University of Groningen
An economic assessment of high-dose influenza vaccine
van Aalst, Robertus
DOI:
10.33612/diss.127973664
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Publication date: 2020
Link to publication in University of Groningen/UMCG research database
Citation for published version (APA):
van Aalst, R. (2020). An economic assessment of high-dose influenza vaccine: Estimating the vaccine-preventable burden of disease in the United States using real-world data. University of Groningen. https://doi.org/10.33612/diss.127973664
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SUMMARY
Adults 65 years and older (hereinafter referred to as seniors) are at greater risk for complications following influenza infection compared with younger adults, due to decreased vaccine efficacy and increased prevalence of chronic medical conditions with increasing age. Currently in the U.S., two influenza vaccines are licensed exclusively for use in seniors: a high-dose influenza vaccine (HD-IIV3) and an adjuvanted influenza vaccine (aIIV3). HD-IIV3 aims to improve protection through quadrupling the antigen dose per influenza strain, whereas aIIV3 is a standard-dose vaccine (SD-IIV3) to which an oil-in-water emulsion of squalene oil is added. HD-IIV3 is often offered at a price premium compared to SD-IIV3 and aIIV3. In this thesis we attempted to answer if this premium is worthwhile. We studied two specific sub-populations in the United States – Veterans receiving care through the Veterans Health Administration (VHA) and members of a large national managed care company affiliated with Optum. For our analyses we used real-word data (RWD): health insurance claims data and electronic medical records from VHA, Medicare and Optum. The availability of large databases with data of millions of people makes affordable retrospective cohort studies possible but introduces unique challenges when trying to find causal relationships. We discuss the causal interpretation of rate-change methods and propose a novel approach to test its sensitivity to violations of underlying assumptions. We conclude that HD-IIV3 is associated with less hospitalizations compared to SD-IIV3 and aIIV3. The avoided hospitalization costs offset HD-IIV3’s higher price and resulted in net cost savings.
SAMENVATTING
Volwassenen van 65 jaar en ouder (hierna senioren genoemd) lopen een groter risico op complicaties na een griepinfectie in vergelijking met jongere volwassenen. Dit wordt gedeeltelijk veroorzaakt door een verlaagde werkzaamheid van het griepvaccin en een verhoogde prevalentie van chronische aandoeningen op oudere leeftijd. Momenteel zijn in de Verenigde Staten twee griepvaccins exclusief in licentie gegeven voor gebruik bij senioren: een hoge-dosis griepvaccin (HD-IIV3) en een adjuvanted griepvaccin (aIIV3). HD-IIV3 heeft tot doel de bescherming te verbeteren door de antigeendosis per griepstam te verviervoudigen, terwijl aIIV3 een standaard-dosis vaccin (SD-IIV3) is waaraan een olie-in-water-emulsie van squaleenolie is toegevoegd. HD-IIV3 wordt vaak aangeboden tegen een hogere prijs in vergelijking met SD-IIV3 en aIIV3. In dit proefschrift hebben we geprobeerd te beantwoorden of deze premie de moeite waard is. We hebben twee specifieke subpopulaties in de VS bestudeerd: veteranen die zorg krijgen via de Veterans Health Administration (VHA) en verzekeringsnemers van een nationale “managed care” aanbieder geaffilieerd met Optum. Voor onze analyses hebben we gebruik gemaakt van real-word data (RWD): ziektekostenverzekering claimgegevens en elektronische medische dossiers van VHA en Optum. De beschikbaarheid van grote databases met gegevens van miljoenen mensen maakt betaalbare retrospectieve cohortstudies mogelijk, maar brengt unieke uitdagingen met zich mee bij het zoeken naar causale relaties. We bespreken de causale interpretatie van “rate-change” methodes en stellen een nieuwe benadering voor om de gevoeligheid ervan voor schendingen van onderliggende veronderstellingen te testen. We concluderen dat HD-IIV3 geassocieerd is met minder ziekenhuisopnames vergeleken met SD-IIV3 en aIIV3. De vermeden ziekenhuiskosten compenseerden de hogere prijs van HD-IIV3 en resulteerden in netto kostenbesparingen.
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ACKNOWLEDGMENTS
I could not have written my thesis without the help of some of the smartest and funniest people I ever had the pleasure of working with. First of all, Prof. Dr. Ayman Chit, who introduced me to my promotors Prof. Dr. Maarten Postma and Prof. Dr. Jan Wilschut. Ayman, thank you for calling this play and allowing me to score a touchdown. Maarten, thank you for taking me on as a “buitenpromovendus”, always being in the same time-zone (unless you don’t sleep) and for your endless energy and positive attitude. Jan, your observations through a non-economic lens were quite insightful. A big thank you as well to the other members of the advisory committee: Prof. Dr. Yinong Young-Xu, Prof. Dr. Salah Mahmud and Prof. Dr. Vincent Mor. Yinong, thank you for introducing me to the field of epidemiology and teaching me the difference between incidence and prevalence (I had to start somewhere, might as well be at the beginning). Thanks to you I found a second career that I truly love. Salah, I must thank you for your efforts to improve my writing skills. It will always be work in progress. And Vince, thanks for your suggestion that I would enjoy the causal inference classes at Brown from Prof. Dr. Issa Dahabreh. Not only did I enjoy them, I learned that I needed them (which was probably your point to begin with). Issa, I will never forget working with you on the PERR paper – a learning experience in multiple dimensions. I would like to thank Prof. Dr. Stefan Gravenstein for clinical insights and interpretation of results, and Ellyn Russo and Nabin Neupane for project coordination and data-analysis of VA data. In addition, I would like to thank all my co-authors for all their comments and suggestions to improve the manuscripts.
PUBLICATION LIST
1. Van Aalst R, Thommes EW, Postma M, Chit A, Dahabreh IJ. On the causal interpretation of rate-change methods: the prior event rate ratio and rate difference (in press). American Journal of Epidemiolog y. 2020.
2. Moyo P, Zullo AR, McConeghy KW, Bosco E, van Aalst R, Chit A, Gravenstein S. Risk factors for pneumonia and influenza hospitalizations in long-term care facility residents: a retrospective cohort study. BMC geriatrics. 2020;20(1):47.
3. Kalligeros M, Shehadeh F, Mylona EK, Dapaah-Afriyie C, van Aalst R, Chit A, Mylonakis E. Influenza vaccine effectiveness against influenza-associated hospitalization in children: A systematic review and meta-analysis. Vaccine. 2020.
4. Bosco E, Zullo AR, McConeghy KW, Moyo P, van Aalst R, Chit A, Mwenda KM, Panozzo CA, Mor V, Gravenstein S. Geographic Variation in Pneumonia and Influenza in Long-Term Care Facilities: A National Study. Clinical Infectious Diseases.
2020.
5. Loiacono MM, Mahmud SM, Chit A, van Aalst R, Kwong JC, Mitsakakis N, Skinner L, Thommes E, Bricout H, Grootendorst P. Patient and practice level factors associated with seasonal influenza vaccine uptake among at-risk adults in England, 2011 to 2016: an age-stratified retrospective cohort study. Vaccine: X.
2020:100054.
6. Van Aalst R, Gravenstein S, Mor V, Mahmud SM, Wilschut J, Postma M, Chit A. Comparative effectiveness of high dose versus adjuvanted influenza vaccine: A retrospective cohort study. Vaccine. 2020;38(2):372-9.
7. Young-Xu Y, Snider JT, van Aalst R, Mahmud SM, Thommes EW, Lee JKH, Greenberg DP, Chit A. Analysis of relative effectiveness of high-dose versus standard-dose influenza vaccines using an instrumental variable method. Vaccine.
268
8. Van Aalst R, Russo EM, Neupane N, Mahmud SM, Mor V, Wilschut J, Chit A, Postma M, Young-Xu Y. Economic assessment of a high-dose versus a standard-dose influenza vaccine in the US Veteran population: Estimating the impact on hospitalization cost for cardio-respiratory disease. Vaccine. 2019;37(32):4499-503.
9. Thommes EW, Mahmud SM, Young-Xu Y, Snider JT, van Aalst R, Lee JKH, Halchenko Y, Russo E, Chit A. Assessing the prior event rate ratio method via probabilistic bias analysis on a Bayesian network. Stat Med. 2019.
10. Poudel S, Shehadeh F, Zacharioudakis IM, Tansarli GS, Zervou FN, Kalligeros M, van Aalst R, Chit A, Mylonakis E. The Effect of Influenza Vaccination on Mortality and Risk of Hospitalization in Patients With Heart Failure: A Systematic Review and Meta-analysis. Open Forum Infect Dis. 2019;6(4):ofz159.
11. Cohen E, Bradley J, van Aalst R, Ogrinc G. Evolution of a Resident Quality Improvement Curriculum: Lessons Learned on the Path from Innovation Through Stability to Contraction. Jt Comm J Qual Patient Saf. 2019;45(8):575-9.
12. Childs A, Zullo AR, Joyce NR, McConeghy KW, van Aalst R, Moyo P, Bosco E, Mor V, Gravenstein S. The burden of respiratory infections among older adults in long-term care: a systematic review. BMC geriatrics. 2019;19(1):210.
13. Bosco E, Zullo AR, McConeghy KW, Moyo P, van Aalst R, Chit A, Mor V, Gravenstein S. Long-term Care Facility Variation in the Incidence of Pneumonia and Influenza. Open Forum Infect Dis. 2019;6(6):ofz230.
14. Young-Xu Y, Van Aalst R, Mahmud SM, Rothman KJ, Snider JT, Westreich D, Mor V, Gravenstein S, Lee JKH, Thommes EW, et al. Relative Vaccine Effectiveness of High-Dose Versus Standard-Dose Influenza Vaccines Among Veterans Health Administration Patients. J Infect Dis. 2018;217(11):1718-27.
15. King B, Young-Xu Y, Lee WJ, van Aalst R, Shiner B, Mills P, Eickhoff L, Neily J. Impact of The Daily Plan on Length of Stay and Readmission. J Nurs Care Qual.
16. Jolin J, van Aalst R, Volpp B, Taylor T, Cohen E. Using an Inpatient Quality Improvement Curriculum for Internal Medicine Residents to Improve Pneumococcal Conjugate Vaccine Administration Rates. Jt Comm J Qual Patient Saf. 2018;44(6):328-33.
17. Young-Xu Y, van Aalst R, Russo E, Lee JK, Chit A. The Annual Burden of Seasonal Influenza in the US Veterans Affairs Population. PLoS One. 2017;12(1):e0169344.
18. Ogrinc G, Cohen ES, van Aalst R, Harwood B, Ercolano E, Baum KD, Pattison AJ, Jones AC, Davies L, West A. Clinical and Educational Outcomes of an Integrated Inpatient Quality Improvement Curriculum for Internal Medicine Residents. J Grad Med Educ. 2016;8(4):563-8.
19. Ogrinc G, Ercolano E, Cohen ES, Harwood B, Baum K, van Aalst R, Jones AC, Davies L. Educational system factors that engage resident physicians in an integrated quality improvement curriculum at a VA hospital: a realist evaluation.
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RESEARCH INSTITUTE SHARE
This thesis is published within the Research Institute SHARE (Science in Healthy Ageing and healthcaRE) of the University Medical Center Groningen / University of Groningen.
Further information regarding the institute and its research can be obtained from our internet site: http://www.share.umcg.nl/
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CURRICULUM VITAE
Robertus van Aalst was born in Doetinchem, the Netherlands on 22 January 1970. After finishing high school at Liemers College in Zevenaar, he started to study Industrial Engineering and Management Science at the University of Technology in Eindhoven and obtained his master degree in Operations Research and Statistics in 1994. After his graduation, Rob worked for a variety of Dutch companies, mostly in the field of quality assurance and improvement. In 2005 he followed his American wife to Dartmouth-Hitchcock Medical Center in Lebanon, NH, USA, where she started an Internal Medicine residency and he became the primary caregiver for their one-year-old daughter. In 2011, Rob joined the Veterans Affairs (VA) Medical Center in White River Junction, VT, as its Industrial Engineer, leading providers and administrators in quality improvement initiatives based on his analyses of provider productivity and hospital (human) resources. In 2015, Rob left hospital administration and joined the VA Clinical Epidemiology Program at White River Junction as a data-analyst. Under the mentorship of Dr. Young-Xu he became a research associate within a year. Rob left the Clinical Epidemiology Program to work for Sanofi Pasteur in 2017 but continues to work closely with Dr. Young-Xu and his team. At Sanofi, Rob started to work on his PhD early-on while leading prospective and retrospective studies to estimate the burden of disease of influenza and respiratory syncytial virus (RSV) and better understand the effectiveness of influenza vaccines. He is currently heavily involved in Sanofi Pasteur’s COVID-19 research agenda.
