- Email: [email protected]
Cost Effectiveness of Pertussis Vaccination in Adults
Cost Effectiveness of Pertussis Vaccination in Adults Grace M. Lee, MD, MPH, Trudy V. Murphy, MD, Susan Lett, MD, MPH, Margaret M. Cortese, MD, Katrina Kretsinger, MD, MA, Stephanie Schauer, PhD, Tracy A. Lieu, MD, MPH Background: Prior economic analyses have reached disparate conclusions about whether vaccinating adults against pertussis would be cost effective. Newly available data on pertussis incidence were used to evaluate the cost effectiveness of one-time adult vaccination and adult vaccination with decennial boosters. Methods:
A Markov model was used to calculate the health benefits, risks, costs, and cost effectiveness of the following strategies: (1) no adult pertussis vaccination, (2) one-time adult vaccination at 20 – 64 years, and (3) adult vaccination with decennial boosters. The impact of the severity of pertussis illness, vaccine adverse events, and herd immunity on model outcomes were also examined.
Results:
At a disease incidence of 360 per 100,000, the one-time adult vaccination strategy would prevent 2.8 million cases, and the decennial vaccination strategy would prevent 8.3 million cases. As disease incidence varied from 10 to 500 per 100,000, the one-time adult vaccination strategy was projected to prevent 79,000 to 3.8 million adult pertussis cases, while the decennial vaccination program would prevent 239,000 to 11.4 million cases. A one-time adult vaccination strategy would result in 106 million people vaccinated, or approximately 64% of the adult cohort, for a total program cost of $2.1 billion, while a decennial vaccination strategy would cost $6.7 billion. The one-time and decennial booster vaccination strategies result in cost-effectiveness ratios of ⬍$50,000 per quality-adjusted life year saved if disease incidence in adults were greater than 120 cases per 100,000 population.
Conclusions: Routine vaccination of adults aged 20 to 64 years with combined tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis is cost effective if pertussis incidence in this age group is greater than 120 per 100,000 population. (Am J Prev Med 2007;32(3):186 –193) © 2007 American Journal of Preventive Medicine
Introduction
T
he incidence of reported pertussis in the United States has been steadily increasing over the past 2 decades.1–5 The morbidity associated with pertussis in adolescents and adults can be severe and its economic impact substantial with considerable time missed from school and work for these individuals.2,6 –9 Combined tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccines specifically formulated for adolescents and adults up through age 64 years are now available for use in the United States. From the Department of Ambulatory Care and Prevention, Harvard Medical School and Harvard Pilgrim Health Care (Lee, Lieu), Divisions of General Pediatrics (Lieu) and Infectious Diseases (Lee), Children’s Hospital Boston, Massachusetts Department of Public Health (Lett, Schauer), Boston, Massachusetts; and the National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention (Murphy, Cortese, Kretsinger), and U.S. Public Health Service Commissioned Corps (Cortese, Kretsinger), Atlanta, Georgia Address correspondence and reprint requests to: Grace M. Lee, MD, MPH, Department of Ambulatory Care & Prevention, 133 Brookline Ave, 6th floor, Boston MA 02215. E-mail: grace_lee@ hphc.org.
186
Routine use of Tdap was recommended for all adolescents aged 11–12 years in June 2005, based on the disease and economic burden of pertussis in this age group, replacing the first dose of tetanus toxoid and reduced diphtheria toxoid vaccine (Td) as recommended by the Advisory Committee on Immunization Practices. Prior economic evaluations of adult pertussis vaccination strategies have reported disparate results. Purdy et al.10 found that a one-time adult vaccination strategy was cost saving, indicating that savings from disease prevention were greater than program costs. In contrast, Lee et al.11 found that an adult vaccination strategy with decennial boosters was not cost effective or cost saving. Several potential explanations may explain these differences. First, these studies examined different strategies for adult vaccination—a one-time adult vaccination strategy versus an adult strategy with decennial boosters. Second, baseline estimates for disease incidence varied significantly in these two studies. Purdy et al.10 used estimates of disease incidence in adults of 159 to 548 per 100,000 depending on the age group. Lee et al.11 used more conservative estimates
Am J Prev Med 2007;32(3) © 2007 American Journal of Preventive Medicine • Published by Elsevier Inc.
0749-3797/07/$–see front matter doi:10.1016/j.amepre.2006.10.016
from MA enhanced surveillance data of 11 per 100,000 in adults. Third, neither study made adjustments for a wider spectrum of disease severity with increased incidence. Adult strategies may have appeared to be cost effective or cost saving at high incidence rates because the studies assumed the distribution of the severity of disease was the same regardless of incidence. Finally, Purdy et al.10 used a time horizon of 10 years, whereas Lee et al.11 examined cost effectiveness over the lifetime of the cohort. Since these studies were conducted, additional information has become available on disease incidence in adults. A recently published large population-based study examined the efficacy of an acellular pertussis vaccine in adolescents and adults to prevent pertussis cough illness.12 In addition, Cortese et al.13 recently provided a reanalysis of the incidence rate for pertussis among adults studied in a Minnesota HMO. In anticipation of the Advisory Committee on Immunization Practice’s meeting in October 2005, analyses were conducted using these new data to assist policymakers with their decision about whether or not to recommend use of the Tdap product licensed for adults to replace Td as the booster in the U.S. The objective of this study was to estimate the cost effectiveness of vaccinating adults aged 20 – 64 years with a single dose of Tdap or with decennial Tdap boosters, instead of Td vaccination, and to explore the impact of incidence and severity of disease on cost effectiveness.
Methods Model A previously constructed Markov model was modified to calculate the health benefits, risks, costs, and cost effectiveness of alternative vaccination strategies for healthy adults using an analytic horizon of a lifetime.11 Appendix A (online at www.ajpm-online.net) shows a simplified version of the decision tree used for this analysis. The model allowed for waning immunity because of vaccination or disease over time, repeat vaccination for the decennial booster strategy, recurrent cases of pertussis, and age-specific death rates because of other causes. The model assumed there were no adult deaths because of pertussis disease or vaccination. In this analysis, the following strategies were evaluated: (1) no adult pertussis vaccination, (2) one-time adult pertussis vaccination at 20 – 64 years, where Tdap is administered instead of Td, and (3) adult pertussis vaccination with decennial boosters. In this computer simulation model, health outcomes and costs were calculated for a hypothetic cohort of 166 million adults in the U.S. aged 20 to 64 years over their lifetime. The age distribution of the initial cohort was the based on the 2000 U.S. Census as follows: 20 –29 years (23%), 30 –39 years (26%), 40 – 49 years (26%), 50 –59 years (19%), and 60 – 64 years (7%).14 The base case analysis assumed that childhood and adolescent pertussis vaccination programs were already established, and that the adult vaccination strategies had reached steady state in their implementation.
March 2007
Probabilities, costs, and utilities used in the model are described in Tables 1, 2, and 3. Medical costs included laboratory tests, ambulatory visits, hospitalizations, use of chest radiography, and antibiotics.8 Nonmedical costs included time missed from work, transportation, childcare and over-the-counter medications.8 Utilities refer to preferences for different health outcomes that are associated with disease or vaccine adverse events.25 Utilities based on the time trade-off method were obtained from the only published study on preferences in adults with pertussis illness.48 The mean durations of vaccination health states were assumed to be 2 days for anaphylaxis and 7 days for local or systemic reactions. Estimates for the mean durations of infant disease (80 days) and adult disease (87 days) were derived from available data.2,8,49, 50 Vaccine-mediated immunity was assumed to wane over a period of 10 to 15 years based on input from a expert panel.12,19 –24,48 The model’s structure and assumptions were similar to that in a previous study, but several important modifications were made.48 First, the incidence of reported adult pertussis was presented as a range from 10 to 500 per 100,000. Second, an additional pertussis health state was added to reflect the wide range of severity of illness in adults with pertussis (mild cough illness, moderate cough illness, severe cough illness, and pneumonia). This severity adjustment was performed to address concerns that many mild cases of pertussis may not come to the attention of the healthcare system, and that the most severe cases of pertussis were being identified by passive surveillance when the reported incidence was estimated to be 10 per 100,000. Thus, at a reported disease incidence of 10 per 100,000, the rates of mild cough, moderate cough, severe cough, and pneumonia were assumed to be 0%, 30%, 67%, and 3%, respectively.8 As reported disease incidence increased up to 500 per 100,000, the estimates for mild cough, moderate cough, severe cough, and pneumonia were assumed to be 38%, 21%, 40%, and 1%, respectively.15 Of note, complications from pertussis such as rib fractures and urinary incontinence are incorporated in estimates for medical and nonmedical costs and utilities in this model.8 Third, the incremental vaccine cost of Tdap over Td was estimated at $20 based on actual private and public sector prices.51 Finally, vaccine delivery rates in adults were estimated to be 57%– 66% based on reported estimates of decennial Td vaccination.33 Sensitivity analyses were performed to examine the impact of vaccine cost, vaccine efficacy, vaccine adverse events, discount rate, and herd immunity on model outcomes. The incremental vaccine cost of Tdap (versus Td) was varied from $5 to $35, and initial vaccine efficacy was varied from 50% to 100%. For incremental vaccine adverse events because of Tdap relative to Td, increases of 2% for local reactions, 1% for systemic reactions, and 0.0001% for anaphylaxis were assumed in the baseline analysis (Table 1).25–32 In an alternative analysis, it was assumed there were no incremental adverse events of Tdap compared to Td; thus, there was no disutility associated with Tdap vaccination because incremental adverse events were assumed not to occur. The discount rate was varied from 0%–5% in sensitivity analyses. The model structure was also evaluated to examine the assumption that death did not occur after pertussis illness in adults. In the U.S., only one pertussis death in an adult aged 20 – 64 years has been reported over a 15-year period from 1990 to 2004
Am J Prev Med 2007;32(3)
187
Table 1. Disease and vaccine probabilities used in the model
Variable
Base-case estimate or range
Alternative assumptions
Disease probabilities Disease incidence per 100,000 in adults
10 to 500
—
12,15–17
58.5
—
11,18
0 %¡ 38% 30% ¡ 21% 67% ¡ 40% 3% ¡ 1%
0% 30% 67% 3%
8,15
38.8% 58.5% 2% 0.7%
— — — —
11,18
87% 80% 78% 77% 76% 65% 55% 44% 34% 23% 19% 14% 10% 4% 0%
50%–100%
11,12,19–24
Disease incidence per 100,000 in infants Among adult patients with symptomatic pertussis Mild cough illness Moderate cough illness Severe cough illness Pneumonia Among infants with pertussis Respiratory illness (outpatient) Respiratory illness (hospitalized) Neurologic illness Death Vaccine probabilities Vaccine efficacy Year 1 Year 2 Year 3 Year 4 Year 5 Year 6 Year 7 Year 8 Year 9 Year 10 Year 11 Year 12 Year 13 Year 14 Year 15 Vaccine outcomes (incremental) Local reaction (Tdap vs Td) Systemic reaction (Tdap vs Td) Anaphylaxis Vaccine delivery in adults 20–49 years 50–64 years Herd immunity Discount rate (r) a
2% 1% 0.0001% 66% 57% 0%
0% 0% 0% — 0%–15% (one-time) 0%–45% (decennial) 0%–5%
3%
Source , MDPH,a unpublished data
11,25–31 11,25–31 32 33 34–37 25
Massachusetts Department of Public Health (MDPH).
when 22,947 adult cases were reported for a rate of 0.004% (CDC, unpublished data). The model was restructured to include death as a consequence of adult pertussis to assess the impact of a 0.004% death rate in adults in further sensitivity analyses. For herd immunity assumptions, data were derived from a published model of the transmission dynamics of pertussis and from published studies of the sources of infection of young infants.34 –37 Estimates from the literature were used, as the model did not incorporate transmission dynamics, which is needed to estimate disease reduction from herd immunity. Children and adolescents were assumed to have already been receiving pertussis vaccination via established programs, so that herd immunity primarily affected unvaccinated adults and infants. One-time adult vaccination was assumed to result in lower levels of herd immunity over the lifetime of a cohort than adult vaccination with decennial boosters because of
188
waning immunity after vaccination. Disease reduction from herd immunity was assumed to depend on vaccination rates in the adult population (57%– 66%) and time since last vaccination of the cohort. To assess the impact of herd immunity on the infant population, a separate decision analytic model was created for infants to determine costs and outcomes in this cohort (Appendix B, online at www.ajpmonline.net). Total costs, health outcomes, and cost-effectiveness ratios for infants and adults were calculated using an Excel spreadsheet. The baseline analysis conservatively assumed no herd immunity. Outcomes included cases of pertussis prevented, costs, and incremental cost-effectiveness ratios expressed as dollars per case prevented and dollars per quality-adjusted life year (QALY) saved. All costs were converted to 2005 U.S. dollars using the gross domestic product deflator.41 The healthcare and societal perspective was adopted, and future costs and
American Journal of Preventive Medicine, Volume 32, Number 3
www.ajpm-online.net
Table 2. Disease and vaccine costs used in the model in 2005 $US Base case estimate ($)
Variable Disease costs Medical costs for adults Mild cough illness Moderate cough illness Severe cough illness Pneumonia Medical cost for infants Respiratory illness (outpatient) Respiratory illness (hospitalization) Neurologic illness Death Nonmedical costs for adults Nonmedical costs for infants Respiratory disease (outpatient) Respiratory disease (hospitalization) Neurologic disease Death Vaccine costs Vaccine price (incremental Tdap vs Td) Vaccine administration Vaccine adverse events Local reactionb Systemic reactionb Anaphylaxis a
50 246 342 377
Source
8,38
, MDPHa unpublished data
99 6,577 6,315 14,197 466
39,40
42 437 669 660
41,42
20 0
43–46
1 1 2091
8
, MDPH,a unpublished data
47
Assumed Assumed 39
Massachusetts Department of Public Health (MDPH). Two percent of vaccine adverse events were assumed to be medically attended events requiring a healthcare provider visit.
b
health benefits were discounted at an annual rate of 3%.25 Because policymakers may wish to understand the total number of undiscounted cases prevented by a vaccination program, both discounted and undiscounted cases prevented are presented. All incremental cost-effectiveness ratios reported use both discounted costs and benefits in the ratio for consistency. A range of $50,000 –$100,000 per QALY was used as a benchmark for considering vaccination to be cost effective. Although no standard exists for what is considered cost effective, other well-established societal interventions colorectal cancer screening and dialysis for end-stage renal disease have cost-effectiveness ratios within or below this range.52–55 The base case analysis considered an analytic time horizon over the lifetime of the cohort25; however, the results were
Table 3. Utilities for disease and vaccination for pertussis Health state Adult disease utilities Mild cough illness Moderate cough illness Severe cough illness Pneumonia Adult vaccine utilities Local reaction Systemic reaction Anaphylaxis Infant disease utilities Respiratory illness Hospitalization Outpatient Neurologic illness
March 2007
Base-case estimate 0.90 0.85 0.81 0.82
Source Assumed 48 48 48
0.95 0.93 0.60
48
0.58 0.85 0.51
48
48 48
Assumed 48
also re-evaluated using a 10-year time frame for further comparison. Modeling was conducted in 2005 using TreeAge Pro 2005 Suite and Microsoft Excel 2000.56
Results Health Benefits and Risks Health outcomes were projected over the lifetime of a hypothetic cohort of 166 million adults aged 20 to 64 years. If disease incidence was 10 per 100,000, similar to national incidence rates from passive surveillance, approximately 760,000 cases would occur if no vaccination program were implemented. At a disease incidence of 360 per 100,000, similar to that observed by Strebel and colleagues,13,15 approximately 27 million adult cases would occur over the lifetime of the cohort. At incidence rates of 10, 360, or 500 per 100,000, the one-time adult vaccination strategy would potentially prevent 79,000 cases, 2.8 million cases, or 3.8 million cases, respectively (Table 4). The adult vaccination strategy with decennial boosters would potentially prevent 239,000 cases, 8.3 million cases, or 11.4 million cases at incidence rates of 10, 360, or 500 per 100,000, respectively. The frequency and severity of risks and benefits associated with adult vaccination programs were calculated as the total number of QALYs saved. At low disease incidence, the risks of vaccine adverse events outweighed the benefits of disease prevention. However, if disease incidence was more than 50 per 100,000, the benefits of preventing pertussis outAm J Prev Med 2007;32(3)
189
Table 4. Costs (2005 $US) and benefits of pertussis vaccination over the lifetime of a hypothetical cohort of 166 million adults aged 20 to 64 No vaccination program Incidence (cases per Pertussis 100,000) cases 10 50 100 150 200 250 300 350 400 450 500 a
763,000 3,804,000 7,583,000 11,335,000 15,063,000 18,766,000 22,444,000 26,097,000 29,726,000 33,331,000 36,913,000
One-time adult vaccination program
Decennial adult vaccination program
Cost of Discounted Net Discounted Net pertussis cases, Cases cases costs, in QALYs Cases cases costs, in QALYs in millions prevented preventeda millions saved prevented preventeda millions saved $301 $1462 $2830 $4092 $5241 $6268 $7166 $7933 $8564 $9058 $9415
79,000 392,000 781,000 1,167,000 1,550,000 1,930,000 2,307,000 2,681,000 3,052,000 3,421,000 3,786,000
70,000 349,000 696,000 1,041,000 1,383,000 1,722,000 2,060,000 2,394,000 2,727,000 3,057,000 3,385,000
$2003 $1800 $1562 $1342 $1142 $963 $807 $674 $565 $479 $418
(600) 239,000 147,000 10,600 1,188,000 730,000 24,100 2,365,000 1,454,000 37,100 3,530,000 2,173,000 49,600 4,684,000 2,885,000 61,300 5,827,000 3,591,000 72600 6,959,000 4,292,000 83,200 8,080,000 4,987,000 93,100 9,190,000 5,677,000 102,500 10,290,000 6,361,000 111,200 11,379,000 7,039,000
$4535 $4093 $3574 $3096 $2663 $2276 $1939 $1652 $1417 $1235 $1104
(1,700) 22,800 52,300 80,500 107,400 133,000 157,300 180,200 201,600 221,800 240,500
Total number of cases over the lifetime of the cohort discounted at a future rate of 3%.
weighed the risks of vaccination for both adult vaccination strategies (Table 4).
Costs and Cost Effectiveness The societal cost of adult pertussis without a vaccination program over the lifetime of the cohort ranged from $301 million to $9.4 billion, depending on assumptions about disease incidence. A one-time vaccination strategy for adults aged 20 to 64 years would result in 106 million people vaccinated, or approximately 64% of the adult cohort, for a vaccination program cost of $2.1 billion in this cohort. A decennial booster vaccination strategy would result in 335 million immunizations in the adult population for a total program cost of ⬃$6 billion for this cohort. Adult vaccination strategies could prevent considerable medical and nonmedical costs at high incidence rates of pertussis. The net cost of a one-time adult vaccination strategy was $2 billion at low disease incidence and $418 million at
high disease incidence (Table 4). The net cost of a decennial booster strategy ranged from $4.5 billion at low disease incidence to $1.1 billion at high disease incidence. Depending on the incidence assumptions, a one-time adult vaccination strategy ranged from $120 to $29,000 per pertussis case prevented and a decennial booster strategy ranged from $160 to $31,000 per pertussis case prevented (Table 5). At high disease incidence, for example, 500 per 100,000, the cost per QALY saved was $4000 to $5000 for the one-time adult vaccination and decennial booster strategies, respectively. At a low disease incidence of 10 per 100,000, the disutility of vaccine adverse events outweighed the benefit of disease prevention when QALYs were used as the metric of effectiveness. One-time and decennial booster vaccination strategies were less than $50,000 per QALY saved if disease incidence was greater than 120 cases per 100,000. The cost per case prevented and cost per
Table 5. Cost effectiveness of pertussis vaccination of a hypothetical cohort of 166 million adults from the societal perspective One-time adult vaccination program
Decennial adult vaccination program
Incidence (cases per 100,000)
$ per discounted pertussis case preventeda
$ per QALY saved
$ per discounted pertussis case prevented
$ per QALY saved
10 50 100 150 200 250 300 350 400 450 500
$29,000 $5,200 $2,200 $1,300 $830 $560 $390 $280 $210 $130 $120
Dominated $170,000 $65,000 $36,000 $23,000 $16,000 $11,000 $8,000 $6,000 $5,000 $4,000
$31,000 $5,600 $2,500 $1,400 $920 $630 $450 $330 $250 $190 $160
Dominated $179,000 $68,000 $38,000 $25,000 $17,000 $12,000 $9,000 $7,000 $6,000 $5,000
a
Cost and benefits are discounted at a future rate of 3%.
190
American Journal of Preventive Medicine, Volume 32, Number 3
www.ajpm-online.net
Figure 1. Two-way sensitivity analysis of pertussis incidence and incremental vaccine cost for the one-time adult vaccination strategy.
because of pertussis in adults was also examined, and no significant change in cost-effectiveness ratios was found (data not shown). Finally, the potential impact of herd immunity on the cost effectiveness of adult vaccination was considered. As the degree of herd immunity increased, the cost per QALY of adult vaccination strategies decreased. Herd immunity had a greater impact on cost effectiveness when disease incidence was low, suggesting that a certain threshold of cases prevented is needed for the intervention to appear cost effective (Appendix D, online at www.ajpm-online.net). When the time horizon of the analysis was changed to 10 years, there was no difference in cost-effectiveness ratios (data not shown).
Discussion QALY saved were slightly higher for the decennial adult vaccination strategy because of the incrementally higher cost of preventing each additional case of pertussis due to the persistence of low-level immunity after 10 years.
Sensitivity Analyses To understand the impact of severity of disease, vaccine cost, vaccine efficacy, and frequency of vaccine adverse events on the cost effectiveness of adult vaccination programs, alternative analyses were performed. The cost effectiveness ratios did not change appreciably if no adjustment was made for severity of illness, suggesting minimal impact of assuming a similar spectrum of disease severity at high incidence rates identified by active surveillance. An incremental vaccine cost of $5 resulted in a program that was cost effective at incidence rates less than 100 per 100,000 and cost saving at incidence rates higher than 100 per 100,000 (Figure 1). A higher incremental vaccine cost of $35, a lower vaccine efficacy of 50%, or a shorter duration of pertussis illness shifted the curve up so that a costeffectiveness ratio threshold of $50,000 was exceeded unless incidence rates were greater than 175 per 100,000 (Figures 1 and 2; Appendix C, online at www.ajpm-online.net). The results were not significantly affected by the assumption that there were no incremental vaccine adverse events. The only difference in these analyses was that at an incidence rate of 10 per 100,000, adult vaccination strategies had cost-effectiveness ratios of $700,000 to $800,000 per QALY saved instead of being dominated by no vaccination, because there was no disutility associated with vaccination. A dominated strategy is one that is more costly and results in fewer QALYs saved than another strategy. Varying the discount rate also did not significantly affect the cost effectiveness of an adult vaccination program (data not shown). The impact of restructuring the model to include death March 2007
Tdap vaccination for adults aged 20 – 64 years was found to be cost effective if pertussis incidence were at least 120 per 100,000. The range of plausible incidence estimates reported in the literature is broad, and costeffectiveness ratios ranged from $4000 per QALY saved to dominated (more costly and less effective than alternative strategies) as incidence was varied. At the very lowest assumption of disease incidence, the analysis suggested that the risks of vaccination outweighed the benefits. However, using more recent estimates from the literature of an incidence rate of 360 per 100,000, an adult vaccination program is cost effective.12,13 Accurate estimates of pertussis incidence have been difficult to determine because of the under-recognition of adult disease and limitations of currently available diagnostic tests. In addition, pertussis is an endemic disease that historically has epidemic cycles every 3– 4 years, so that incidence estimates must be interpreted within the context of the timing and geographic region. Given that disease incidence is an important driver of the cost effectiveness of an adult vaccination program, it is not surprising that conflicting estimates
Figure 2. Two-way sensitivity analysis of pertussis incidence and vaccine efficacy for the one-time adult vaccination strategy.
Am J Prev Med 2007;32(3)
191
have been reported. A recent review by Cortese et al.13 provides a comprehensive assessment of estimates of adult disease that range from 35 to 368 per 100,000 based on four prospective studies conducted in the U.S. The latest study, which was conducted within the context of a clinical trial with rigorous identification and follow-up of pertussis cases, demonstrated a combined adolescent and adult incidence rate of 368 per 100,000.12 Another study by Strebel et al.13,15 demonstrated a pertussis incidence rate of 361 per 100,000 for adults. Adjustments were made for disease severity by incidence rate in the analysis to evaluate whether the cost effectiveness of a vaccination program remained robust, even if the majority of cases were generally mild. A severity adjustment did not affect the cost effectiveness of an adult vaccination program, which is particularly helpful because decision makers may be concerned about bias in the interpretation of studies that reported high incidence rates. The cost effectiveness of a vaccination program was found to be critically dependent on vaccine cost and vaccine efficacy, which is not surprising. The disutility of vaccine adverse events was also considered in the baseline analysis. At high disease incidence, the benefits of vaccination far outweighed the risk of minor vaccine adverse events. When pertussis incidence was low, the cumulative impact of minor vaccine adverse events over a large population resulted in net worse health, as shown by lower estimates of QALYs saved. Some experts would recommend that minor vaccine adverse events be ignored in this cost effectiveness analysis. However, we believe their inclusion allows for a balanced assessment of the relative risks of both disease and vaccine outcomes. Including the effect of herd immunity in the model was found to modestly improve the cost effectiveness of the program at low disease incidence. Nonetheless, the additional benefit gained from herd immunity did not change the overall interpretation of this analysis, unless disease incidence was close to a threshold of 120 per 100,000. The degree of herd immunity that may result from an adult vaccination programs is unknown, but likely will depend on vaccine delivery rates and contact patterns among members of different age groups who have different risks of pertussis in the population. Further work to assess herd immunity because of adult pertussis vaccination is needed. In conclusion, a Tdap vaccination program in adults aged 20 – 64 years to prevent pertussis is likely to have benefits that outweigh vaccination risks, and is cost effective if the incidence of pertussis is greater than 120 per 100,000 population in this age group. We thank Charles LeBaron and Donna Rusinak for their invaluable contributions to this work. G.M.L. was supported by the Agency for Healthcare Research and Quality, U.S. Department of Health and Human
192
Services (K-08 HS013908-01 A1). Original analyses were funded by the National Immunization Program and Centers for Disease Control and Prevention via cooperative agreement with the Association of Teachers of Preventive Medicine, Task order #TS-0675. This work was presented to the Advisory Committee on Immunization Practices, October 2005, Atlanta GA. No financial conflict of interest was reported by the authors of this paper.
References 1. Farizo KM, Cochi SL, Zell ER, Brink EW, Wassilak SG, Patriarca PA. Epidemiological features of pertussis in the United States, 1980 –1989. Clin Infect Dis 1992;14:708 –19. 2. Yih WK, Lett SM, des Vignes FN, Garrison KM, Sipe PL, Marchant CD. The increasing incidence of pertussis in Massachusetts adolescents and adults, 1989 –1998. J Infect Dis 2000;182:1409 –16. 3. Pertussis—United States, 1997–2000. MMWR Morb Mortal Wkly Rep. 2002;51:73– 6. 4. Black S. Epidemiology of pertussis. Pediatr Infect Dis J 1997;16(4 Suppl):S85–9. 5. Guris D, Strebel PM, Bardenheier B, et al. Changing epidemiology of pertussis in the United States: increasing reported incidence among adolescents and adults, 1990 –1996. Clin Infect Dis 1999;28:1230 –7. 6. De Serres G, Shadmani R, Duval B, et al. Morbidity of pertussis in adolescents and adults. J Infect Dis 2000;182:174 –9. 7. Thomas PF, McIntyre PB, Jalaludin BB. Survey of pertussis morbidity in adults in western Sydney. Med J Aust 2000;173:74 – 6. 8. Lee GM, Lett S, Schauer S, et al. Societal costs and morbidity of pertussis in adolescents and adults. Clin Infect Dis 2004;39:1572– 80. 9. Postels-Multani S, Schmitt HJ, Wirsing von Konig CH, Bock HL, Bogaerts H. Symptoms and complications of pertussis in adults. Infection 1995;23:139 – 42. 10. Purdy KW, Hay JW, Botteman MF, Ward JI. Evaluation of strategies for use of acellular pertussis vaccine in adolescents and adults: a cost– benefit analysis. Clin Infect Dis 2004;39:20 – 8. 11. Lee GM, Lebaron C, Murphy TV, Lett S, Schauer S, Lieu TA. Pertussis in adolescents and adults: should we vaccinate? Pediatrics 2005;115:1675– 84. 12. Ward JI, Cherry JD, Chang SJ, et al. Efficacy of an acellular pertussis vaccine among adolescents and adults. N Engl J Med 2005;353:1555– 63. 13. Cortese MM, Baughman A, Brown K, Srivastava P. A “new age” for pertussis prevention in the United States: seizing opportunities through adult vaccination. Am J Prev Med 2007;32:177– 85. 14. http://www.census.gov/popest/states/NST-ann-est.html. 15. Strebel P, Nordin J, Edwards K, et al. Population-based incidence of pertussis among adolescents and adults, Minnesota, 1995–1996. J Infect Dis 2001;183:1353–9. 16. Nennig ME, Shinefield HR, Edwards KM, Black SB, Fireman BH. Prevalence and incidence of adult pertussis in an urban population. JAMA 1996;275:1672– 4. 17. Mink CM, Cherry JD, Christenson P, et al. A search for Bordetella pertussis infection in university students. Clin Infect Dis 1992;14:464 –71. 18. Centers for Disease Control and Prevention. Pertussis—United States, 1997–2000. JAMA 2002;287:977–9. 19. Ward J. The APERT Study. Paper presented at the National Consensus Conference on Pertussis, May 25–28, 2002, Toronto. 20. Ward JI, APERT Study Group. Pertussis epidemiology and acellular pertussis vaccine efficacy in older children: NIH APERT Multicenter Pertussis Trial. Paper presented at the Pediatric Academic Societies Annual Meeting, 2001, Baltimore MD. 21. Jenkinson D. Duration of effectiveness of pertussis vaccine: evidence from a 10 year community study. Br Med J (Clin Res Ed) 1988;296:612– 4. 22. Lambert HJ. Epidemiology of a small pertussis outbreak in Kent County, Michigan. Public Health Rep 1965;80:365–7. 23. Cattaneo LA, Reed GW, Haase DH, Wills MJ, Edwards KM. The seroepidemiology of Bordetella pertussis infections: a study of persons ages 1– 65 years. J Infect Dis 1996;173:1256 –9. 24. Ramsay ME, Farrington CP, Miller E. Age-specific efficacy of pertussis vaccine during epidemic and non-epidemic periods. Epidemiol Infect 1993;111:41– 8.
American Journal of Preventive Medicine, Volume 32, Number 3
www.ajpm-online.net
25. Gold MR, Siegel JE, Russell LB, Weinstein MC. Cost-effectiveness in health and medicine. New York: Oxford University Press; 1996. 26. Van der Wielen M, Van Damme P, Joossens E, Francois G, Meurice F, Ramalho A. A randomised controlled trial with a diphtheria–tetanus– acellular pertussis (dTap) vaccine in adults. Vaccine 2000;18:2075– 82. 27. Halperin SA, Smith B, Russell M, et al. An adult formulation of a five-component acellular pertussis vaccine combined with diphtheria and tetanus toxoids is safe and immunogenic in adolescents and adults. Vaccine 2000;18:1312–9. 28. Halperin SA, Smith B, Russell M, et al. Adult formulation of a five component acellular pertussis vaccine combined with diphtheria and tetanus toxoids and inactivated poliovirus vaccine is safe and immunogenic in adolescents and adults. Pediatr Infect Dis J 2000;19:276 – 83. 29. Rennels MB. Extensive swelling reactions occurring after booster doses of diphtheria–tetanus–acellular pertussis vaccines. Semin Pediatr Infect Dis 2003;14:196 – 8. 30. Rennels MB, Deloria MA, Pichichero ME, et al. Extensive swelling after booster doses of acellular pertussis–tetanus– diphtheria vaccines. Pediatrics 2000;105:e12. 31. Jackson LA, Carste BA, Malais D, Froeschle J. Retrospective populationbased assessment of medically attended injection site reactions, seizures, allergic responses and febrile episodes after acellular pertussis vaccine combined with diphtheria and tetanus toxoids. Pediatr Infect Dis J 2002;21:781– 6. 32. Bohlke K, Davis RL, Marcy SM, et al. Risk of anaphylaxis after vaccination of children and adolescents. Pediatrics 2003;112:815–20. 33. Singleton JA, Greby SM, Wooten KG, Walker FJ, Strikas R. Influenza, pneumococcal, and tetanus toxoid vaccination of adults—United States, 1993–7. MMWR CDC Surveill Summ 2000;49:39 – 62. 34. Van Rie A, Hethcote HW. Adolescent and adult pertussis vaccination: computer simulations of five new strategies. Vaccine 2004;22:3154 – 65. 35. Deen JL, Mink CA, Cherry JD, et al. Household contact study of Bordetella pertussis infections. Clin Infect Dis 1995;21:1211–9. 36. Crowcroft NS, Booy R, Harrison T, et al. Severe and unrecognised: pertussis in UK infants. Arch Dis Child 2003;88:802– 6. 37. Bisgard KM, Pascual FB, Ehresmann KR, et al. Infant pertussis: who was the source? Pediatr Infect Dis J 2004;23:985–9. 38. Bourgeois F, Goldmann DA, Ross-Degnan D, Hibberd P, Lee GM. Health service utilization and economic burden of daycare-associated illness. Abstract presented at the Pediatric Academic Societies’ Annual Meeting, San Francisco CA, 2006. 39. Centers for Medicare & Medicaid Services (CMS) HHS. Medicare Program: changes to the hospital inpatient prospective payment systems and rates and costs of graduate medical education: fiscal year 2002 rates; Provisions
March 2007
40.
41. 42. 43. 44. 45. 46. 47.
48.
49.
50. 51. 52.
53.
54.
55.
56.
of the Balanced Budget Refinement Act of 1999; and Provisions of the Medicare, Medicaid, and SCHIP Benefits Improvement and Protection Act of 2000: Department of Health and Human Services, Centers for Medicare & Medicaid Services, August 1, 2001. Vol. 66, No. 148, 42 CFR Parts 405, 410, 412. Morris M, Tang S. Pediatric Service Utilization, Fees and Managed Care Arrangements, 2001 report based on 1999 data. Elk Grove Village: American Academy of Pediatrics; 2001. NASA. Available at http://www.jsc.nasa.gov/bu2/inflateGDP.html (Accessed October 30, 2005). U.S. Census Bureau. Available at www.census.gov/hhes/income/ income00/inctab7.html. Arrow Pharmaceuticals. Available at http://www.arrowpharma.com/about. cfm. Aventis Pasteur—Canada, 1-416-667-2700. Bundaberg & District, Division of General Practice. Available at http://www.widebaydgp.org.au/News/newslett/Sept-Oct2002a.pdf. http://www.worldwidevaccines.com/by_country/gsk_vaccines.asp. Zhou W, Pool V, Iskander JK, et al. Surveillance for safety after immunization: vaccine adverse event reporting system (VAERS)—United States, 1991–2001. MMWR Surveill Summ 2003;52:1–24. Lee gm, Salomon JA, LeBaron CW, Lieu TA. Health-state valuations for pertussis: methods for valuing short-term health states. Health Qual Life Outcomes 2005;3:17. Tozzi AE, Rava L, Ciofi degli Atti ML, Salmaso S. Clinical presentation of pertussis in unvaccinated and vaccinated children in the first six years of life. Pediatrics 2003;112:1069 –75. Birkebaek NH, Kristiansen M, Seefeldt T, et al. Bordetella pertussis and chronic cough in adults. Clin Infect Dis 1999;29:1239 – 42. http://www.cdc.gov/nip/vfc/cdc_vac_price_list.htm#adult. Stone PW, Teutsch S, Chapman RH, Bell C, Goldie SJ, Neumann PJ. Cost-utility analyses of clinical preventive services: published ratios, 1976 – 1997. Am J Prev Med 2000;19:15–23. Chapman RH, Stone PW, Sandberg EA, Bell C, Neumann PJ. A comprehensive league table of cost-utility ratios and a sub-table of “panel-worthy” studies. Med Decis Making 2000;20:451– 67. Pignone M, Saha S, Hoerger T, Mandelblatt J. Cost-effectiveness analyses of colorectal cancer screening: a systematic review for the U.S. Preventive Services Task Force. Ann Intern Med 2002;137:96 –104. Winkelmayer WC, Weinstein MC, Mittleman MA, Glynn RJ, Pliskin JS. Health economic evaluations: the special case of end-stage renal disease treatment. Med Decis Making 2002;22:417–30. TreeAge Pro 2005 Suite [computer program]. Version 0.4. Williamstown MA: TreeAge Software, Inc.; 2005.
Am J Prev Med 2007;32(3)
193
Appendix A—Simplified decision tree structure for adult pertussis vaccination
Appendix B—Simplified decision tree structure for infant disease
193.e1
American Journal of Preventive Medicine, Volume 32, Number 3
Incremental cost per QALY
Appendix C—Two-way sensitivity analysis of pertussis incidence and duration of pertussis health states for the one-time adult vaccination strategy
44 days
87 days (baseline)
174 days
$200,000 $150,000 $100,000 $50,000 $0 0
100
200
300
400
500
Incidence per 100,000 Appendix D—Impact of herd immunity on the cost effectiveness of a decennial booster strategy
Incremental cost per QALY
Baseline 0%
Herd 15%
Herd 30%
Herd 45%
$200,000 $150,000 $100,000 $50,000 $0
100
200
300
400
500
Incidence (per 100,000)
Am J Prev Med 2007;32(3)
193.e2
A Markov model was used to calculate the health benefits, risks, costs, and cost effectiveness of the following strategies: (1) no adult pertussis vaccination, (2) one-time adult vaccination at 20 – 64 years, and (3) adult vaccination with decennial boosters. The impact of the severity of pertussis illness, vaccine adverse events, and herd immunity on model outcomes were also examined.
Results:
At a disease incidence of 360 per 100,000, the one-time adult vaccination strategy would prevent 2.8 million cases, and the decennial vaccination strategy would prevent 8.3 million cases. As disease incidence varied from 10 to 500 per 100,000, the one-time adult vaccination strategy was projected to prevent 79,000 to 3.8 million adult pertussis cases, while the decennial vaccination program would prevent 239,000 to 11.4 million cases. A one-time adult vaccination strategy would result in 106 million people vaccinated, or approximately 64% of the adult cohort, for a total program cost of $2.1 billion, while a decennial vaccination strategy would cost $6.7 billion. The one-time and decennial booster vaccination strategies result in cost-effectiveness ratios of ⬍$50,000 per quality-adjusted life year saved if disease incidence in adults were greater than 120 cases per 100,000 population.
Conclusions: Routine vaccination of adults aged 20 to 64 years with combined tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis is cost effective if pertussis incidence in this age group is greater than 120 per 100,000 population. (Am J Prev Med 2007;32(3):186 –193) © 2007 American Journal of Preventive Medicine
Introduction
T
he incidence of reported pertussis in the United States has been steadily increasing over the past 2 decades.1–5 The morbidity associated with pertussis in adolescents and adults can be severe and its economic impact substantial with considerable time missed from school and work for these individuals.2,6 –9 Combined tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccines specifically formulated for adolescents and adults up through age 64 years are now available for use in the United States. From the Department of Ambulatory Care and Prevention, Harvard Medical School and Harvard Pilgrim Health Care (Lee, Lieu), Divisions of General Pediatrics (Lieu) and Infectious Diseases (Lee), Children’s Hospital Boston, Massachusetts Department of Public Health (Lett, Schauer), Boston, Massachusetts; and the National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention (Murphy, Cortese, Kretsinger), and U.S. Public Health Service Commissioned Corps (Cortese, Kretsinger), Atlanta, Georgia Address correspondence and reprint requests to: Grace M. Lee, MD, MPH, Department of Ambulatory Care & Prevention, 133 Brookline Ave, 6th floor, Boston MA 02215. E-mail: grace_lee@ hphc.org.
186
Routine use of Tdap was recommended for all adolescents aged 11–12 years in June 2005, based on the disease and economic burden of pertussis in this age group, replacing the first dose of tetanus toxoid and reduced diphtheria toxoid vaccine (Td) as recommended by the Advisory Committee on Immunization Practices. Prior economic evaluations of adult pertussis vaccination strategies have reported disparate results. Purdy et al.10 found that a one-time adult vaccination strategy was cost saving, indicating that savings from disease prevention were greater than program costs. In contrast, Lee et al.11 found that an adult vaccination strategy with decennial boosters was not cost effective or cost saving. Several potential explanations may explain these differences. First, these studies examined different strategies for adult vaccination—a one-time adult vaccination strategy versus an adult strategy with decennial boosters. Second, baseline estimates for disease incidence varied significantly in these two studies. Purdy et al.10 used estimates of disease incidence in adults of 159 to 548 per 100,000 depending on the age group. Lee et al.11 used more conservative estimates
Am J Prev Med 2007;32(3) © 2007 American Journal of Preventive Medicine • Published by Elsevier Inc.
0749-3797/07/$–see front matter doi:10.1016/j.amepre.2006.10.016
from MA enhanced surveillance data of 11 per 100,000 in adults. Third, neither study made adjustments for a wider spectrum of disease severity with increased incidence. Adult strategies may have appeared to be cost effective or cost saving at high incidence rates because the studies assumed the distribution of the severity of disease was the same regardless of incidence. Finally, Purdy et al.10 used a time horizon of 10 years, whereas Lee et al.11 examined cost effectiveness over the lifetime of the cohort. Since these studies were conducted, additional information has become available on disease incidence in adults. A recently published large population-based study examined the efficacy of an acellular pertussis vaccine in adolescents and adults to prevent pertussis cough illness.12 In addition, Cortese et al.13 recently provided a reanalysis of the incidence rate for pertussis among adults studied in a Minnesota HMO. In anticipation of the Advisory Committee on Immunization Practice’s meeting in October 2005, analyses were conducted using these new data to assist policymakers with their decision about whether or not to recommend use of the Tdap product licensed for adults to replace Td as the booster in the U.S. The objective of this study was to estimate the cost effectiveness of vaccinating adults aged 20 – 64 years with a single dose of Tdap or with decennial Tdap boosters, instead of Td vaccination, and to explore the impact of incidence and severity of disease on cost effectiveness.
Methods Model A previously constructed Markov model was modified to calculate the health benefits, risks, costs, and cost effectiveness of alternative vaccination strategies for healthy adults using an analytic horizon of a lifetime.11 Appendix A (online at www.ajpm-online.net) shows a simplified version of the decision tree used for this analysis. The model allowed for waning immunity because of vaccination or disease over time, repeat vaccination for the decennial booster strategy, recurrent cases of pertussis, and age-specific death rates because of other causes. The model assumed there were no adult deaths because of pertussis disease or vaccination. In this analysis, the following strategies were evaluated: (1) no adult pertussis vaccination, (2) one-time adult pertussis vaccination at 20 – 64 years, where Tdap is administered instead of Td, and (3) adult pertussis vaccination with decennial boosters. In this computer simulation model, health outcomes and costs were calculated for a hypothetic cohort of 166 million adults in the U.S. aged 20 to 64 years over their lifetime. The age distribution of the initial cohort was the based on the 2000 U.S. Census as follows: 20 –29 years (23%), 30 –39 years (26%), 40 – 49 years (26%), 50 –59 years (19%), and 60 – 64 years (7%).14 The base case analysis assumed that childhood and adolescent pertussis vaccination programs were already established, and that the adult vaccination strategies had reached steady state in their implementation.
March 2007
Probabilities, costs, and utilities used in the model are described in Tables 1, 2, and 3. Medical costs included laboratory tests, ambulatory visits, hospitalizations, use of chest radiography, and antibiotics.8 Nonmedical costs included time missed from work, transportation, childcare and over-the-counter medications.8 Utilities refer to preferences for different health outcomes that are associated with disease or vaccine adverse events.25 Utilities based on the time trade-off method were obtained from the only published study on preferences in adults with pertussis illness.48 The mean durations of vaccination health states were assumed to be 2 days for anaphylaxis and 7 days for local or systemic reactions. Estimates for the mean durations of infant disease (80 days) and adult disease (87 days) were derived from available data.2,8,49, 50 Vaccine-mediated immunity was assumed to wane over a period of 10 to 15 years based on input from a expert panel.12,19 –24,48 The model’s structure and assumptions were similar to that in a previous study, but several important modifications were made.48 First, the incidence of reported adult pertussis was presented as a range from 10 to 500 per 100,000. Second, an additional pertussis health state was added to reflect the wide range of severity of illness in adults with pertussis (mild cough illness, moderate cough illness, severe cough illness, and pneumonia). This severity adjustment was performed to address concerns that many mild cases of pertussis may not come to the attention of the healthcare system, and that the most severe cases of pertussis were being identified by passive surveillance when the reported incidence was estimated to be 10 per 100,000. Thus, at a reported disease incidence of 10 per 100,000, the rates of mild cough, moderate cough, severe cough, and pneumonia were assumed to be 0%, 30%, 67%, and 3%, respectively.8 As reported disease incidence increased up to 500 per 100,000, the estimates for mild cough, moderate cough, severe cough, and pneumonia were assumed to be 38%, 21%, 40%, and 1%, respectively.15 Of note, complications from pertussis such as rib fractures and urinary incontinence are incorporated in estimates for medical and nonmedical costs and utilities in this model.8 Third, the incremental vaccine cost of Tdap over Td was estimated at $20 based on actual private and public sector prices.51 Finally, vaccine delivery rates in adults were estimated to be 57%– 66% based on reported estimates of decennial Td vaccination.33 Sensitivity analyses were performed to examine the impact of vaccine cost, vaccine efficacy, vaccine adverse events, discount rate, and herd immunity on model outcomes. The incremental vaccine cost of Tdap (versus Td) was varied from $5 to $35, and initial vaccine efficacy was varied from 50% to 100%. For incremental vaccine adverse events because of Tdap relative to Td, increases of 2% for local reactions, 1% for systemic reactions, and 0.0001% for anaphylaxis were assumed in the baseline analysis (Table 1).25–32 In an alternative analysis, it was assumed there were no incremental adverse events of Tdap compared to Td; thus, there was no disutility associated with Tdap vaccination because incremental adverse events were assumed not to occur. The discount rate was varied from 0%–5% in sensitivity analyses. The model structure was also evaluated to examine the assumption that death did not occur after pertussis illness in adults. In the U.S., only one pertussis death in an adult aged 20 – 64 years has been reported over a 15-year period from 1990 to 2004
Am J Prev Med 2007;32(3)
187
Table 1. Disease and vaccine probabilities used in the model
Variable
Base-case estimate or range
Alternative assumptions
Disease probabilities Disease incidence per 100,000 in adults
10 to 500
—
12,15–17
58.5
—
11,18
0 %¡ 38% 30% ¡ 21% 67% ¡ 40% 3% ¡ 1%
0% 30% 67% 3%
8,15
38.8% 58.5% 2% 0.7%
— — — —
11,18
87% 80% 78% 77% 76% 65% 55% 44% 34% 23% 19% 14% 10% 4% 0%
50%–100%
11,12,19–24
Disease incidence per 100,000 in infants Among adult patients with symptomatic pertussis Mild cough illness Moderate cough illness Severe cough illness Pneumonia Among infants with pertussis Respiratory illness (outpatient) Respiratory illness (hospitalized) Neurologic illness Death Vaccine probabilities Vaccine efficacy Year 1 Year 2 Year 3 Year 4 Year 5 Year 6 Year 7 Year 8 Year 9 Year 10 Year 11 Year 12 Year 13 Year 14 Year 15 Vaccine outcomes (incremental) Local reaction (Tdap vs Td) Systemic reaction (Tdap vs Td) Anaphylaxis Vaccine delivery in adults 20–49 years 50–64 years Herd immunity Discount rate (r) a
2% 1% 0.0001% 66% 57% 0%
0% 0% 0% — 0%–15% (one-time) 0%–45% (decennial) 0%–5%
3%
Source , MDPH,a unpublished data
11,25–31 11,25–31 32 33 34–37 25
Massachusetts Department of Public Health (MDPH).
when 22,947 adult cases were reported for a rate of 0.004% (CDC, unpublished data). The model was restructured to include death as a consequence of adult pertussis to assess the impact of a 0.004% death rate in adults in further sensitivity analyses. For herd immunity assumptions, data were derived from a published model of the transmission dynamics of pertussis and from published studies of the sources of infection of young infants.34 –37 Estimates from the literature were used, as the model did not incorporate transmission dynamics, which is needed to estimate disease reduction from herd immunity. Children and adolescents were assumed to have already been receiving pertussis vaccination via established programs, so that herd immunity primarily affected unvaccinated adults and infants. One-time adult vaccination was assumed to result in lower levels of herd immunity over the lifetime of a cohort than adult vaccination with decennial boosters because of
188
waning immunity after vaccination. Disease reduction from herd immunity was assumed to depend on vaccination rates in the adult population (57%– 66%) and time since last vaccination of the cohort. To assess the impact of herd immunity on the infant population, a separate decision analytic model was created for infants to determine costs and outcomes in this cohort (Appendix B, online at www.ajpmonline.net). Total costs, health outcomes, and cost-effectiveness ratios for infants and adults were calculated using an Excel spreadsheet. The baseline analysis conservatively assumed no herd immunity. Outcomes included cases of pertussis prevented, costs, and incremental cost-effectiveness ratios expressed as dollars per case prevented and dollars per quality-adjusted life year (QALY) saved. All costs were converted to 2005 U.S. dollars using the gross domestic product deflator.41 The healthcare and societal perspective was adopted, and future costs and
American Journal of Preventive Medicine, Volume 32, Number 3
www.ajpm-online.net
Table 2. Disease and vaccine costs used in the model in 2005 $US Base case estimate ($)
Variable Disease costs Medical costs for adults Mild cough illness Moderate cough illness Severe cough illness Pneumonia Medical cost for infants Respiratory illness (outpatient) Respiratory illness (hospitalization) Neurologic illness Death Nonmedical costs for adults Nonmedical costs for infants Respiratory disease (outpatient) Respiratory disease (hospitalization) Neurologic disease Death Vaccine costs Vaccine price (incremental Tdap vs Td) Vaccine administration Vaccine adverse events Local reactionb Systemic reactionb Anaphylaxis a
50 246 342 377
Source
8,38
, MDPHa unpublished data
99 6,577 6,315 14,197 466
39,40
42 437 669 660
41,42
20 0
43–46
1 1 2091
8
, MDPH,a unpublished data
47
Assumed Assumed 39
Massachusetts Department of Public Health (MDPH). Two percent of vaccine adverse events were assumed to be medically attended events requiring a healthcare provider visit.
b
health benefits were discounted at an annual rate of 3%.25 Because policymakers may wish to understand the total number of undiscounted cases prevented by a vaccination program, both discounted and undiscounted cases prevented are presented. All incremental cost-effectiveness ratios reported use both discounted costs and benefits in the ratio for consistency. A range of $50,000 –$100,000 per QALY was used as a benchmark for considering vaccination to be cost effective. Although no standard exists for what is considered cost effective, other well-established societal interventions colorectal cancer screening and dialysis for end-stage renal disease have cost-effectiveness ratios within or below this range.52–55 The base case analysis considered an analytic time horizon over the lifetime of the cohort25; however, the results were
Table 3. Utilities for disease and vaccination for pertussis Health state Adult disease utilities Mild cough illness Moderate cough illness Severe cough illness Pneumonia Adult vaccine utilities Local reaction Systemic reaction Anaphylaxis Infant disease utilities Respiratory illness Hospitalization Outpatient Neurologic illness
March 2007
Base-case estimate 0.90 0.85 0.81 0.82
Source Assumed 48 48 48
0.95 0.93 0.60
48
0.58 0.85 0.51
48
48 48
Assumed 48
also re-evaluated using a 10-year time frame for further comparison. Modeling was conducted in 2005 using TreeAge Pro 2005 Suite and Microsoft Excel 2000.56
Results Health Benefits and Risks Health outcomes were projected over the lifetime of a hypothetic cohort of 166 million adults aged 20 to 64 years. If disease incidence was 10 per 100,000, similar to national incidence rates from passive surveillance, approximately 760,000 cases would occur if no vaccination program were implemented. At a disease incidence of 360 per 100,000, similar to that observed by Strebel and colleagues,13,15 approximately 27 million adult cases would occur over the lifetime of the cohort. At incidence rates of 10, 360, or 500 per 100,000, the one-time adult vaccination strategy would potentially prevent 79,000 cases, 2.8 million cases, or 3.8 million cases, respectively (Table 4). The adult vaccination strategy with decennial boosters would potentially prevent 239,000 cases, 8.3 million cases, or 11.4 million cases at incidence rates of 10, 360, or 500 per 100,000, respectively. The frequency and severity of risks and benefits associated with adult vaccination programs were calculated as the total number of QALYs saved. At low disease incidence, the risks of vaccine adverse events outweighed the benefits of disease prevention. However, if disease incidence was more than 50 per 100,000, the benefits of preventing pertussis outAm J Prev Med 2007;32(3)
189
Table 4. Costs (2005 $US) and benefits of pertussis vaccination over the lifetime of a hypothetical cohort of 166 million adults aged 20 to 64 No vaccination program Incidence (cases per Pertussis 100,000) cases 10 50 100 150 200 250 300 350 400 450 500 a
763,000 3,804,000 7,583,000 11,335,000 15,063,000 18,766,000 22,444,000 26,097,000 29,726,000 33,331,000 36,913,000
One-time adult vaccination program
Decennial adult vaccination program
Cost of Discounted Net Discounted Net pertussis cases, Cases cases costs, in QALYs Cases cases costs, in QALYs in millions prevented preventeda millions saved prevented preventeda millions saved $301 $1462 $2830 $4092 $5241 $6268 $7166 $7933 $8564 $9058 $9415
79,000 392,000 781,000 1,167,000 1,550,000 1,930,000 2,307,000 2,681,000 3,052,000 3,421,000 3,786,000
70,000 349,000 696,000 1,041,000 1,383,000 1,722,000 2,060,000 2,394,000 2,727,000 3,057,000 3,385,000
$2003 $1800 $1562 $1342 $1142 $963 $807 $674 $565 $479 $418
(600) 239,000 147,000 10,600 1,188,000 730,000 24,100 2,365,000 1,454,000 37,100 3,530,000 2,173,000 49,600 4,684,000 2,885,000 61,300 5,827,000 3,591,000 72600 6,959,000 4,292,000 83,200 8,080,000 4,987,000 93,100 9,190,000 5,677,000 102,500 10,290,000 6,361,000 111,200 11,379,000 7,039,000
$4535 $4093 $3574 $3096 $2663 $2276 $1939 $1652 $1417 $1235 $1104
(1,700) 22,800 52,300 80,500 107,400 133,000 157,300 180,200 201,600 221,800 240,500
Total number of cases over the lifetime of the cohort discounted at a future rate of 3%.
weighed the risks of vaccination for both adult vaccination strategies (Table 4).
Costs and Cost Effectiveness The societal cost of adult pertussis without a vaccination program over the lifetime of the cohort ranged from $301 million to $9.4 billion, depending on assumptions about disease incidence. A one-time vaccination strategy for adults aged 20 to 64 years would result in 106 million people vaccinated, or approximately 64% of the adult cohort, for a vaccination program cost of $2.1 billion in this cohort. A decennial booster vaccination strategy would result in 335 million immunizations in the adult population for a total program cost of ⬃$6 billion for this cohort. Adult vaccination strategies could prevent considerable medical and nonmedical costs at high incidence rates of pertussis. The net cost of a one-time adult vaccination strategy was $2 billion at low disease incidence and $418 million at
high disease incidence (Table 4). The net cost of a decennial booster strategy ranged from $4.5 billion at low disease incidence to $1.1 billion at high disease incidence. Depending on the incidence assumptions, a one-time adult vaccination strategy ranged from $120 to $29,000 per pertussis case prevented and a decennial booster strategy ranged from $160 to $31,000 per pertussis case prevented (Table 5). At high disease incidence, for example, 500 per 100,000, the cost per QALY saved was $4000 to $5000 for the one-time adult vaccination and decennial booster strategies, respectively. At a low disease incidence of 10 per 100,000, the disutility of vaccine adverse events outweighed the benefit of disease prevention when QALYs were used as the metric of effectiveness. One-time and decennial booster vaccination strategies were less than $50,000 per QALY saved if disease incidence was greater than 120 cases per 100,000. The cost per case prevented and cost per
Table 5. Cost effectiveness of pertussis vaccination of a hypothetical cohort of 166 million adults from the societal perspective One-time adult vaccination program
Decennial adult vaccination program
Incidence (cases per 100,000)
$ per discounted pertussis case preventeda
$ per QALY saved
$ per discounted pertussis case prevented
$ per QALY saved
10 50 100 150 200 250 300 350 400 450 500
$29,000 $5,200 $2,200 $1,300 $830 $560 $390 $280 $210 $130 $120
Dominated $170,000 $65,000 $36,000 $23,000 $16,000 $11,000 $8,000 $6,000 $5,000 $4,000
$31,000 $5,600 $2,500 $1,400 $920 $630 $450 $330 $250 $190 $160
Dominated $179,000 $68,000 $38,000 $25,000 $17,000 $12,000 $9,000 $7,000 $6,000 $5,000
a
Cost and benefits are discounted at a future rate of 3%.
190
American Journal of Preventive Medicine, Volume 32, Number 3
www.ajpm-online.net
Figure 1. Two-way sensitivity analysis of pertussis incidence and incremental vaccine cost for the one-time adult vaccination strategy.
because of pertussis in adults was also examined, and no significant change in cost-effectiveness ratios was found (data not shown). Finally, the potential impact of herd immunity on the cost effectiveness of adult vaccination was considered. As the degree of herd immunity increased, the cost per QALY of adult vaccination strategies decreased. Herd immunity had a greater impact on cost effectiveness when disease incidence was low, suggesting that a certain threshold of cases prevented is needed for the intervention to appear cost effective (Appendix D, online at www.ajpm-online.net). When the time horizon of the analysis was changed to 10 years, there was no difference in cost-effectiveness ratios (data not shown).
Discussion QALY saved were slightly higher for the decennial adult vaccination strategy because of the incrementally higher cost of preventing each additional case of pertussis due to the persistence of low-level immunity after 10 years.
Sensitivity Analyses To understand the impact of severity of disease, vaccine cost, vaccine efficacy, and frequency of vaccine adverse events on the cost effectiveness of adult vaccination programs, alternative analyses were performed. The cost effectiveness ratios did not change appreciably if no adjustment was made for severity of illness, suggesting minimal impact of assuming a similar spectrum of disease severity at high incidence rates identified by active surveillance. An incremental vaccine cost of $5 resulted in a program that was cost effective at incidence rates less than 100 per 100,000 and cost saving at incidence rates higher than 100 per 100,000 (Figure 1). A higher incremental vaccine cost of $35, a lower vaccine efficacy of 50%, or a shorter duration of pertussis illness shifted the curve up so that a costeffectiveness ratio threshold of $50,000 was exceeded unless incidence rates were greater than 175 per 100,000 (Figures 1 and 2; Appendix C, online at www.ajpm-online.net). The results were not significantly affected by the assumption that there were no incremental vaccine adverse events. The only difference in these analyses was that at an incidence rate of 10 per 100,000, adult vaccination strategies had cost-effectiveness ratios of $700,000 to $800,000 per QALY saved instead of being dominated by no vaccination, because there was no disutility associated with vaccination. A dominated strategy is one that is more costly and results in fewer QALYs saved than another strategy. Varying the discount rate also did not significantly affect the cost effectiveness of an adult vaccination program (data not shown). The impact of restructuring the model to include death March 2007
Tdap vaccination for adults aged 20 – 64 years was found to be cost effective if pertussis incidence were at least 120 per 100,000. The range of plausible incidence estimates reported in the literature is broad, and costeffectiveness ratios ranged from $4000 per QALY saved to dominated (more costly and less effective than alternative strategies) as incidence was varied. At the very lowest assumption of disease incidence, the analysis suggested that the risks of vaccination outweighed the benefits. However, using more recent estimates from the literature of an incidence rate of 360 per 100,000, an adult vaccination program is cost effective.12,13 Accurate estimates of pertussis incidence have been difficult to determine because of the under-recognition of adult disease and limitations of currently available diagnostic tests. In addition, pertussis is an endemic disease that historically has epidemic cycles every 3– 4 years, so that incidence estimates must be interpreted within the context of the timing and geographic region. Given that disease incidence is an important driver of the cost effectiveness of an adult vaccination program, it is not surprising that conflicting estimates
Figure 2. Two-way sensitivity analysis of pertussis incidence and vaccine efficacy for the one-time adult vaccination strategy.
Am J Prev Med 2007;32(3)
191
have been reported. A recent review by Cortese et al.13 provides a comprehensive assessment of estimates of adult disease that range from 35 to 368 per 100,000 based on four prospective studies conducted in the U.S. The latest study, which was conducted within the context of a clinical trial with rigorous identification and follow-up of pertussis cases, demonstrated a combined adolescent and adult incidence rate of 368 per 100,000.12 Another study by Strebel et al.13,15 demonstrated a pertussis incidence rate of 361 per 100,000 for adults. Adjustments were made for disease severity by incidence rate in the analysis to evaluate whether the cost effectiveness of a vaccination program remained robust, even if the majority of cases were generally mild. A severity adjustment did not affect the cost effectiveness of an adult vaccination program, which is particularly helpful because decision makers may be concerned about bias in the interpretation of studies that reported high incidence rates. The cost effectiveness of a vaccination program was found to be critically dependent on vaccine cost and vaccine efficacy, which is not surprising. The disutility of vaccine adverse events was also considered in the baseline analysis. At high disease incidence, the benefits of vaccination far outweighed the risk of minor vaccine adverse events. When pertussis incidence was low, the cumulative impact of minor vaccine adverse events over a large population resulted in net worse health, as shown by lower estimates of QALYs saved. Some experts would recommend that minor vaccine adverse events be ignored in this cost effectiveness analysis. However, we believe their inclusion allows for a balanced assessment of the relative risks of both disease and vaccine outcomes. Including the effect of herd immunity in the model was found to modestly improve the cost effectiveness of the program at low disease incidence. Nonetheless, the additional benefit gained from herd immunity did not change the overall interpretation of this analysis, unless disease incidence was close to a threshold of 120 per 100,000. The degree of herd immunity that may result from an adult vaccination programs is unknown, but likely will depend on vaccine delivery rates and contact patterns among members of different age groups who have different risks of pertussis in the population. Further work to assess herd immunity because of adult pertussis vaccination is needed. In conclusion, a Tdap vaccination program in adults aged 20 – 64 years to prevent pertussis is likely to have benefits that outweigh vaccination risks, and is cost effective if the incidence of pertussis is greater than 120 per 100,000 population in this age group. We thank Charles LeBaron and Donna Rusinak for their invaluable contributions to this work. G.M.L. was supported by the Agency for Healthcare Research and Quality, U.S. Department of Health and Human
192
Services (K-08 HS013908-01 A1). Original analyses were funded by the National Immunization Program and Centers for Disease Control and Prevention via cooperative agreement with the Association of Teachers of Preventive Medicine, Task order #TS-0675. This work was presented to the Advisory Committee on Immunization Practices, October 2005, Atlanta GA. No financial conflict of interest was reported by the authors of this paper.
References 1. Farizo KM, Cochi SL, Zell ER, Brink EW, Wassilak SG, Patriarca PA. Epidemiological features of pertussis in the United States, 1980 –1989. Clin Infect Dis 1992;14:708 –19. 2. Yih WK, Lett SM, des Vignes FN, Garrison KM, Sipe PL, Marchant CD. The increasing incidence of pertussis in Massachusetts adolescents and adults, 1989 –1998. J Infect Dis 2000;182:1409 –16. 3. Pertussis—United States, 1997–2000. MMWR Morb Mortal Wkly Rep. 2002;51:73– 6. 4. Black S. Epidemiology of pertussis. Pediatr Infect Dis J 1997;16(4 Suppl):S85–9. 5. Guris D, Strebel PM, Bardenheier B, et al. Changing epidemiology of pertussis in the United States: increasing reported incidence among adolescents and adults, 1990 –1996. Clin Infect Dis 1999;28:1230 –7. 6. De Serres G, Shadmani R, Duval B, et al. Morbidity of pertussis in adolescents and adults. J Infect Dis 2000;182:174 –9. 7. Thomas PF, McIntyre PB, Jalaludin BB. Survey of pertussis morbidity in adults in western Sydney. Med J Aust 2000;173:74 – 6. 8. Lee GM, Lett S, Schauer S, et al. Societal costs and morbidity of pertussis in adolescents and adults. Clin Infect Dis 2004;39:1572– 80. 9. Postels-Multani S, Schmitt HJ, Wirsing von Konig CH, Bock HL, Bogaerts H. Symptoms and complications of pertussis in adults. Infection 1995;23:139 – 42. 10. Purdy KW, Hay JW, Botteman MF, Ward JI. Evaluation of strategies for use of acellular pertussis vaccine in adolescents and adults: a cost– benefit analysis. Clin Infect Dis 2004;39:20 – 8. 11. Lee GM, Lebaron C, Murphy TV, Lett S, Schauer S, Lieu TA. Pertussis in adolescents and adults: should we vaccinate? Pediatrics 2005;115:1675– 84. 12. Ward JI, Cherry JD, Chang SJ, et al. Efficacy of an acellular pertussis vaccine among adolescents and adults. N Engl J Med 2005;353:1555– 63. 13. Cortese MM, Baughman A, Brown K, Srivastava P. A “new age” for pertussis prevention in the United States: seizing opportunities through adult vaccination. Am J Prev Med 2007;32:177– 85. 14. http://www.census.gov/popest/states/NST-ann-est.html. 15. Strebel P, Nordin J, Edwards K, et al. Population-based incidence of pertussis among adolescents and adults, Minnesota, 1995–1996. J Infect Dis 2001;183:1353–9. 16. Nennig ME, Shinefield HR, Edwards KM, Black SB, Fireman BH. Prevalence and incidence of adult pertussis in an urban population. JAMA 1996;275:1672– 4. 17. Mink CM, Cherry JD, Christenson P, et al. A search for Bordetella pertussis infection in university students. Clin Infect Dis 1992;14:464 –71. 18. Centers for Disease Control and Prevention. Pertussis—United States, 1997–2000. JAMA 2002;287:977–9. 19. Ward J. The APERT Study. Paper presented at the National Consensus Conference on Pertussis, May 25–28, 2002, Toronto. 20. Ward JI, APERT Study Group. Pertussis epidemiology and acellular pertussis vaccine efficacy in older children: NIH APERT Multicenter Pertussis Trial. Paper presented at the Pediatric Academic Societies Annual Meeting, 2001, Baltimore MD. 21. Jenkinson D. Duration of effectiveness of pertussis vaccine: evidence from a 10 year community study. Br Med J (Clin Res Ed) 1988;296:612– 4. 22. Lambert HJ. Epidemiology of a small pertussis outbreak in Kent County, Michigan. Public Health Rep 1965;80:365–7. 23. Cattaneo LA, Reed GW, Haase DH, Wills MJ, Edwards KM. The seroepidemiology of Bordetella pertussis infections: a study of persons ages 1– 65 years. J Infect Dis 1996;173:1256 –9. 24. Ramsay ME, Farrington CP, Miller E. Age-specific efficacy of pertussis vaccine during epidemic and non-epidemic periods. Epidemiol Infect 1993;111:41– 8.
American Journal of Preventive Medicine, Volume 32, Number 3
www.ajpm-online.net
25. Gold MR, Siegel JE, Russell LB, Weinstein MC. Cost-effectiveness in health and medicine. New York: Oxford University Press; 1996. 26. Van der Wielen M, Van Damme P, Joossens E, Francois G, Meurice F, Ramalho A. A randomised controlled trial with a diphtheria–tetanus– acellular pertussis (dTap) vaccine in adults. Vaccine 2000;18:2075– 82. 27. Halperin SA, Smith B, Russell M, et al. An adult formulation of a five-component acellular pertussis vaccine combined with diphtheria and tetanus toxoids is safe and immunogenic in adolescents and adults. Vaccine 2000;18:1312–9. 28. Halperin SA, Smith B, Russell M, et al. Adult formulation of a five component acellular pertussis vaccine combined with diphtheria and tetanus toxoids and inactivated poliovirus vaccine is safe and immunogenic in adolescents and adults. Pediatr Infect Dis J 2000;19:276 – 83. 29. Rennels MB. Extensive swelling reactions occurring after booster doses of diphtheria–tetanus–acellular pertussis vaccines. Semin Pediatr Infect Dis 2003;14:196 – 8. 30. Rennels MB, Deloria MA, Pichichero ME, et al. Extensive swelling after booster doses of acellular pertussis–tetanus– diphtheria vaccines. Pediatrics 2000;105:e12. 31. Jackson LA, Carste BA, Malais D, Froeschle J. Retrospective populationbased assessment of medically attended injection site reactions, seizures, allergic responses and febrile episodes after acellular pertussis vaccine combined with diphtheria and tetanus toxoids. Pediatr Infect Dis J 2002;21:781– 6. 32. Bohlke K, Davis RL, Marcy SM, et al. Risk of anaphylaxis after vaccination of children and adolescents. Pediatrics 2003;112:815–20. 33. Singleton JA, Greby SM, Wooten KG, Walker FJ, Strikas R. Influenza, pneumococcal, and tetanus toxoid vaccination of adults—United States, 1993–7. MMWR CDC Surveill Summ 2000;49:39 – 62. 34. Van Rie A, Hethcote HW. Adolescent and adult pertussis vaccination: computer simulations of five new strategies. Vaccine 2004;22:3154 – 65. 35. Deen JL, Mink CA, Cherry JD, et al. Household contact study of Bordetella pertussis infections. Clin Infect Dis 1995;21:1211–9. 36. Crowcroft NS, Booy R, Harrison T, et al. Severe and unrecognised: pertussis in UK infants. Arch Dis Child 2003;88:802– 6. 37. Bisgard KM, Pascual FB, Ehresmann KR, et al. Infant pertussis: who was the source? Pediatr Infect Dis J 2004;23:985–9. 38. Bourgeois F, Goldmann DA, Ross-Degnan D, Hibberd P, Lee GM. Health service utilization and economic burden of daycare-associated illness. Abstract presented at the Pediatric Academic Societies’ Annual Meeting, San Francisco CA, 2006. 39. Centers for Medicare & Medicaid Services (CMS) HHS. Medicare Program: changes to the hospital inpatient prospective payment systems and rates and costs of graduate medical education: fiscal year 2002 rates; Provisions
March 2007
40.
41. 42. 43. 44. 45. 46. 47.
48.
49.
50. 51. 52.
53.
54.
55.
56.
of the Balanced Budget Refinement Act of 1999; and Provisions of the Medicare, Medicaid, and SCHIP Benefits Improvement and Protection Act of 2000: Department of Health and Human Services, Centers for Medicare & Medicaid Services, August 1, 2001. Vol. 66, No. 148, 42 CFR Parts 405, 410, 412. Morris M, Tang S. Pediatric Service Utilization, Fees and Managed Care Arrangements, 2001 report based on 1999 data. Elk Grove Village: American Academy of Pediatrics; 2001. NASA. Available at http://www.jsc.nasa.gov/bu2/inflateGDP.html (Accessed October 30, 2005). U.S. Census Bureau. Available at www.census.gov/hhes/income/ income00/inctab7.html. Arrow Pharmaceuticals. Available at http://www.arrowpharma.com/about. cfm. Aventis Pasteur—Canada, 1-416-667-2700. Bundaberg & District, Division of General Practice. Available at http://www.widebaydgp.org.au/News/newslett/Sept-Oct2002a.pdf. http://www.worldwidevaccines.com/by_country/gsk_vaccines.asp. Zhou W, Pool V, Iskander JK, et al. Surveillance for safety after immunization: vaccine adverse event reporting system (VAERS)—United States, 1991–2001. MMWR Surveill Summ 2003;52:1–24. Lee gm, Salomon JA, LeBaron CW, Lieu TA. Health-state valuations for pertussis: methods for valuing short-term health states. Health Qual Life Outcomes 2005;3:17. Tozzi AE, Rava L, Ciofi degli Atti ML, Salmaso S. Clinical presentation of pertussis in unvaccinated and vaccinated children in the first six years of life. Pediatrics 2003;112:1069 –75. Birkebaek NH, Kristiansen M, Seefeldt T, et al. Bordetella pertussis and chronic cough in adults. Clin Infect Dis 1999;29:1239 – 42. http://www.cdc.gov/nip/vfc/cdc_vac_price_list.htm#adult. Stone PW, Teutsch S, Chapman RH, Bell C, Goldie SJ, Neumann PJ. Cost-utility analyses of clinical preventive services: published ratios, 1976 – 1997. Am J Prev Med 2000;19:15–23. Chapman RH, Stone PW, Sandberg EA, Bell C, Neumann PJ. A comprehensive league table of cost-utility ratios and a sub-table of “panel-worthy” studies. Med Decis Making 2000;20:451– 67. Pignone M, Saha S, Hoerger T, Mandelblatt J. Cost-effectiveness analyses of colorectal cancer screening: a systematic review for the U.S. Preventive Services Task Force. Ann Intern Med 2002;137:96 –104. Winkelmayer WC, Weinstein MC, Mittleman MA, Glynn RJ, Pliskin JS. Health economic evaluations: the special case of end-stage renal disease treatment. Med Decis Making 2002;22:417–30. TreeAge Pro 2005 Suite [computer program]. Version 0.4. Williamstown MA: TreeAge Software, Inc.; 2005.
Am J Prev Med 2007;32(3)
193
Appendix A—Simplified decision tree structure for adult pertussis vaccination
Appendix B—Simplified decision tree structure for infant disease
193.e1
American Journal of Preventive Medicine, Volume 32, Number 3
Incremental cost per QALY
Appendix C—Two-way sensitivity analysis of pertussis incidence and duration of pertussis health states for the one-time adult vaccination strategy
44 days
87 days (baseline)
174 days
$200,000 $150,000 $100,000 $50,000 $0 0
100
200
300
400
500
Incidence per 100,000 Appendix D—Impact of herd immunity on the cost effectiveness of a decennial booster strategy
Incremental cost per QALY
Baseline 0%
Herd 15%
Herd 30%
Herd 45%
$200,000 $150,000 $100,000 $50,000 $0
100
200
300
400
500
Incidence (per 100,000)
Am J Prev Med 2007;32(3)
193.e2