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Original Research |

Health and Economic Benefits of Early Vaccination and Nonpharmaceutical Interventions for a Human Influenza A (H7N9) Pandemic: A Modeling StudyBenefits of Early Vaccination for an Influenza A (H7N9) Pandemic

Nayer Khazeni, MD, MS; David W. Hutton, MS, PhD; Cassandra I.F. Collins, MPH; Alan M. Garber, MD, PhD; and Douglas K. Owens, MD, MS
[+] Article and Author Information

From Stanford University Medical Center and Center for Health Policy/Center for Primary Care and Outcomes Research, Stanford, California; University of Michigan, Ann Arbor, Michigan; Harvard University, Cambridge, Massachusetts; and Veterans Affairs Palo Alto Health Care System, Palo Alto, California.

Disclaimer: The content is solely the responsibility of the authors and does not necessarily represent the official views of the Agency for Healthcare Research and Quality.

Acknowledgment: The authors thank Charlotte Chae for her assistance with the graphics.

Grant Support: In part by Agency for Healthcare Research and Quality (grant 5 K08 HS 019816; Dr. Khazeni), National Institutes of Health (grant 5 R01 DA015612-12; Dr. Owens), and Veterans Affairs Palo Alto Health Care System (Dr. Owens).

Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M13-2071.

Reproducible Research Statement: Study protocol, statistical code, and data set: An annotated version of the model is available in Supplement 1.

Requests for Single Reprints: Nayer Khazeni, MD, MS, Division of Pulmonary and Critical Care Medicine, Stanford University Medical Center, 300 Pasteur Drive, Room H3143, Stanford, CA 94305; e-mail, nayer@stanford.edu.

Current Author Addresses: Dr. Khazeni: Division of Pulmonary and Critical Care Medicine, Stanford University Medical Center, 300 Pasteur Drive, Room H3143, Stanford, CA 94305.

Drs. Hutton and Collins: Department of Health Management & Policy, 1415 Washington Heights, University of Michigan, Ann Arbor, MI 48109.

Dr. Garber: Office of the Provost, Harvard University, Cambridge, MA 02138.

Dr. Owens: Center for Health Policy/Center for Primary Care and Outcomes Research, 117 Encina Commons, Stanford University, Stanford, CA 94305.

Author Contributions: Conception and design: N. Khazeni, D.W. Hutton, D.K. Owens.

Analysis and interpretation of the data: N. Khazeni, D.W. Hutton, A.M. Garber, D.K. Owens.

Drafting of the article: N. Khazeni, D.W. Hutton, C.I.F. Collins.

Critical revision of the article for important intellectual content: N. Khazeni, D.W. Hutton.

Final approval of the article: N. Khazeni, D.W. Hutton, C.I.F. Collins, A.M. Garber, D.K. Owens.

Provision of study materials or patients: N. Khazeni.

Statistical expertise: N. Khazeni, D.W. Hutton, A.M. Garber, D.K. Owens.

Obtaining of funding: N. Khazeni, D.K. Owens.

Administrative, technical, or logistic support: N. Khazeni, A.M. Garber, C.I.F. Collins.

Collection and assembly of data: N. Khazeni, C.I.F. Collins.


Ann Intern Med. 2014;160(10):684-694. doi:10.7326/M13-2071
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Background: Vaccination for the 2009 pandemic did not occur until late in the outbreak, which limited its benefits. Influenza A (H7N9) is causing increasing morbidity and mortality in China, and researchers have modified the A (H5N1) virus to transmit via aerosol, which again heightens concerns about pandemic influenza preparedness.

Objective: To determine how quickly vaccination should be completed to reduce infections, deaths, and health care costs in a pandemic with characteristics similar to influenza A (H7N9) and A (H5N1).

Design: Dynamic transmission model to estimate health and economic consequences of a severe influenza pandemic in a large metropolitan city.

Data Sources: Literature and expert opinion.

Target Population: Residents of a U.S. metropolitan city with characteristics similar to New York City.

Time Horizon: Lifetime.

Perspective: Societal.

Intervention: Vaccination of 30% of the population at 4 or 6 months.

Outcome Measures: Infections and deaths averted and cost-effectiveness.

Results of Base-Case Analysis: In 12 months, 48 254 persons would die. Vaccinating at 9 months would avert 2365 of these deaths. Vaccinating at 6 months would save 5775 additional lives and $51 million at a city level. Accelerating delivery to 4 months would save an additional 5633 lives and $50 million.

Results of Sensitivity Analysis: If vaccination were delayed for 9 months, reducing contacts by 8% through nonpharmaceutical interventions would yield a similar reduction in infections and deaths as vaccination at 4 months.

Limitation: The model is not designed to evaluate programs targeting specific populations, such as children or persons with comorbid conditions.

Conclusion: Vaccination in an influenza A (H7N9) pandemic would need to be completed much faster than in 2009 to substantially reduce morbidity, mortality, and health care costs. Maximizing non-pharmaceutical interventions can substantially mitigate the pandemic until a matched vaccine becomes available.

Primary Funding Source: Agency for Healthcare Research and Quality, National Institutes of Health, and Department of Veterans Affairs.

Figures

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Appendix Figure 1.

SEIR model.

Dynamic infectious disease transmission model of progression of a severe pandemic with characteristics similar to influenza A (H7N9) and A (H5N1) in a susceptible population. We used a basic deterministic SEIR model with modifications to allow for various population groups (who receive pharmaceutical and nonpharmaceutical interventions). SEIR = susceptible, exposed, infected, and recovered.

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Figure 1.

Infections and deaths per day depending on timing of vaccination and mortality rate.

At high mortality rates, persons begin to reduce social interactions in response to the increased deaths—this reduces the number of infections per day but lengthens the epidemic. As this reactive social distancing decreases deaths, persons resume contacts, and that leads to sequential pandemic waves over time. The lines in this figure show deaths per day (areas under the curves represent cumulative deaths), which are generally higher for vaccination at 6 mo than 4 mo; however, with a mortality rate of 10%, after day 240, deaths per day for vaccination at 6 mo decrease below those per day for vaccination at 4 mo. By that time, more persons in the 6-mo vaccination category have been infected and developed immunity, which leads to fewer susceptible people and therefore fewer deaths. We see this only when we use the 10% mortality rate. When persons reduce social interactions because of a higher mortality rate, the epidemic lasts longer and influenza transmission is still sustained at day 240 and beyond. The total number of deaths for a 6-mo vaccination policy (represented by the total area under the curves) is always equal to or greater than that for a for 4-mo vaccination policy. The same reasoning explains why, later in the epidemic, daily death rates for vaccination at 9 mo decrease below those for 6 mo.

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Figure 2.

Infections and deaths per day with increasing NPIs.

If mass vaccination is delayed, public health officials could announce and implement the most restrictive NPIs (e.g., school closures or home quarantines) to mitigate the pandemic while vaccination is awaited. Increasing NPIs to 90% during pandemic days 30 to 60 would delay the first wave to 6 mo, and increasing to 90% during days 45 to 105 would delay the first wave to 9 mo. The lines in this figure show deaths per day (areas under the curves represent cumulative deaths). Deaths per day for vaccination at 6 mo are generally higher than those for vaccination at 4 mo; however, in the case of a 90% reduction in contacts because of NPIs, the daily deaths for vaccination at 6 mo decrease below those for vaccination at 4 mo later in the epidemic. By that time, more persons in the 6-mo vaccination category have been infected and developed immunity after infection, which leads to fewer susceptible people and therefore fewer deaths. The total number of deaths in a 6-mo vaccination policy (represented by the total area under the curves) is always equal to or greater than that in a 4-mo policy. The same reasoning explains why, later in the epidemic, daily death rates for vaccination at 9 mo decrease below those for 6 mo. NPI = nonpharmaceutical intervention.

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Appendix Figure 2.

Alternative vaccine distribution strategy (60-d rollout).

Rollout of vaccines by using new technologies may occur over an extended time frame. We examined distributing vaccines over 60 d by averaging the Centers for Disease Control and Prevention's estimates of vaccine delivery over 5 seasons. ICER = incremental cost-effectiveness ratio.

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Appendix Figure 3.

Cost-effectiveness acceptability curves for vaccine availability at 4 mo (top) and for vaccine availability at 4 mo with 60-d distribution, alternative levels of NPIs, and additional costs (bottom).

Additional investments would be necessary for a vaccine to be available at 4 mo. We conducted an analysis of several possible costs of a vaccine, per person vaccinated, assuming that 30% of the population is vaccinated. The cost-effectiveness acceptability curves show the likelihood that a vaccine at 4 mo would be cost-effective. Typically, cost-effectiveness acceptability curves show lines for each strategy. In this case, vaccination at 4 mo is compared with no vaccination and all other vaccination strategies (with no additional costs). The lines for the policies of “no vaccination,” “vaccination at 9 mo,” and “vaccination at 6 mo” are not shown for clarity. We also examined 60-d vaccine distribution schedules, alternative levels of NPIs, and additional costs for expediting vaccine delivery ranging from $10 to $1000. NPI = nonpharmaceutical intervention.

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Appendix Figure 4.

Additional costs of vaccination at 4 mo versus 6 mo for different mortality rates.

As the rate increases, additional lives can be saved through earlier vaccination. At a rate of 10%, an additional cost of $1000 to vaccinate each person at 4 vs. 6 mo would have an incremental cost of $24 000 per QALY gained. When this proportion is lower than 0.5%, however, fewer lives are saved through earlier vaccination, and even an additional cost of $125 per person would result in an incremental cost >$50 000 per QALY gained to vaccinate at 4 vs. 6 mo. ICER = incremental cost-effectiveness ratio; QALY = quality-adjusted life-year.

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