
When vaccinating against influenza, some countries focus on elderly persons because observational studies indicate that this practice decreases both population mortality and the frequency of hospitalization. This new study finds different results with a different research design that reduces the bias and confounding that might have affected other studies.
Background:
Observational studies using traditional research designs suggest that influenza vaccination reduces hospitalizations and mortality among elderly persons. Accordingly, health authorities in some countries prioritize vaccination of this population. Nevertheless, questions remain about this policy's effectiveness given the potential for bias and confounding in observational data.
Objective:
To determine the effectiveness of the influenza vaccine in reducing hospitalizations and mortality among elderly persons by using an observational research design that reduces the possibility of bias and confounding.
Design:
A regression discontinuity design was applied to the sharp change in vaccination rate at age 65 years that resulted from an age-based vaccination policy in the United Kingdom. In this design, comparisons were limited to individuals who were near the age-65 threshold and were thus plausibly similar along most dimensions except vaccination rate.
Setting:
England and Wales.
Participants:
Adults aged 55 to 75 years residing in the study area during 2000 to 2014.
Intervention:
Seasonal influenza vaccine.
Measurements:
Hospitalization and mortality rates by month of age.
Results:
The data included 170 million episodes of care and 7.6 million deaths. Turning 65 was associated with a statistically and clinically significant increase in rate of seasonal influenza vaccination. However, no evidence indicated that vaccination reduced hospitalizations or mortality among elderly persons. The estimates were precise enough to rule out results from many previous studies.
Limitation:
The study relied on observational data, and its focus was limited to individuals near age 65 years.
Conclusion:
Current vaccination strategies prioritizing elderly persons may be less effective than believed at reducing serious morbidity and mortality in this population, which suggests that supplementary strategies may be necessary.
Primary Funding Source:
National Institute on Aging.
References
- 1.
Peasah SK ,Azziz-Baumgartner E ,Breese J ,et al . Influenza cost and cost-effectiveness studies globally—a review. Vaccine. 2013;31:5339-48. [PMID: 24055351] doi:10.1016/j.vaccine.2013.09.013 CrossrefMedlineGoogle Scholar - 2.
Longini IM Jr andHalloran ME . Strategy for distribution of influenza vaccine to high-risk groups and children. Am J Epidemiol. 2005;161:303-6. [PMID: 15692073] CrossrefMedlineGoogle Scholar - 3.
Basta NE ,Chao DL ,Halloran ME ,et al . Strategies for pandemic and seasonal influenza vaccination of schoolchildren in the United States. Am J Epidemiol. 2009;170:679-86. [PMID: 19679750] doi:10.1093/aje/kwp237 CrossrefMedlineGoogle Scholar - 4.
Medlock J andGalvani AP . Optimizing influenza vaccine distribution. Science. 2009;325:1705-8. [PMID: 19696313] doi:10.1126/science.1175570 CrossrefMedlineGoogle Scholar - 5.
Monto AS ,Davenport FM ,Napier JA ,et al . Modification of an outbreak of influenza in Tecumseh, Michigan by vaccination of schoolchildren. J Infect Dis. 1970;122:16-25. [PMID: 5433709] CrossrefMedlineGoogle Scholar - 6.
Rudenko LG ,Slepushkin AN ,Monto AS ,et al . Efficacy of live attenuated and inactivated influenza vaccines in schoolchildren and their unvaccinated contacts in Novgorod, Russia. J Infect Dis. 1993;168:881-7. [PMID: 8376833] CrossrefMedlineGoogle Scholar - 7.
Hurwitz ES ,Haber M ,Chang A ,et al . Effectiveness of influenza vaccination of day care children in reducing influenza-related morbidity among household contacts. JAMA. 2000;284:1677-82. [PMID: 11015798] CrossrefMedlineGoogle Scholar - 8.
Ghendon YZ ,Kaira AN , andElshina GA . The effect of mass influenza immunization in children on the morbidity of the unvaccinated elderly. Epidemiol Infect. 2006;134:71-8. [PMID: 16316494] CrossrefMedlineGoogle Scholar - 9.
Glezen WP . Herd protection against influenza. J Clin Virol. 2006;37:237-43. [PMID: 17008123] CrossrefMedlineGoogle Scholar - 10.
King JC Jr ,Stoddard JJ ,Gaglani MJ ,et al . Effectiveness of school-based influenza vaccination. N Engl J Med. 2006;355:2523-32. [PMID: 17167135] CrossrefMedlineGoogle Scholar - 11.
Loeb M ,Russell ML ,Moss L ,et al . Effect of influenza vaccination of children on infection rates in Hutterite communities: a randomized trial. JAMA. 2010;303:943-50. [PMID: 20215608] doi:10.1001/jama.2010.250 CrossrefMedlineGoogle Scholar - 12.
Govaert TM ,Thijs CT ,Masurel N ,et al . The efficacy of influenza vaccination in elderly individuals. A randomized double-blind placebo-controlled trial. JAMA. 1994;272:1661-5. [PMID: 7966893] CrossrefMedlineGoogle Scholar - 13.
Allsup S ,Haycox A ,Regan M ,et al . Is influenza vaccination cost effective for healthy people between ages 65 and 74 years? A randomised controlled trial. Vaccine. 2004;23:639-45. [PMID: 15542184] MedlineGoogle Scholar - 14.
Gross PA ,Hermogenes AW ,Sacks HS ,et al . The efficacy of influenza vaccine in elderly persons. A meta-analysis and review of the literature. Ann Intern Med. 1995;123:518-27 LinkGoogle Scholar - 15.
Jefferson T ,Rivetti D ,Rivetti A ,et al . Efficacy and effectiveness of influenza vaccines in elderly people: a systematic review. Lancet. 2005;366:1165-74. [PMID: 16198765] CrossrefMedlineGoogle Scholar - 16.
Nichol KL ,Nordin JD ,Nelson DB ,et al . Effectiveness of influenza vaccine in the community-dwelling elderly. N Engl J Med. 2007;357:1373-81. [PMID: 17914038] CrossrefMedlineGoogle Scholar - 17.
Mangtani P ,Cumberland P ,Hodgson CR ,et al . A cohort study of the effectiveness of influenza vaccine in older people, performed using the United Kingdom General Practice Research Database. J Infect Dis. 2004;190:1-10. [PMID: 15195237] CrossrefMedlineGoogle Scholar - 18.
Fireman B ,Lee J ,Lewis N ,et al . Influenza vaccination and mortality: differentiating vaccine effects from bias. Am J Epidemiol. 2009;170:650-6. [PMID: 19625341] doi:10.1093/aje/kwp173 CrossrefMedlineGoogle Scholar - 19.
Baxter R ,Ray GT , andFireman BH . Effect of influenza vaccination on hospitalizations in persons aged 50 years and older. Vaccine. 2010;28:7267-72. [PMID: 20832494] doi:10.1016/j.vaccine.2010.08.088 CrossrefMedlineGoogle Scholar - 20.
Correa A ,Hinton W ,McGovern A ,et al . Royal College of General Practitioners Research and Surveillance Centre (RCGP RSC) sentinel network: a cohort profile. BMJ Open. 2016;6:e011092. [PMID: 27098827] doi:10.1136/bmjopen-2016-011092 CrossrefMedlineGoogle Scholar - 21.
Bor J ,Moscoe E ,Mutevedzi P ,et al . Regression discontinuity designs in epidemiology: causal inference without randomized trials. Epidemiology. 2014;25:729-37. [PMID: 25061922] doi:10.1097/EDE.0000000000000138 CrossrefMedlineGoogle Scholar - 22.
O'Keeffe AG ,Geneletti S ,Baio G ,et al . Regression discontinuity designs: an approach to the evaluation of treatment efficacy in primary care using observational data. BMJ. 2014;349:g5293. [PMID: 25199521] doi:10.1136/bmj.g5293 CrossrefMedlineGoogle Scholar - 23.
Venkataramani AS ,Bor J , andJena AB . Regression discontinuity designs in healthcare research. BMJ. 2016;352:i1216. [PMID: 26977086] doi:10.1136/bmj.i1216 CrossrefMedlineGoogle Scholar - 24.
Sood N ,Bendavid E ,Mukherji A ,et al . Government health insurance for people below poverty line in India: quasi-experimental evaluation of insurance and health outcomes. BMJ. 2014;349:g5114. [PMID: 25214509] doi:10.1136/bmj.g5114 CrossrefMedlineGoogle Scholar - 25.
Stevenson AJ ,Flores-Vazquez IM ,Allgeyer RL ,et al . Effect of removal of Planned Parenthood from the Texas Women's Health Program. N Engl J Med. 2016;374:853-60. [PMID: 26836435] doi:10.1056/NEJMsa1511902 CrossrefMedlineGoogle Scholar - 26.
Chen H ,Li Q ,Kaufman JS ,et al . Effect of air quality alerts on human health: a regression discontinuity analysis in Toronto, Canada. Lancet Planet Health. 2018;2:e19-26. [PMID: 29615204] doi:10.1016/S2542-5196(17)30185-7 CrossrefMedlineGoogle Scholar - 27.
Melamed A ,Fink G ,Wright AA ,et al . Effect of adoption of neoadjuvant chemotherapy for advanced ovarian cancer on all cause mortality: quasi-experimental study. BMJ. 2018;360:j5463. [PMID: 29298771] doi:10.1136/bmj.j5463 CrossrefMedlineGoogle Scholar - 28.
Imbens GW andLemieux T . Regression discontinuity designs: a guide to practice. J Econom. 2008;142:615-35. doi:10.1016/j.jeconom.2007.05.001 CrossrefGoogle Scholar - 29.
Dimick JB andRyan AM . Methods for evaluating changes in health care policy: the difference-in-differences approach. JAMA. 2014;312:2401-2. [PMID: 25490331] doi:10.1001/jama.2014.16153 CrossrefMedlineGoogle Scholar - 30.
Ahmed AE ,Nicholson KG , andNguyen-Van-Tam JS . Reduction in mortality associated with influenza vaccine during 1989-90 epidemic. Lancet. 1995;346:591-5. [PMID: 7651002] CrossrefMedlineGoogle Scholar - 31.
Fleming DM ,Watson JM ,Nicholas S ,et al . Study of the effectiveness of influenza vaccination in the elderly in the epidemic of 1989-90 using a general practice database. Epidemiol Infect. 1995;115:581-9. [PMID: 8557090] CrossrefMedlineGoogle Scholar - 32.
Ahmed AH ,Nicholson KG ,Nguyen-van Tam JS ,et al . Effectiveness of influenza vaccine in reducing hospital admissions during the 1989-90 epidemic. Epidemiol Infect. 1997;118:27-33. [PMID: 9042032] CrossrefMedlineGoogle Scholar - 33.
Miller RA . Aging and immune function. Int Rev Cytol. 1991;124:187-215. [PMID: 2001916] CrossrefMedlineGoogle Scholar - 34.
Miller RA . The aging immune system: primer and prospectus. Science. 1996;273:70-4. [PMID: 8658199] CrossrefMedlineGoogle Scholar - 35.
Yung RL . Changes in immune function with age. Rheum Dis Clin North Am. 2000;26:455-73. [PMID: 10989507] CrossrefMedlineGoogle Scholar - 36.
Kumar SS ,Ventura AK , andVanderWerf B . Influenza vaccination in renal transplant recipients. JAMA. 1978;239:840-2. [PMID: 342736] CrossrefMedlineGoogle Scholar - 37.
Gross PA ,Lee H ,Wolff JA ,et al . Influenza immunization in immunosuppressed children. J Pediatr. 1978;92:30-5. [PMID: 619076] CrossrefMedlineGoogle Scholar - 38.
Kiecolt-Glaser JK ,Glaser R ,Gravenstein S ,et al . Chronic stress alters the immune response to influenza virus vaccine in older adults. Proc Natl Acad Sci U S A. 1996;93:3043-7. [PMID: 8610165] CrossrefMedlineGoogle Scholar - 39.
Tasker SA ,Treanor JJ ,Paxton WB ,et al . Efficacy of influenza vaccination in HIV-infected persons. A randomized, double-blind, placebo-controlled trial. Ann Intern Med. 1999;131:430-3 LinkGoogle Scholar - 40.
Shrestha S ,Foxman B ,Weinberger DM ,et al . Identifying the interaction between influenza and pneumococcal pneumonia using incidence data. Sci Transl Med. 2013;5:191ra84. [PMID: 23803706] doi:10.1126/scitranslmed.3005982 CrossrefMedlineGoogle Scholar - 41.
Ward CJ . Influenza vaccination campaigns: is an ounce of prevention worth a pound of cure? Am Econ J Appl Econ. 2014;6:38-72. doi:10.1257/app.6.1.38 CrossrefGoogle Scholar - 42. U.S. Census Bureau. Methodology for the intercensal population and housing unit estimates: 2000 to 2010. October 2012. Accessed at www2.census.gov/programs-surveys/popest/technical-documentation/methodology/intercensal/2000-2010-intercensal-estimates-methodology.pdf on 14 December 2016. Google Scholar
Author, Article and Disclosure Information
Disclaimer: The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or the U.S. Department of Agriculture.
Acknowledgment: The authors thank seminar participants at ASHEcon; Brigham Young University; Clemson University; University of California, Irvine; University of Connecticut; University of Illinois at Urbana-Champaign; and University of South Carolina.
Grant Support: By award R01AG044796 from the National Institute on Aging of the National Institutes of Health and by Hatch project 233535 from the National Institute of Food and Agriculture of the U.S. Department of Agriculture. Eighty percent of the project was funded by federal sources, and none was funded by nongovernmental sources.
Disclosures: Drs. Anderson, Dobkin, and Gorry report grants from the National Institute on Aging of the National Institutes of Health during the conduct of the study. Disclosures can also be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M19-3075.
Editors' Disclosures: Christine Laine, MD, MPH, Editor in Chief, reports that her spouse has stock options/holdings with Targeted Diagnostics and Therapeutics. Darren B. Taichman, MD, PhD, Executive 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. Jaya K. Rao, MD, MHS, Deputy Editor, reports that she has stock holdings/options in Eli Lilly and Pfizer. Christina C. Wee, MD, MPH, Deputy Editor, reports employment with Beth Israel Deaconess Medical Center. Sankey V. Williams, MD, Deputy Editor, reports that he has no financial relationships or interests to disclose. Yu-Xiao Yang, MD, MSCE, Deputy Editor, reports that he has no financial relationships or interest to disclose.
Reproducible Research Statement: Study protocol: Not available. Statistical code: Available at https://doi.org/10.6078/D1Q11H. Data set: Available for purchase from the Royal College of General Practitioners Research and Surveillance Centre, the U.K. Office for National Statistics, the U.K. National Health Service Hospital Episode Statistics, the U.K. Data Archive, and Picker Institute Europe. The code archive provides details.
Corresponding Author: Michael L. Anderson, PhD, 714 University Hall, MC3310, University of California, Berkeley, Berkeley, CA 94720; e-mail, [email protected].
Current Author Addresses: Dr. Anderson: 714 University Hall, MC3310, University of California, Berkeley, Berkeley, CA 94720.
Dr. Dobkin: 441 Engineering 2, University of California, Santa Cruz, 1156 High Street, Santa Cruz, CA 95064.
Dr. Gorry: John E. Walker Department of Economics, 228 Sirrine Hall, Clemson, SC 29634.
Author Contributions: Conception and design: M.L. Anderson, C. Dobkin, D. Gorry.
Analysis and interpretation of the data: M.L. Anderson, C. Dobkin, D. Gorry.
Drafting of the article: M.L. Anderson, C. Dobkin, D. Gorry.
Critical revision of the article for important intellectual content: M.L. Anderson, C. Dobkin, D. Gorry.
Final approval of the article: M.L. Anderson, C. Dobkin, D. Gorry.
Provision of study materials or patients: C. Dobkin.
Statistical expertise: M.L. Anderson, C. Dobkin, D. Gorry.
Obtaining of funding: M.L. Anderson, C. Dobkin, D. Gorry.
Administrative, technical, or logistic support: C. Dobkin.
Collection and assembly of data: C. Dobkin, D. Gorry.
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