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Original Research |

Cost-Effectiveness of Herpes Zoster Vaccine for Persons Aged 50 YearsCost-Effectiveness of Herpes Zoster Vaccine for Persons Aged 50 Years

Phuc Le, PhD, MPH; and Michael B. Rothberg, MD, MPH
[+] Article, Author, and Disclosure Information

This article was published online first at www.annals.org on 8 September 2015.


From Cleveland Clinic, Cleveland, Ohio.

Disclosures: Authors have disclosed no conflicts of interest. Forms can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M15-0093.

Editors' Disclosures: Christine Laine, MD, MPH, Editor in Chief, reports that she has no financial relationships or interests to disclose. Darren B. Taichman, MD, PhD, Executive Deputy Editor, reports that he has no financial relationships or interests to disclose. Cynthia D. Mulrow, MD, MSc, Senior Deputy Editor, reports that she has no relationships or interests to disclose. Deborah Cotton, MD, MPH, Deputy Editor, reports that she has no financial relationships or interest to disclose. Jaya K. Rao, MD, MHS, Deputy Editor, reports that she has stock holdings/options in Eli Lilly and Pfizer. Sankey V. Williams, MD, Deputy Editor, reports that he has no financial relationships or interests to disclose. Catharine B. Stack, PhD, MS, Deputy Editor for Statistics, reports that she has stock holdings in Pfizer.

Reproducible Research Statement:Study protocol: Not applicable. Statistical code: Availability is subject to discussion with the authors. Please contact Dr. Le (e-mail, lep@ccf.org). Data set: Model inputs and sources are explained in the text.

Requests for Single Reprints: Phuc Le, PhD, MPH, Center for Value-Based Care Research, Medicine Institute, Cleveland Clinic, 9500 Euclid Avenue, Mail Code G10, Cleveland, OH 44195; e-mail, lep@ccf.org.

Current Author Addresses: Drs. Le and Rothberg: Center for Value-Based Care Research, Medicine Institute, Cleveland Clinic, 9500 Euclid Avenue, Mail Code G10, Cleveland, OH 44195.

Author Contributions: Conception and design: P. Le, M.B. Rothberg.

Analysis and interpretation of the data: P. Le, M.B. Rothberg.

Drafting of the article: P. Le.

Critical revision of the article for important intellectual content: P. Le, M.B. Rothberg.

Final approval of the article: P. Le, M.B. Rothberg.

Statistical expertise: P. Le, M.B. Rothberg.

Collection and assembly of data: P. Le, M.B. Rothberg.


Ann Intern Med. 2015;163(7):489-497. doi:10.7326/M15-0093
Text Size: A A A

Background: Each year, herpes zoster (HZ) affects 1 million U.S. adults, many of whom develop postherpetic neuralgia (PHN). Zoster vaccine is licensed for persons aged 50 years or older, but its cost-effectiveness for those aged 50 to 59 years is unknown.

Objective: To estimate the cost-effectiveness of HZ vaccine versus no vaccination.

Design: Markov model.

Data Sources: Medical literature.

Target Population: Adults aged 50 years.

Time Horizon: Lifetime.

Perspective: Societal.

Intervention: HZ vaccine.

Outcome Measures: Number of HZ and PHN cases prevented and incremental cost per quality-adjusted life-year (QALY) saved.

Results of Base-Case Analysis: For every 1000 persons receiving the vaccine at age 50 years, 25 HZ cases and 1 PHN case could be prevented. The incremental cost-effectiveness ratio (ICER) for HZ vaccine versus no vaccine was $323 456 per QALY.

Results of Sensitivity Analysis: In deterministic and scenario sensitivity analyses, the only variables that produced an ICER less than $100 000 per QALY were vaccine cost (at a value of $80) and the rate at which efficacy wanes. In probabilistic sensitivity analysis, the mean ICER was $500 754 per QALY (95% CI, $93 510 to $1 691 211 per QALY). At a willingness-to-pay threshold of $100 000 per QALY, the probability that vaccination would be cost-effective was 3%.

Limitation: Long-term effectiveness data for HZ vaccine are lacking for 50-year-old adults.

Conclusion: Herpes zoster vaccine for persons aged 50 years does not seem to represent good value according to generally accepted standards. Our findings support the decision of the Advisory Committee on Immunization Practices not to recommend the vaccine for adults in this age group.

Primary Funding Source: None.

Figures

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Appendix Figure 1.

Markov model: decision node and Markov states.

The model begins with a decision node representing the choice between the vaccine or no vaccination. The cohort then moves to a chance node (open circle) of male or female, depending on the sex distribution of the general population, and then enters the Markov node (letter "M" inside circle). For the first cycle, the entire cohort enters the "healthy" state, then moves between Markov health states depending on transition probabilities in subsequent cycles until everyone is subsumed by the "dead" state, at which point the model terminates.

Grahic Jump Location
Grahic Jump Location
Appendix Figure 2.

Markov model: sub-tree.

The chance of events occurring within each annual cycle for persons starting at the "healthy" state. For subsequent cycles beginning in the "monocular blindness", "monaural deafness", or "monocular blindness and monaural deafness" states, the tree is identical, but cohort members return to the corresponding initial states instead of "healthy" after recovering from HZ and any short-term complications (hospitalization and PHN). Those who acquire a second disability move to the combined disability state. Bilateral blindness and deafness are extremely rare and are not considered. HZ = herpes zoster; PHN = postherpetic neuralgia.

Grahic Jump Location
Grahic Jump Location
Figure 1.

Reduction in vaccine efficacy, by number of years after vaccination.

The linear line was estimated using data from the Long-Term Persistence Substudy (6) for herpes zoster vaccine among persons aged ≥60 y.

Grahic Jump Location
Grahic Jump Location
Appendix Figure 3.

Costs versus QALYs for different vaccination ages.

Vaccination at age 59 y, which had the lowest costs and highest QALYs, dominated vaccination at all other ages. The slope of the line between the "no vaccine" and "vaccine at age 59 y" points represents the incremental cost per QALY saved ($113 121) when the 2 strategies were compared. QALY = quality-adjusted life-year.

Grahic Jump Location
Grahic Jump Location
Appendix Figure 4.

Costs versus QALYs for different booster strategies.

The "vaccine at age 50 y and booster at age 55 y" strategy was dominated because it had a higher cost and lower QALYs than the "vaccine at age 50 y and booster at age 60 y" strategy. The "vaccine at age 50 y and no booster" strategy was not considered for comparison due to extended dominance; it had a higher incremental cost per QALY (ICER) than the next more effective strategy, which was "vaccine at age 50 y and booster at age 60 y". The slope of the line between the "no vaccine" and "vaccine at age 50 y and booster at age 60 y" points represents the ICER of $174 926 per QALY when the 2 strategies were compared. ICER = incremental cost-effectiveness ratio; QALY = quality-adjusted life-year.

Grahic Jump Location
Grahic Jump Location
Figure 2.

Tornado diagram of the factors with the most influence on the ICER.

Ranges are in parentheses, with the left values leading to the leftmost ICERs. ICER = incremental cost-effectiveness ratio; PHN = postherpetic neuralgia; QALY = quality-adjusted life-year.* Ranges for these age-specific parameters are specified in Table 1, with the highest values leading to the leftmost ICERs.

Grahic Jump Location
Grahic Jump Location
Figure 3.

Incremental costs of the herpes zoster vaccine per QALY saved, as a function of vaccine cost and sex.

When cost was <$80 per dose, the incremental costs were <$100 000 per QALY for the whole population. Because women had higher herpes zoster incidence, the incremental costs were <$100 000 per QALY at a higher vaccine cost per dose ($105); the reverse was true for men. ICER = incremental cost-effectiveness ratio; QALY = quality-adjusted life-year.

Grahic Jump Location
Grahic Jump Location
Figure 4.

Cost-effectiveness acceptability curve for the herpes zoster vaccine versus no vaccination at age 50 y.

QALY = quality-adjusted life-year.

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Comments

Submit a Comment/Letter
Zoster Vaccination Age 50-59
Posted on November 5, 2015
Vivek Kumar, B.S., Jason Kessler, M.D., MPH, Elisabeth J. Cohen, M.D.
NYU School Of Medicine, NYU Langone Medical Center, Department of Population Health, Department of Medicine, Department of Ophthalmology
Conflict of Interest: None Declared
To the editor,

In a recent issue of the Annals of Internal Medicine, Drs. Le and Rothberg wrote an analysis which supports the recommendation by the Centers for Disease Control (CDC) for herpes zoster (HZ) vaccine for immunocompetent people aged 60 years or older, despite Food and Drug Administration (FDA) approval for adults aged 50 years or older since 2011. We would like to counter these arguments and explain why doctors should recommend this vaccine to eligible people age 50 years and older.

A key assumption of the article was that the incidence of HZ would plateau after 2010 or 2015. This assumption seems unlikely to be true however, as there is evidence that HZ incidence continues to increase and is modeled to increase for 50 years.(1) Increasing HZ incidence is associated with increased efficiency of earlier vaccination.

Another assumption of the article was that vaccine efficacy waned at the same rate regardless of age. A recent study shows that the reduction in vaccine efficacy is closely associated with age at vaccination in patients age 60 and older (i.e. protection of HZ vaccination lasts longer in younger patients).(2) According to the sensitivity analysis presented in this paper, if vaccination efficacy decreases at half the rate in people age 50-59, then the vaccine is cost-effective (ICER $48,457/QALY).

Finally, the productivity loss associated with HZ was estimated from a retrospective phone survey with a low response rate. A prospective study found productivity losses in younger patients (i.e. 50-59) to be greater than losses in older patients (i.e.≥60 y/o).(3) Inclusion of a sensitivity analysis taking into account increased loss of productivity age 50-59, would also support vaccination in this younger cohort.

Other studies have found that vaccinating at age 50 is cost effective.(4) We believe that further study is required to determine the true ICER of Herpes Zoster Vaccine administration in patients aged 50. In the meantime, since the greatest number cases of zoster occur in people in their 50s when the vaccine is most effective in preventing disease, non-pain complications do not increase with age, the vaccine duration of efficacy is likely to be longer, and loss of productivity greater in this age group, we strongly recommend that immunocompetent persons in their 50s receive the zoster vaccine.(5)

1. MacIntyre, R., et al., Increasing trends of herpes zoster in Australia. PLoS One, 2015. 10(4): p. e0125025.
2. Li, X., et al., Modeling the durability of ZOSTAVAX(R) vaccine efficacy in people >/=60 years of age. Vaccine, 2015. 33(12): p. 1499-505.
3. Drolet, M., et al., A prospective study of the herpes zoster severity of illness. Clin J Pain, 2010. 26(8): p. 656-66.
4. Preaud, E., et al., Cost-effectiveness analysis of a vaccination program for the prevention of herpes zoster and post-herpetic neuralgia in adults aged 50 and over in Germany. Hum Vaccin Immunother, 2015. 11(4): p. 884-96.
5. Yawn, B.P., et al., A population-based study of the incidence and complication rates of herpes zoster before zoster vaccine introduction. Mayo Clin Proc, 2007. 82(11): p. 1341-9.
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