugate vaccination (PCV) of adults may hold some promise in heightening protection against both IPD and noninvasive pneumonia [35], and not including this possibility in our analysis is a limitation of this study. Including adult PCV strategies in this type of analysis awaits further elucidation of its protective efficacy in adults and its interactions with PPV-related protection. We conclude that, for patients aged 65–80 years who have not previously received PPV, a single-dose PPV strategy at the time of presentation is both clinically indicated and economically reasonable. Multiple-dose regimens and revaccination after prior vaccination in these age groups may also be acceptable, depending on the possibility of vaccine tolerance and the cost-effectiveness willingness-to-pay threshold used. References [1] Prevention of pneumococcal disease: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 1997;46(RR-8):1–24. [2] Gardner P. A need to update and revise the pneumococcal vaccine recommendations for adults. Ann Intern Med 2003;138(12):999–1000. [3] Greene CM, Kyaw MH, Ray SM, Schaffner W, Lynfield R, Barrett NL, et al. Preventability of invasive pneumococcal disease and assessment of current polysaccharide vaccine recommendations for adults: United States, 2001–2003. Clin Infect Dis 2006;43(2):141–50. [4] Mufson MA, Krause HE, Schiffman G, Hughey DF. Pneumococcal antibody levels one decade after immunization of healthy adults. Am J Med Sci 1987;293(5):279–84. [5] Rodriguez-Barradas MC, Musher DM, Lahart C, Lacke C, Groover J, Watson D, et al. Antibody to capsular polysaccharides of Streptococcus pneumoniae after vaccination of human immunodeficiency virus-infected subjects with 23-valent pneumococcal vaccine. J Infect Dis 1992;165(3):553–6. [6] Walker FJ, Singleton RJ, Bulkow LR, Strikas RA, Butler JC. Reactions after 3 or more doses of pneumococcal polysaccharide vaccine in adults in Alaska. Clin Infect Dis 2005;40(12):1730–5. [7] Jackson LA, Benson P, Sneller VP, Butler JC, Thompson RS, Chen RT, et al. Safety of revaccination with pneumococcal polysaccharide vaccine. JAMA 1999;281(3):243–8. [8] Sisk JE, Whang W, Butler JC, Sneller VP, Whitney CG. Cost-effectiveness of vaccination against invasive pneumococcal disease among people 50 through 64 years of age: role of comorbid conditions and race. Ann Intern Med 2003;138(12):960–8. [9] Smith KJ, Zimmerman RK, Lin CJ, Nowalk MP, Ko FS, McEllistrem MC, et al. Alternative strategies for adult pneumococcal polysaccharide vaccination: a cost-effectiveness analysis. Vaccine 2008;26(11):1420–31. [10] Lexau CA, Lynfield R, Danila R, Pilishvili T, Facklam R, Farley MM, et al. Changing epidemiology of invasive pneumococcal disease among older adults in

3164

[11] [12]

[13]

[14] [15]

[16]

[17]

[18] [19]

[20] [21] [22] [23] [24]

K.J. Smith et al. / Vaccine 27 (2009) 3159–3164 the era of pediatric pneumococcal conjugate vaccine. JAMA 2005;294(16): 2043–51. Gold MR, Siegel JE, Russell LB, Weinstein MC, editors. Cost-effectiveness in health and medicine. New York: Oxford University Press; 1996. Moberley S, Holden J, Tatham DP, Andrews RM. Vaccines for preventing pneumococcal infection in adults. Cochrane Database Syst Rev 2008; (1). Art. No.: CD000422. doi:10.1002/14651858.CD000422.pub2. Vila-Corcoles A, Salsench E, Rodriguez-Blanco T, Ochoa-Gondar O, de Diego C, Valdivieso A, et al. Clinical effectiveness of 23-valent pneumococcal polysaccharide vaccine against pneumonia in middle-aged and older adults: a matched case-control study. Vaccine 2009;27(10):1504–10. Kannel WB, D’Agostino RB, Silbershatz H, Belanger AJ, Wilson PW, Levy D. Profile for estimating risk of heart failure. Arch Intern Med 1999;159(11):1197–204. Kannel WB, Vokonas PS. Demographics of the prevalence, incidence, and management of coronary heart disease in the elderly and in women. Ann Epidemiol 1992;2(1–2):5–14. Ho KK, Anderson KM, Kannel WB, Grossman W, Levy D. Survival after the onset of congestive heart failure in Framingham heart study subjects. Circulation 1993;88(1):107–15. Goldberg RJ, Larson M, Levy D. Factors associated with survival to 75 years of age in middle-aged men and women. The Framingham study. Arch Intern Med 1996;156(5):505–9. SEER age-specific cancer incidence, all sites. http://seer.cancer.gov/faststats/ sites.php. Fry 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(3–4):303–11. Medicare physician fee schedule look-up (CPT 90782). http://www.cms. hhs.gov/apps/pfslookup/. Pneumococcal vaccine (CPT 90732). http://www.cms.hhs.gov/MLNMatters Articles/downloads/MM4109.pdf. CDC vaccine price list. http://www.cdc.gov/nip/vfc/cdc vac price list.htm. Healthcare cost & utilization project (HCUP). http://www.ahrq.gov/data/hcup/. Murray CJ, Evans DB, Acharya A, Baltussen RM. Development of WHO guidelines on generalized cost-effectiveness analysis. Health Econ 2000;9(3):235–51.

[25] Laupacis A, Feeny D, Detsky AS, Tugwell PX. How attractive does a new technology have to be to warrant adoption and utilization? Tentative guidelines for using clinical and economic evaluations. Can Med Assoc J 1992;146(4):473– 81. [26] Braithwaite RS, Meltzer DO, King Jr JT, Leslie D, Roberts MS. What does the value of modern medicine say about the $50,000 per quality-adjusted life-year decision rule? Med Care 2008;46(4):349–56. [27] Ubel PA, Hirth RA, Chernew ME, Fendrick AM. What is the price of life and why doesn’t it increase at the rate of inflation? Arch Intern Med 2003;163(14):1637–41. [28] Cantor SB. Cost-effectiveness analysis, extended dominance, and ethics: a quantitative assessment. Med Decis Making 1994;14(3):259–65. [29] Artz AS, Ershler WB, Longo DL. Pneumococcal vaccination and revaccination of older adults. Clin Microbiol Rev 2003;16(2):308–18. [30] Fedson D, Musher D. Pneumococcal polysaccharide vaccine. In: Plotkin SA, Orenstein WA, editors. Vaccines. 4th ed. Philadelphia, PA: Saunders; 2004. [31] O’Brien KL, Hochman M, Goldblatt D. Combined schedules of pneumococcal conjugate and polysaccharide vaccines: is hyporesponsiveness an issue? Lancet Infect Dis 2007;7(9):597–606. [32] Davidson M, Bulkow LR, Grabman J, Parkinson AJ, Chamblee C, Williams WW, et al. Immunogenicity of pneumococcal revaccination in patients with chronic disease. Arch Intern Med 1994;154(19):2209–14. [33] Melegaro A, Edmunds WJ. The 23-valent pneumococcal polysaccharide vaccine. Part I. Efficacy of PPV in the elderly: a comparison of meta-analyses. Eur J Epidemiol 2004;19(4):353–63. [34] McBean AM, Jung K, Hebert PL. Decreasing invasive pneumococcal disease in the elderly: a state-level analysis. Vaccine 2006;24(27–28):5609–14. [35] Jackson LA, Neuzil KM, Nahm MH, Whitney CG, Yu O, Nelson JC, et al. Immunogenicity of varying dosages of 7-valent pneumococcal polysaccharide–protein conjugate vaccine in seniors previously vaccinated with 23-valent pneumococcal polysaccharide vaccine. Vaccine 2007;25(20):4029–37. [36] Gold MR, Franks P, McCoy KI, Fryback DG. Toward consistency in cost-utility analyses: using national measures to create condition-specific values. Med Care 1998;36(6):778–92.