Determining the Optimal Vaccination Schedule for Herpes Zoster: a Cost-Effectiveness Analysis
KEY WORDS: herpes zoster; cost-effectiveness; booster.
J Gen Intern Med
Determining the Optimal Vaccination Schedule for Herpes Zoster: a Cost-Effectiveness Analysis
Phuc Le 0
Michael B. Rothberg 0
0 Center for Value-Based Care Research, Medicine Institute, Cleveland Clinic , Cleveland, OH , USA
BACKGROUND: The Advisory Committee on Immunization Practices recommends a single dose of herpes zoster (HZ) vaccine in persons aged 60 years or older, but the efficacy decreases to zero after approximately 10 years. A booster dose administered after 10 years might extend protection, but the cost-effectiveness of a booster strategy has not been examined. OBJECTIVE: We aimed to determine the optimal schedule for HZ vaccine DESIGN: We built a Markov model to follow patients over their lifetime. From the societal perspective, we compared costs and quality-adjusted life years (QALYs) saved of 11 strategies to start and repeat HZ vaccine at different ages. SUBJECTS: Adults aged 60 years. INTERVENTION: HZ vaccine. MAIN MEASURES: Costs, quality-adjusted life years (QALYs), and incremental costs per QALY saved. KEY RESULTS: At a $100,000/QALY threshold, “vaccination at 70 plus one booster” was the most cost-effective strategy, with an incremental cost-effectiveness ratio (ICER) of $36,648/QALY. “Vaccination at 60 plus two boosters” was more effective, but had an ICER of $153,734/QALY. In deterministic sensitivity analysis, “vaccination at 60 plus two boosters” cost < $100,000/ QALY if compliance rate was > 67 % or vaccine cost was < $156 per dose. In probabilistic sensitivity analysis, “vaccination at 70 plus one booster” was preferred at a willingness-to-pay of up to $135,000/QALY. CONCLUSIONS: Under current assumptions, initiating HZ vaccine at age 70 years with one booster dose 10 years later appears optimal. Future data regarding compliance with or efficacy of a booster could affect these conclusions.
Herpes zoster (HZ) is a painful dermatomal vesicular rash
afflicting almost one in three adults.1 Of the approximately
one million Americans who experience HZ annually, 8–32 %
develop postherpetic neuralgia (PHN), an often debilitating
pain persisting greater than 3 months.2 The frequency and
severity of HZ and PHN increase with age, especially after
50 years.1 Because antiviral therapy has limited effectiveness,
efforts have focused on prevention.3
The live attenuated Oka strain VZV vaccine reduces the
incidence of HZ, PHN and their associated burden-of-illness
(BOI) among people ≥ 50 years of age,4–7 but the Advisory
Committee on Immunization Practices (ACIP) recommends
the vaccine only for adults aged ≥ 60 years,8 in part because
the vaccine appears not to be cost-effective below this age.9 For
adults younger than 60 years, this policy is a de facto
recommendation to be vaccinated on turning 60 years. Because
vaccine efficacy declines to zero over approximately 10 years,4 the
current recommendation could leave adults lacking protection
after age 70, when PHN is most prevalent. A booster dose
administered after 10 years might extend protection, but the
cost-effectiveness of a booster strategy has not been examined.
Recently, a clinical trial assessed the safety and
immunogenicity of a 10-year booster dose administered to adults aged
≥70 years and found it to be safe and to produce antibody
responses similar to those of patients vaccinated for the first
time.10 The discovery of waning immunity and the possibility
of one or more booster doses add complexity to the decision
about when to vaccinate. Early vaccination with one or more
boosters should be most effective, but could be expensive.
Waiting to vaccinate until rates of HZ and PHN begin to rise
might prevent a substantial proportion of disease at lower cost.
We used a Markov decision model to examine the
costeffectiveness of competing vaccination schedules
incorporating new data on vaccine persistence,4 and safety and
immunogenicity of a booster dose.10
We updated a previously published Markov model9, 11 (online
Appendix Figure 1) and compared the cost-effectiveness of 11
strategies: no vaccination, one-time vaccination at 5-year
intervals from 60 to 80 years, vaccination at 5-year intervals
from 60 to 75 years with a booster after 10 years, and
vaccination at 60 years with two boosters 10 years apart. The entire
cohort entered the model at age 60 and was followed for a
lifelong time horizon (or to age 120) with a Markov-cycle length
of 1 year. People could receive no vaccine or one of the
HZ incidence/1000 person-yearsa
Age ≥ 80
Age ≥ 80
PHN given HZ
Age ≥ 70
PHN from 6 to 12 months
PHN ≥ 12 months
Age < 70
Age ≥ 70
Any ophthalmic complications
Monocular blindness, given ophthalmic complications
Monaural deafness, given herpes oticus
Hospitalization given HZ
Death due to HZ, per 1,000,000 cases
Age ≥ 90
Duration of HZ hospitalization, mean days
Vaccine efficacy against HZ incidence (%)
Initial efficacy at vaccination
Annual waning rate
Likelihood ratio, by age
Age ≥ 85
Vaccine efficacy against BOI (%)
Initial efficacy at vaccination
Annual waning rate
Vaccine efficacy against PHN incidence (%)
Efficacy for the first 5 years
Annual waning rate from year 6
Post herpetic neuralgia after 6 months
Short term morbidities (QALYs)
Acute herpes zoster
Direct medical costs, $ per case
Hospitalization for HZ
*Although vaccine price is variable, it is determined by the manufacturer and not uncertain. Therefore, we did not define a probabilistic distribution for
†Ranges for one-way sensitivity analysis generally represent 95 % confidence intervals, except for costs, where wider ranges were tested
‡Because the compliance rate is unknown, the range is from 0 to 1
§ For model inputs with age-specific values, the distribution was first defined for the lowest age group, which was considered as the reference.
Distributions for remaining age groups were determined by multiplying relative likelihood ratios among these ages and the reference age by the
reference distribution. Because the value was drawn randomly from the distribution in PSA, this definition of distributions ensured that the probabilistic
values of different age groups had the appropriate relative magnitudes compared with one another as when they were deterministic.9
HZ herpes zoster, PHN postherpetic neuralgia, BOI burden-of-illness, QALY quality-adjusted life year, PSA probabilistic sensitivity analysis, NA not
strategies described above. For all strategies, people began in
the “Healthy” state and moved to other health states according
to transition probabilities (Table 1). Following each HZ
episode, the patient could die, fully recover or experience
Compared to the unvaccinated group, vaccinated patients
had a reduction in disease incidence and complications
proportional to vaccine efficacy, which waned over time.
Following a booster, vaccine efficacy increased and then waned at the
same rate as following initial vaccination. Model inputs were
derived from the medical literature. Model outputs, including
costs (vaccine and disease treatment costs) and outcomes (the
number of HZ cases, PHN cases, and quality-adjusted life
years or QALYs), were computed for each strategy. Based
on the mid-range of the World Health Organization
recommendation,27 we chose $100,000/QALY as the
costeffectiveness threshold. The study was conducted from the
societal perspective. Costs and QALYs were discounted at
3 %. Costs were expressed in 2014 US dollars. The medical
care component of the Consumer Price Index was used to
adjust for inflation.28 We developed the model in TreeAge
Pro 2014 (TreeAge Software, Williamstown, MA).
Model Inputs and Assumptions
Estimates and ranges for the base-case and sensitivity analyses
are presented in Table 1. Important inputs are described below.
Epidemiologic Parameters. The incidence of HZ began rising
before varicella vaccine was introduced.1, 12, 29 It could represent
better reporting, lack of natural boosting from exposure to
chicken pox, or other factors. To estimate this increasing rate,
we fit several linear regressions using the sex-specific incidences
for people aged ≥ 65 during 1993–2006, as reported in the most
comprehensive observational study of increasing HZ
incidence.12 We then took the age- and sex-specific incidence from
the largest HZ study in the U.S.13 as the baseline and applied the
regression slopes to project incidences for 2010 (the latest year of
rising incidence). We assumed incidence then remained stable
because varicella vaccination has been implemented universally
for 15 years30 and advertising for Zostavax had raised general
awareness. Moreover, our projected incidence for 2010 exceeded
carefully adjudicated incidence among unvaccinated controls
Age-specific incidence of PHN, defined as HZ pain
persisting ≥ 3 months, was based on the Shingles Prevention Study
(SPS).5 Age-specific HZ hospitalization rates were modeled
on a large managed care organization.16 HZ age-specific
mortality rates were drawn from the CDC.17 Estimates and
derivations of other complications have been described
previously.11 We used the 2010 US life tables to derive background
age- and sex-specific mortality.32 The sex distribution
reflected the 2013 US population.33
Vaccine-Related Parameters. The SPS, a randomized trial of
the live attenuated HZ vaccine, reported efficacy up to 4 years
post-vaccination.5 After its completion, a subset of
participants was re-enrolled for the Short-term Persistence Substudy
(STPS),7 which reported efficacy up to 7 years
postvaccination. The Long-term Persistence Substudy (LTPS)
reported efficacy from 7 to 11 years post-vaccination.4
The SPS, STPS, and LTPS reported three efficacy end
points: BOI, PHN incidence, and HZ incidence.4, 5, 7 BOI
measured total pain from HZ for 182 days after disease onset.
Efficacy for BOI was reported for the whole population, most of
whom had a BOI of zero. It therefore incorporated the vaccine’s
impact on HZ incidence, as well as severity of pain from either
HZ or PHN in the first 6 months. Efficacy against HZ and PHN
incidence was also reported for the entire population. In order to
separate these different vaccine effects, we first estimated the
efficacy for HZ incidence by year since vaccination. We then
estimated the additional efficacies for BOI and PHN incidence
among HZ cases by developing an equation to describe the
relationship between the efficacy for HZ incidence and the
overall efficacy for BOI or PHN incidence of the entire
population (see online Appendix). The efficacy function for HZ
incidence was: y = – 0.0544 × year + 0.6478, for BOI: y =
– 0.0437 × year 0.7083, and for PHN incidence: y – 0.1 ×
year + 1.218 (online Appendix Figure 2). Initial efficacy
against HZ incidence was further adjusted for vaccination
age using age-specific likelihood ratios calculated from the
A recent study showed that a booster administered after ≥
10 years had similar safety and immunogenicity as a first dose
among people ≥70 years.10 We assumed that a booster dose
would have the same efficacy as an initial dose administered at
Compliance with multi-dose vaccine schedules varies by
vaccine, but is consistently low among all age groups.34–36 In
our base-case, we assumed 60 % compliance (i.e., the
percentage of patients who would receive a booster), based on older
adults’ compliance with tetanus boosters.19
QALYs. Utility estimates have been described previously.11
QALY loss due to HZ was estimated using the average BOI
scores from SPS. The scores were transformed into utilities
based on a study that reported both BOI scores and
EuroQOL5D utilities.23 The utility of PHN beyond 6 months was based
on the work of Edmunds et al.21 We assumed serious vaccine
reactions represented allergic reactions and resulted in
hospitalization with a utility of zero. Length of stay was based on
hospitalizations for allergic reactions.18 Utilities were adjusted
Costs. We derived costs from various sources. We used the
CDC’s private sector vaccine price.24 Vaccine administration
was based on the Medicare rate.25 Serious reactions were
assumed to cost the same as allergic reactions requiring
hospitalization.18 Local reactions were minimal and assumed
not to incur costs. Direct medical costs for treatment of acute
HZ, PHN, ocular complications, and herpes oticus were based
on our previous study.11 Productivity loss due to HZ was
estimated as described previously,9 and age-adjusted to reflect
the percentage of people in the labor force.38 The 2012 Health
Care Utilization Project was used to estimate the length of stay
and hospitalization costs (ICD-9-CM codes 053.0–053.9 for
HZ and 995.27 for allergic reactions).18
One-Way Sensitivity Analysis. We conducted one-way
sensitivity analysis to examine the effect of all epidemiologic,
vaccine-related and utility parameters on the
cost–effectiveness of vaccination strategies.
Two-Way Sensitivity Analysis. We conducted two-way
sensitivity analysis by varying the initial efficacy against HZ
incidence and its annual waning rate, and vaccine cost against
compliance rate. Finally, we varied vaccine cost and the initial
efficacy against HZ incidence.
Probabilistic Sensitivity Analysis. We employed 10,000
iterations of Monte Carlo simulation simultaneous varying
all model inputs. We displayed the results as a
costeffectiveness acceptability curve showing the percentage of
iterations that each strategy had an ICER below a specific
willingness-to-pay (WTP) threshold.
We validated our model by summing the annual cases of HZ and
PHN, and BOI scores in the vaccinated and non-vaccinated
groups, and then calculating the vaccine efficacy for time periods
corresponding to the SPS, STPS, and LTPS.4, 5, 7 Due to the lack
of detailed information on sex distribution by age of SPS
participants, we applied the overall sex distribution equally across age
groups and estimated efficacy for people aged 60 and 70 years
separately. We then weighted the efficacy by age distribution for
60–69 and ≥ 70 years to reflect that of the SPS.
Modeled efficacies for HZ incidence, PHN incidence, and
BOI were very close (within 1–3 percentage points) to those
reported in the trials (online Appendix Table 1).
*This strategy has higher ICER than the next more effective strategy
† This strategy has higher cost than the next more effective strategy
ICER Incremental cost-effectiveness ratio
cination strategies. All but four strategies were
dominated. No vaccination had the lowest cost and produced the
fewest QALYs. “Vaccination at 60 plus two boosters”
provided the greatest number of QALYs, but with an
ICER of $153,734/QALY. At a willingness to pay of
$100,000/QALY, “vaccination at 70 years plus one
booster” provided the most QALYs and was highly
cost-effective with an ICER of $36,648/QALY.
and QALYs gained per 1000 vaccinated persons for each
strategy compared to no vaccination. If no booster was
available, “vaccination at 70” prevented more cases and produced
more QALYs. Adding a booster after 10 years was always
more effective than one-time vaccination at the same age.
Finally, “vaccination at 60 plus two boosters” prevented the
most cases and produced the most QALYs.
One-Way Sensitivity Analysis. Within the plausible parameter
ranges for all variables, the four non–dominated strategies and
their ordering did not change. Figure 2 displays all inputs that
changed the ICER of “vaccination at 60 plus two boosters” by
>10 %. “Vaccination at 60 plus two boosters” would be the
most cost-effective strategy at $100,000/QALY if compliance
rate was > 67 %, QALYs lost due to HZ was equal to the lower
bound of the 95 % CI, vaccine cost was < $156/dose, initial
vaccine efficacy against HZ incidence was > 69.2 %, waning
rate of efficacy against HZ incidence was < 4.5 %/year, or
probability of having a serious vaccine reaction was < 0.27 %.
Two-Way Sensitivity Analysis. We found that “vaccination at
60 plus two boosters” was preferred at a threshold of
$100,000/QALY if initial vaccine efficacy was high and the
rate of decline was low (Fig. 3-a). At a higher compliance rate,
Figure 3. Two-way sensitivity analysis of impact of different
combinations of variables using a willingness-to-pay threshold of
$100,000/quality-adjusted life year gained. Letter X denotes
basecase. a Initial efficacy at vaccination and annual waning rate of the
efficacy against herpes zoster incidence. b Vaccine cost and
compliance rate. c Vaccine cost and the initial efficacy against herpes
zoster incidence at vaccination.
“vaccination at 60 plus two boosters” was preferred unless the
vaccine cost was high (Fig. 3-b). Finally, the lower the vaccine
cost and the higher the initial efficacy against HZ incidence,
the more cost-effective the “vaccination at 60 plus two
boosters” was (Fig. 3-c).
Probabilistic Sensitivity Analysis. Figure 4 shows the
probability of each strategy being preferred (i.e., offering the
greatest number of QALYs) at different WTP thresholds.
Between $40,000/QALY – $135,000/QALY, “vaccination at
70 plus one booster” was most likely to be preferred. At
$100,000/QALY threshold, “vaccination at 60 plus two
boosters” had only 35 % probability of being preferred.
Recent information about waning efficacy of HZ vaccine, as
well as the safety and immunogenicity of a booster, raise
questions regarding the optimal age to vaccinate and whether
a booster dose is cost-effective. We used a decision analytic
model that incorporated these new data to compare the lifetime
benefit and cost-effectiveness of administering first-time
vaccination and boosters at different ages. Assuming a WTP
threshold of $100,000/QALY, we found “vaccination at 70
plus one booster” to be the optimal immunization schedule.
Vaccinating earlier prevented more cases of HZ, but avoided
fewer cases of PHN due to a lower PHN incidence at younger
ages. Because PHN has more impact on quality of life, later
vaccination and boosting produced more QALYs. However,
waiting too long produced fewer QALYs because patients
were unprotected during high incidence years prior to
Although “vaccination at 60 plus two boosters” prevented
the most cases, it was very expensive and not cost-effective
under base-case assumptions. However, if the vaccine were to
cost < $156/dose or if > 67 % of patients received a booster
dose, then “vaccination at 60 years plus two boosters” would
cost < $100,000/QALY. Using our best estimates for these
values, and varying all model inputs simultaneously,
“vaccination at 60 plus two boosters” had only a 35 % chance of
being cost-effective. “Vaccination at 70 plus one booster” was
always the most likely to be cost-effective within the WTP
range of $40,000/QALY and $135,000/QALY.
In agreement with previous analyses,39–42 our study
confirmed that if a one-time vaccination (as currently
recommended) were being considered, vaccination at age 70 would be
optimal. Moreover, our study highlights the unintended
consequence of offering one-time vaccination at age 60. Because
of waning immunity, patients vaccinated at age 60 receive
42 % less lifetime protection against PHN than those
vaccinated at 70.
In 2015, a new adjuvanted subunit HZ vaccine (HZ/su) was
demonstrated to prevent 97 % of HZ cases over 3 years.31
Although the duration of protection is unknown, the licensing
of HZ/su vaccine (expected in late 2016) should change the
HZ vaccination paradigm. Based on our sensitivity analysis,
given the new vaccine’s efficacy, “vaccination at 60 plus two
boosters” would be the optimal strategy if the vaccine cost ≤
$388 for the two-dose regimen. However, until the vaccine is
licensed, the cost will not be known. In addition, 96 % of
patients in the randomized trial received both doses.31 Other
two-dose series, such as hepatitis A vaccine, have completion
rates closer to 65 %.34 Thus the new vaccine’s effectiveness
may be substantially lower than in the trial, and vaccination
beginning at 70 years may still be preferred.
Our study has limitations. First, several variables relating to
the booster are unknown. While it is reasonable to assume the
booster will cost the same as initial vaccination, it will be years
before we determine the booster’s efficacy and compliance
rate. Second, efficacy of HZ vaccine was based on the LTPS,
an observational study using historical controls.4 Additional
long-term trials are unlikely. Third, we assumed that the
incidence of HZ stopped rising after 2010 because we could not
assume an unlimited upward trajectory. Carefully adjudicated
events from the recent vaccine study suggest our rates may be
too high,31 but even a continued increase in incidence would
not change the optimal vaccine schedule. Finally, we lacked
contemporary estimates of costs associated with HZ and PHN;
consequently, we inflated previous estimates to 2014 dollars,
but our findings were insensitive to these costs.
Our study appears to be the first to incorporate trial data
regarding long-term efficacy and persistence4 and the first
U.S. study to address cost-effectiveness of vaccination
strategies that include boosters. Our findings have
important implications. The current ACIP recommendation is to
administer one dose of vaccine to patients aged ≥ 60 years.
However, because efficacy beyond 10 years is limited,
vaccination at age 60 appears to be one of the most
expensive and least effective strategies. Based on our model,
delaying vaccination by 10 years should reduce costs while
improving outcomes. Adding a booster dose after 10 years
should offer additional gains at reasonable cost. For patients
who can afford it, beginning vaccination at age 60 followed
by two booster doses 10 years apart would be most
effective, but at a price which cannot be universally advocated.
One potential exception would be if the compliance with the
booster exceeded 67 %, then beginning vaccination at age
60 could be considered cost-effective. However, older
adults’ compliance with a tetanus booster, which also has
a 10-year interval, remains at 60 %.19
In light of the data on waning efficacy, the ACIP may want
to reconsider their recommendation. For patients already
vaccinated, a booster appears to be in order. However, future
vaccination efforts will likely have to be divided between
delivering the initial vaccination and encouraging patients to
get boosters. Following approval of HZ vaccine, uptake has
been slow, hampered by high cost, vaccine shortages and lack
of familiarity.43, 44 Although vaccination rates have begun to
rise,19 the impact of a booster recommendation on vaccine
supply and initial vaccination rates is unknown. One way to
mitigate between these competing needs would be to focus on
vaccinating all patients above age 70, whether they are
unvaccinated or have been vaccinated at least 10 years ago. By
simply not vaccinating patients in their 60s, physicians would
ensure that all remaining strategies were cost-effective.
Following several years of widespread booster use, we should be
able to determine the booster’s effectiveness and compliance
rate. We will also have data on the cost and effectiveness of the
adjuvanted subunit vaccine. At that time, it may be appropriate
to revisit the recommendations. In the interim, current
recommendations appear to be the least effective, and unnecessarily
Acknowledgments: The study was conducted without external
funding. The manuscript was presented at the Society of General
Internal Medicine Annual Meeting, held on May 11–14, 2016 in
Corresponding Author: Phuc Le, PhD, MPH; Center for Value-Based
Care Research, Medicine InstituteCleveland Clinic, Cleveland, OH,
USA (e-mail: ).
Compliance with Ethical Standards:
Conflict of Interest: The authors declare that they do not have a
conflict of interest.
1. Yawn BP , Saddier P , Wollan PC , St Sauver JL , Kurland MJ , Sy LS . A population-based study of the incidence and complication rates of herpes zoster before zoster vaccine introduction . Mayo Clin Proc . 2007 ; 82 ( 11 ): 1341 - 9 .
2. Kawai K , Gebremeskel BG , Acosta CJ . Systematic review of incidence and complications of herpes zoster: towards a global perspective . BMJ Open . 2014 ; 4 ( 6 ), e004833 .
3. Jackson JL , Gibbons R , Meyer G , Inouye L. The effect of treating herpes zoster with oral acyclovir in preventing postherpetic neuralgia. A metaanalysis . Arch Intern Med . 1997 ; 157 ( 8 ): 909 - 12 .
4. Morrison VA , Johnson GR , Schmader KE , Levin MJ , Zhang JH , Looney DJ , et al. Long-term persistence of zoster vaccine efficacy . Clin Infect Dis . 2015 ; 60 ( 6 ): 900 - 9 .
5. Oxman MN , Levin MJ , Johnson GR , Schmader KE , Straus SE , Gelb LD , et al. A vaccine to prevent herpes zoster and postherpetic neuralgia in older adults . N Engl J Med . 2005 ; 352 ( 22 ): 2271 - 84 .
6. Schmader KE , Levin MJ , Gnann JW Jr, McNeil SA , Vesikari T , Betts RF , et al. Efficacy, safety, and tolerability of herpes zoster vaccine in persons aged 50-59 years . Clin Infect Dis . 2012 ; 54 ( 7 ): 922 - 8 .
7. Schmader KE , Oxman MN , Levin MJ , Johnson G , Zhang JH , Betts R , et al. Persistence of the efficacy of zoster vaccine in the shingles prevention study and the short-term persistence substudy . Clin Infect Dis . 2012 ; 55 ( 10 ): 1320 - 8 .
8. Hales CM , Harpaz R , Ortega-Sanchez I , Bialek SR . Update on recommendations for use of herpes zoster vaccine . MMWR Morb Mortal Wkly Rep . 2014 ; 63 ( 33 ): 729 - 31 .
9. Le P , Rothberg MB . Cost-effectiveness of herpes zoster vaccine for persons aged 50 years . Ann Intern Med . 2015 ; 163 ( 7 ): 489 - 97 .
10. Levin MJ , Schmader KE , Pang L , Williams-Diaz A , Zerbe G , Canniff J , et al. Administration of a second dose of herpes zoster vaccine ten years after a first dose . J Infect Dis . 2015 .
11. Rothberg MB , Virapongse A , Smith KJ . Cost-effectiveness of a vaccine to prevent herpes zoster and postherpetic neuralgia in older adults . Clin Infect Dis . 2007 ; 44 ( 10 ): 1280 - 8 .
12. Leung J , Harpaz R , Molinari NA , Jumaan A , Zhou F . Herpes zoster incidence among insured persons in the United States, 1993 - 2006 : evaluation of impact of varicella vaccination . Clin Infect Dis . 2011 ; 52 ( 3 ): 332 - 40 .
13. Insinga RP , Itzler RF , Pellissier JM , Saddier P , Nikas AA . The incidence of herpes zoster in a United States administrative database . J Gen Intern Med . 2005 ; 20 ( 8 ): 748 - 53 .
14. Bouhassira D , Chassany O , Gaillat J , Hanslik T , Launay O , Mann C , et al. Patient perspective on herpes zoster and its complications: an observational prospective study in patients aged over 50 years in general practice . Pain . 2012 ; 153 ( 2 ): 342 - 9 .
15. Helgason S , Petursson G , Gudmundsson S , Sigurdsson JA . Prevalence of postherpetic neuralgia after a first episode of herpes zoster: prospective study with long term follow up . BMJ . 2000 ; 321 ( 7264 ): 794 - 6 .
16. Jackson LA , Reynolds MA , Harpaz R . Hospitalizations to treat herpes zoster in older adults: causes and validated rates . Clin Infect Dis . 2008 ; 47 ( 6 ): 754 - 9 .
17. Centers for Disease Control and Prevention, National Center for Health Statistics . Compressed Mortality File 1999 -2012 on CDC WONDER Online Database , released October 2014 . Data are from the Compressed Mortality File 1999 -2012 Series 20 No. 2R , 2014 , as compiled from data provided by the 57 vital statistics jurisdictions through the Vital Statistics Cooperative Program . Available at: http://wonder.cdc. gov/cmf-icd10.html. Accessed 19 July 2016 .
18. Agency for Healthcare Research and Quality. Healthcare cost and utilization project-HCUP . Available at http://hcupnet.ahrq.gov/HCUPnet.jsp Accessed 19 July 2016 .
19. Williams WW , Lu PJ , O'Halloran A , Bridges CB , Kim DK , Pilishvili T , et al. Vaccination coverage among adults, excluding influenza vaccination - United States , 2013 . MMWR Morb Mortal Wkly Rep . 2015 ; 64 ( 4 ): 95 - 102 .
20. Zoster vaccine live (Oka/Merck) Zostavax. FDA clinical briefing document for Merck and Co ., 2005 [Internet]. Available at: http://www.fda.gov/ ohrms/dockets/ac/05/briefing/5-4198b2_ 1 .pdf. Accessed on 19 July 2016 .
21. Edmunds WJ , Brisson M , Rose JD . The epidemiology of herpes zoster and potential cost-effectiveness of vaccination in England and Wales . Vaccine. 2001 ; 19 ( 23 -24): 3076 - 90 .
22. Hornberger J , Robertus K . Cost-effectiveness of a vaccine to prevent herpes zoster and postherpetic neuralgia in older adults . Ann Intern Med . 2006 ; 145 ( 5 ): 317 - 25 .
23. Coplan PM , Schmader K , Nikas A , Chan IS , Choo P , Levin MJ , et al. Development of a measure of the burden of pain due to herpes zoster and postherpetic neuralgia for prevention trials: adaptation of the brief pain inventory . J Pain . 2004 ; 5 ( 6 ): 344 - 56 .
24. Centers for Disease Control and Prevention. Adult vaccine price list . Available at: http://www.cdc.gov/vaccines/programs/vfc/awardees/vaccine-management/price-list/. Accessed 29 July 2016 .
25. Centers for Medicare and Medicaid services . Physician Fee Schedule . Available at: http://www.cms.gov/apps/physician-fee-schedule/search/search-results. aspx?Y=0&T=0&HT=0&CT=3&H1=90471&M=5. Accessed 19 July 2016 .
26. Briggs AH , Goeree R , Blackhouse G , O'Brien BJ . Probabilistic analysis of cost-effectiveness models: choosing between treatment strategies for gastroesophageal reflux disease . Med Decis Making . 2002 ; 22 ( 4 ): 290 - 308 .
27. WHO-CHOICE . Choosing interventions that are cost-effective . [Internet]. Available at: http://www.who. int/choice/en. Accessed 19 July 2016 .
28. Bureau of Labor Statistic. Medical care component of the Consumer Price Index-All urban consumers . Available at: http://data.bls.gov/cgi-bin / surveymost. Accessed 19 July 2016 .
29. Hales CM , Harpaz R , Joesoef MR , Bialek SR . Examination of links between herpes zoster incidence and childhood varicella vaccination . Ann Intern Med . 2013 ; 159 ( 11 ): 739 - 45 .
30. Marin M , Guris D , Chaves SS , Schmid S , Seward JF , Advisory Committee on Immunization Practices, Centers for Disease Control and Prevention (CDC). Prevention of varicella: recommendations of the Advisory Committee on Immunization Practices (ACIP) . MMWR Recomm Rep . 2007 ; 56 (RR-4): 1 - 40 .
31. Lal H , Cunningham AL , Godeaux O , Chlibek R , Diez-Domingo J , Hwang SJ , et al. Efficacy of an adjuvanted herpes zoster subunit vaccine in older adults . N Engl J Med . 2015 ; 372 ( 22 ): 2087 - 96 .
32. Arias E . United States life tables, 2010. Natl Vital Stat Rep . 2014 ; 63 ( 7 ): 1 - 63 .
33. U.S. Census Bureau , Population Division . Annual Estimates of the Resident Population by Single Year of Age and Sex for the United States: April 1, 2010 to July 1, 2013 . Release Date: June 2014 . Available at: http://factfinder.census.gov/faces/tableservices/jsf/ pages/productview.xhtml?src=bkmk. Accessed 19 July 2016 .
34. Nelson JC , Bittner RC , Bounds L , Zhao S , Baggs J , Donahue JG , et al. Compliance with multiple-dose vaccine schedules among older children, adolescents, and adults: results from a vaccine safety datalink study . Am J Public Health . 2009 ; 99 ( Suppl 2 ): S389 - 97 .
35. Luman ET , Shaw KM , Stokley SK . Compliance with vaccination recommendations for U.S. children . Am J Prev Med . 2008 ; 34 ( 6 ): 463 - 70 .
36. Widdice LE , Bernstein DI , Leonard AC , Marsolo KA , Kahn JA . Adherence to the HPV vaccine dosing intervals and factors associated with completion of 3 doses . Pediatrics. 2011 ; 127 ( 1 ): 77 - 84 .
37. Hanmer J , Lawrence WF , Anderson JP , Kaplan RM , Fryback DG . Report of nationally representative values for the noninstitutionalized US adult population for 7 health-related quality-of-life scores . Med Decis Making . 2006 ; 26 ( 4 ): 391 - 400 .
38. Labor Force Statistics from the Current Population Survey-Employment status of the civilian noninstitutional population by age, sex , and race [Internet]. Available at: http://www.bls.gov/web/empsit/cpseea13.htm . Accessed 29 July 2016 .
39. Pellissier JM , Brisson M , Levin MJ . Evaluation of the cost-effectiveness in the United States of a vaccine to prevent herpes zoster and postherpetic neuralgia in older adults . Vaccine . 2007 ; 25 ( 49 ): 8326 - 37 .
40. Ultsch B , Weidemann F , Reinhold T , Siedler A , Krause G , Wichmann O . Health economic evaluation of vaccination strategies for the prevention of herpes zoster and postherpetic neuralgia in Germany . BMC Health Serv Res . 2013 ; 13 : 359 .
41. Bilcke J , Marais C , Ogunjimi B , Willem L , Hens N , Beutels P . Costeffectiveness of vaccination against herpes zoster in adults aged over 60 years in Belgium . Vaccine. 2012 ; 30 ( 3 ): 675 - 84 .
42. Ortega-Sanchez IR . Decision and cost-effectiveness analyses of herpes zoster vaccination in adults 50 years of age and older [Presentation] . Atlanta, GA: US Department of Health and Human Services , CDC; 2013 .
43. Hurley LP , Lindley MC , Harpaz R , Stokley S , Daley MF , Crane LA , et al. Barriers to the use of herpes zoster vaccine . Ann Intern Med . 2010 ; 152 ( 9 ): 555 - 60 .
44. Lu PJ , Euler GL , Jumaan AO , Harpaz R . Herpes zoster vaccination among adults aged 60 years or older in the United States, 2007: uptake of the first new vaccine to target seniors . Vaccine . 2009 ; 27 ( 6 ): 882 - 7 .