© 2009 American Public Health Association DOI: 10.2105/AJPH.2008.151332
Jennifer C. Nelson, Rachel C. L. Bittner, Lora Bounds, Shanshan Zhao, and Lisa A. Jackson are with the Group Health Research Institute, Seattle, WA. Jennifer C. Nelson, Rachel C. L. Bittner, and Shanshan Zhao are also with the Department of Biostatistics, University of Washington, Seattle. James Baggs is with the Centers for Disease Control and Prevention, Atlanta, GA. James G. Donahue is with the Epidemiology Research Center, Marshfield Clinic Research Foundation, Marshfield, WI. Simon J. Hambidge is with Kaiser Permanente Institute for Health Research, Denver Health Community Health Services, and University of Colorado, Denver, CO. Steven J. Jacobsen is with Research and Evaluation, Southern California Permanente Medical Group, Pasadena, CA. Nicola P. Klein is with the Vaccine Study Center and Division of Research, Northern California Kaiser Permanente, Oakland, CA. Allison L. Naleway is with Center for Health Research, Kaiser Permanente Northwest, Portland, OR. Kenneth M. Zangwill is with the Center for Vaccine Research at the University of California and the Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Los Angeles. Lisa A. Jackson is also with the Department of Epidemiology, University of Washington, Seattle. Correspondence: Correspondence should be sent to Jennifer C. Nelson, PhD, 1730 Minor Ave, Suite 1600, Seattle, WA 98101 (e-mail: nelson.jl{at}ghc.org). Reprints can be ordered at http://www.ajph.org by clicking on the "Reprints/Eprints" link.
Objectives. We studied compliance with multiple-dose vaccine schedules, assessed factors associated with noncompliance, and examined timeliness of series completion among older children, adolescents, and adults. Methods. We conducted a large, multisite, retrospective cohort study of older children, adolescents, and adults in the Vaccine Safety Datalink population from 1996 through 2004. We quantified the rates of completion of all required doses for varicella, hepatitis A, and hepatitis B vaccines according to their recommended schedules. Results. Among those who received a first dose of varicella (n = 16 075), hepatitis A (n = 594 917), and hepatitis B (n = 590 445) vaccine, relatively few completed the series (55%–65% for hepatitis B vaccine and 40%–50% for hepatitis A and varicella vaccines in most age groups). Compliance was lowest among adolescents (35.9%) and Medicaid recipients (29.7%) who received varicella vaccine and among younger adult age groups who received hepatitis A vaccine (25%–35% across those age groups). Even among series completers, there was a relatively long interval of undervaccination between the first and last doses. Conclusions. Compliance with multiple-dose vaccine series among older children, adolescents, and adults is suboptimal. Further evaluations of strategies to improve compliance in these populations are needed.
Many vaccines given to older children, adolescents, and adults require multiple doses for optimal immunogenicity and efficacy. Varicella vaccine is recommended in a 2-dose series for children 13 years or older without evidence of immunity.1 The hepatitis A2 and B3,4 vaccine series require 2 and 3 doses, respectively. Most recently, in 2007, vaccination with the 3-dose human papillomavirus vaccine series was recommended for adolescent and young adult women.5 Timely and complete vaccination with multiple-dose schedules is of public health importance, because an incomplete series may yield suboptimal disease protection.6–17 Comprehensive monitoring is conducted annually to evaluate compliance with vaccination schedules among infants and young children.18 However, there is little information on compliance with multiple-dose vaccine series in general populations of older children, adolescents, and adults.19–21 We conducted a large, population-based, retrospective cohort study of older children, adolescents, and adults in the Vaccine Safety Datalink population of approximately 8.8 million Medical Care Organization (MCO) enrollees, which represents about 3% of the US population. During the study period (1996–2004), we determined compliance with the 2- or 3-dose varicella, hepatitis A, or hepatitis B vaccine series in this population. We also assessed factors associated with noncompliance, and among those who completed the vaccination series, we examined the timeliness of completion to determine the excess duration of time that individuals remained undervaccinated.
The study population was composed of enrollees of 7 of the 8 MCOs participating in the Vaccine Safety Datalink project: Group Health (Washington), Kaiser Permanente Northwest (Oregon), Kaiser Permanente Medical Care Program of Northern California, Southern California Kaiser Permanente Health Care Program, HealthPartners Research Foundation (Minnesota), Marshfield Clinic (Wisconsin), and Kaiser Permanente Colorado. Each MCO has administrative data systems that record information on demographics, enrollment, immunizations, and International Classification of Disease, Ninth Revision, Clinical Modification (ICD-9-CM)22 codes assigned to medical encounters.23 The study period for each MCO was based on the availability of data from the MCO's immunization registry. Most sites contributed data from January 1, 1997 to December 31, 2004. One site's immunization registry extended back to 1996, and a second site began contributing data in 2000. Four sites did not contribute data on adults 18 years and older. Three cohorts of older children, adolescents, and adults were drawn from this population: (1) those who received a first dose of varicella vaccine on or after their 13th birthday, prior to their 46th birthday, and during the study period; (2) those who received a first dose of hepatitis A vaccine on or after their second birthday and during the study period; and (3) those who received a first dose of hepatitis B vaccine on or after their fifth birthday and during the study period. We chose lower age cutoffs for hepatitis A and B vaccines to exclude vaccines potentially received as part of the infant series and for varicella vaccine to include the population for which a 2-dose series has been recommended since vaccine licensure in 1996. To ensure complete identification of doses received as part of the multiple-dose series, participants were required to be continuously enrolled for at least 1 year prior to and at least 2 years following the date of the first dose of varicella, hepatitis A, or hepatitis B vaccination. Dates of first vaccination thus ranged from 1996 to 2002, with follow-up through 2004.
Vaccination Data
Outcome Measures
Covariate Data
Statistical Analysis
A total of 16 075 participants received a first dose of varicella vaccine, 594 917 received a first dose of hepatitis A vaccine, and 590 445 received a first dose of hepatitis B (Table 1). Two sites contributed most (80%–90%) of the data. About half of all vaccine recipients were female, the mean duration of MCO enrollment was about 9 years, and most vaccines were received by children and adolescents. Because of the age study criteria, those receiving the hepatitis A vaccine tended to be younger and those receiving the varicella vaccine were older. Most first doses of hepatitis A were received later in the study period (2000–2002), more hepatitis B was received in the earlier study years (1996–2000), and the proportion of first varicella doses received was similar across all study years.
Compliance With the Varicella Vaccine Series Among those aged 13 years and older who initiated the varicella vaccine series, only 36% to 56% received the second dose within 1 year, depending on age (Table 2). Over 40% of persons never received the second dose, and only a relatively small proportion completed the series more than 1 year after receipt of the first dose. Full compliance increased with age and was highest among adults aged 30 to 49 years (Table 2), a trend that was consistent across sites with adult data (see figure 2, available as a supplement to the online version of this article at http://www.ajph.org). Compliance also varied by site, particularly among adolescents: 24% to 60% for 13- to 17-year-olds, 48% to 60% for 18- to 29-year-olds, and 54% to 63% for 30- to 49-year-olds. Higher compliance was also observed for women, for those with 12 or more years of MCO enrollment, and in earlier study years (Table 3).
Compliance With the Hepatitis A Vaccine Series Among those who received a first dose of hepatitis A vaccine, the proportion who received the second dose within 1 year ranged from 40% to 50% in most age groups (Table 2). However, younger adults were less compliant, with only 25% of 18- to 29-year-olds and 35% of 30- to 49-year-olds completing the series within 1 year, and this effect was consistent across adult sites (see figure 2, available online). In contrast to what was found with varicella vaccine, most adolescents who did not complete the series within 1 year eventually received the second dose during the study period. As with varicella vaccine, most adults who did not receive a second dose within 1 year never received the dose within the study period. Full compliance with the hepatitis A series also varied by site (Table 3; see also figure 2, available online); however, sites with the lowest hepatitis A vaccine compliance were not the same as those with the lowest varicella vaccine compliance. Full compliance also increased with duration of MCO enrollment, number of medical visits in the year prior to the first dose, and calendar year of the first dose (Table 3).
Compliance With the Hepatitis B Vaccine Series
Compliance Among Medicaid Recipients
First to Last Dose Interval Among Vaccine Series Completers
In this large, population-based study of older children, adolescents, and adults, we found that compliance with multiple-dose varicella, hepatitis A, and hepatitis B vaccine series was low, particularly among adolescents, young adults, and those of low socioeconomic status as defined by receipt of Medicaid benefits. Rates of completion of all required vaccine doses within 1 year of the first dose were highest for hepatitis B vaccine (55%–65% in most age groups), whereas hepatitis A and varicella vaccine compliance was lower (40%–50% for most age groups), even though those vaccination series require only 2 doses. Even among the relatively modest proportion of individuals who ultimately received the recommended number of doses, the interval between series initiation and completion was long (1–2 years or more) for many persons, especially children and adolescents, leaving many undervaccinated and thus at higher risk for disease for extended time periods. These results, which indicate poor compliance in our study population of insured individuals enrolled in MCOs, are especially concerning because rates could be even lower among those with more limited access to health care. In addition to age and socioeconomic status, full compliance with multiple-dose vaccine series among older children, adolescents, and adults increased modestly with duration of MCO enrollment and the number of medical visits in the year prior to the first dose, and it varied by MCO site, although the trends in compliance rates across sites differed depending on the vaccine, with some sites demonstrating high levels of compliance for 1 vaccine series but not for others. The association between calendar year and compliance also varied by vaccine; compliance rates decreased over time for varicella and increased for hepatitis A and B vaccines. Other measured factors, including gender and the presence of a chronic condition, were not consistently associated with multiple-dose compliance for the vaccines we studied. The lowest rates of completion of multiple-dose vaccine series within 1 year (25%–35%) were observed among adolescents and Medicaid recipients for varicella vaccine and among younger adults for the hepatitis A vaccine series. These rates were unexpectedly low, and the reasons for such low compliance were unclear and therefore warrant further investigation. In particular, that over half of adolescents who initiated the varicella vaccine series never received a second dose is concerning. In light of the low levels of compliance in these subgroups and in our study population in general, further efforts that focus on increasing completion rates among those who initiate the series should be made. Possible approaches include improving immunization tracking systems and developing methods for following up on undervaccinated individuals.
Comparisons to evidence from other settings The limited data that are available, however, are consistent with our main finding that compliance is suboptimal in these age groups. Several studies that collected survey data with provider-verified immunization histories have found that the rates of 2-dose hepatitis A vaccine completion among older children and adolescents who initiate the series is modest (63%–69%),28–30 even in the context of an aggressive community-based vaccination intervention.30 Estimated rates of hepatitis B series completion among adolescents have varied from 45% to 73%, depending on the population and study design,31,32 with some of the highest rates achieved only after allowing longer follow-up, sending postcard reminders, and offering a reimbursement incentive.32 In contrast to the low compliance with multiple-dose vaccine series observed in our study and by previous studies with older children, adolescents, and adults, compliance with infant vaccination series is markedly higher.20 Factors probably facilitating compliance for infant vaccinations include routine well-child visits, a good understanding of universally recommended vaccination schedules by pediatric medical providers, high parental awareness of the importance of vaccination, and external requirements such as school entry laws and Healthcare Effectiveness Data and Information Set (HEDIS) measurements. Conversely, potential compliance barriers among older children, adolescents, and adults include lack of routine medical visits, lack of prioritization of vaccination relative to other medical care, population mobility, lack of a medical home, a relative lack of familiarity by patients and medical staff with the recommended schedules (since these vaccinations are often not given as part of a universal schedule), lack of tracking by health systems and, with the exception of hepatitis B vaccine for adolescents, lack of inclusion of such vaccinations as part of HEDIS measures or other quality assurance activities.30,33–36
Strengths and Limitations
Conclusions
The study received institutional review board approval from all participating sites.
Peer Reviewed J. C. Nelson and L. A. Jackson conceptualized the study. J. C. Nelson supervised the data analyses, which were conducted by R. C. L. Bittner and S. Zhao. All authors assisted with the study design, data acquisition and interpretation, and writing and critical revision of the article. Accepted for publication November 10, 2008.
1. Centers for Disease Control and Prevention. Prevention of varicella: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 1996;45(RR-11):1–36.[Medline] 2. Centers for Disease Control and Prevention. Prevention of hepatitis A through active or passive immunization: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 1996;45(RR-15):1–30.[Medline] 3. Centers for Disease Control and Prevention. Recommendation of the Immunization Practices Advisory Committee (ACIP). Inactivated hepatitis B virus vaccine. MMWR Morb Mortal Wkly Rep. 1982;31(24):317–322, 327–318.[Medline] 4. Centers for Disease Control and Prevention. Hepatitis B virus: a comprehensive strategy for eliminating transmission in the United States through universal childhood vaccination. Recommendations of the Immunization Practices Advisory Committee (ACIP). MMWR Recomm Rep. 1991;40(RR-13):1–25.[Medline] 5. Markowitz LE, Dunne EF, Saraiya M, Lawson HW, Chesson H, Unger ER. Quadrivalent human papillomavirus vaccine: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2007;56(RR-2):1–24.[Medline] 6. Clemens R, Safary A, Hepburn A, Roche C, Stanbury WJ, Andre FE. Clinical experience with an inactivated hepatitis A vaccine. J Infect Dis. 1995;171(suppl_1):S44–S49.[Web of Science][Medline] 7. McMahon BJ, Williams J, Bulkow L, et al.. Immunogenicity of an inactivated hepatitis A vaccine in Alaska Native children and Native and non-Native adults. J Infect Dis. 1995;171(3):676–679.[Web of Science][Medline] 8. Ashur Y, Adler R, Rowe M, Shouval D. Comparison of immunogenicity of two hepatitis A vaccines—VAQTA and HAVRIX—in young adults. Vaccine. 1999;17(18):2290–2296.[CrossRef][Web of Science][Medline] 9. Balcarek KB, Bagley MR, Pass RF, Schiff ER, Krause DS. Safety and immunogenicity of an inactivated hepatitis A vaccine in preschool children. J Infect Dis. 1995;171(suppl 1):S70–S72.[Web of Science][Medline] 10. Horng YC, Chang MH, Lee CY, Safary A, Andre FE, Chen DS. Safety and immunogenicity of hepatitis A vaccine in healthy children. Pediatr Infect Dis J. 1993;12(5):359–362.[Web of Science][Medline] 11. Horng YC, Chang MH, Lee CY, Safary A, Andre FE, Chen DS. Safety and immunogenicity of hepatitis A vaccine in healthy adult volunteers. J Gastroenterol Hepatol. 1993;8(4):338–341.[CrossRef][Web of Science][Medline] 12. Coates T, Wilson R, Patrick G, Andre F, Watson V. Hepatitis B vaccines: assessment of the seroprotective efficacy of two recombinant DNA vaccines. Clin Ther. 2001;23(3):392–403.[CrossRef][Web of Science][Medline] 13. Leroux-Roels G, Abraham B, Fourneau M, De Clercq N, Safary A. A comparison of two commercial recombinant vaccines for hepatitis B in adolescents. Vaccine. 2000;19(7–8):937–942.[CrossRef][Web of Science][Medline] 14. Andre FE. Summary of safety and efficacy data on a yeast-derived hepatitis B vaccine. Am J Med. 1989;87(3A):14S–20S.[Medline] 15. Zajac BA, West DJ, McAleer WJ, Scolnick EM. Overview of clinical studies with hepatitis B vaccine made by recombinant DNA. J Infect. 1986;13(suppl A):39–45.[CrossRef][Web of Science][Medline] 16. Kuter BJ, Ngai A, Patterson A, et al.. Safety, tolerability, immunogenicity of two regimens of Oka/Merck varicella vaccine (Varivax) in healthy adolescents and adults. Oka/Merck Varicella Vaccine Study Group. Vaccine. 1995;13(11):967–972.[CrossRef][Web of Science][Medline] 17. Gershon AA, Steinberg SP, LaRussa P, Ferrara A, Hammerschlag M, Gelb L. Immunization of healthy adults with live attenuated varicella vaccine. J Infect Dis. 1988;158(1):132–137.[Web of Science][Medline] 18. Centers for Disease Control and Prevention. National Immunization Survey home page. Available at: http://www.cdc.gov/nis. Accessed May 1, 2008. 19. Centers for Disease Control and Prevention. Vaccination coverage among adolescents aged 13–17 years—United States, 2007. MMWR Morb Mortal Wkly Rep. 2008;57(40):1100–1103.[Medline] 20. Centers for Disease Control and Prevention. National Health Interview Survey home page. Available at: http://www.cdc.gov/nchs/nhis.htm. Accessed May 1, 2008. 21. Centers for Disease Control and Prevention. Behavioral Risk Factor Surveillance System home page. Available at: http://www.cdc.gov/brfss. Accessed May 1, 2008. 22. International Classification of Diseases, Ninth Revision, Clinical Modification. Hyattsville, MD: National Center for Health Statistics; 1980. DHHS publication PHS 80-1260. 23. DeStefano F. The Vaccine Safety Datalink project. Pharmacoepidemiol Drug Saf. 2001;10(5):403–406.[CrossRef][Web of Science][Medline] 24. Lumley T, Kronmal RA, Ma S. Relative Risk Regression in Medical Research: Models, Contrasts, Estimators and Algorithms. Seattle: University of Washington; 2006. UW Biostatistics Working Paper Series, paper 293. Available at: http://www.bepress.com.offcampus.lib.washington.edu/uwbiostat/paper293. Accessed July 19, 2006. 25. Sansom S, Rudy E, Strine T, Douglas W. Hepatitis A and B vaccination in a sexually transmitted disease clinic for men who have sex with men. Sex Transm Dis. 2003;30(9):685–688.[CrossRef][Web of Science][Medline] 26. Campbell JV, Garfein RS, Thiede H, et al.. Convenience is the key to hepatitis A and B vaccination uptake among young adult injection drug users. Drug Alcohol Depend. 2007;91(suppl 1):S64–S72.[CrossRef][Web of Science][Medline] 27. Macdonald V, Dore GJ, Amin J, van Beek I. Predictors of completion of a hepatitis B vaccination schedule in attendees at a primary health care centre. Sex Health. 2007;4(1):27–30.[CrossRef][Web of Science][Medline] 28. Owen EC, Peddecord KM, Wang WW, et al.. Hepatitis A vaccine uptake in San Diego County: Hispanic children are better immunized. Arch Pediatr Adolesc Med. 2005;159(10):971–976. 29. Fiore A, Baxter LC, Bell BP, et al.. Hepatitis A 2004 vaccination in children: methods and findings of a survey in two states. Am J Prev Med. 2007;33(4):346–352.[CrossRef][Web of Science][Medline] 30. Bardenheier B, Gonzalez IM, Washington ML, et al.. Parental knowledge, attitudes, and practices associated with not receiving hepatitis A vaccine in a demonstration project in Butte County, California. Pediatrics. 2003;112(4):e269. 31. Gonzalez IM, Averhoff FM, Massoudi MS, et al.. Hepatitis B vaccination among adolescents in 3 large health maintenance organizations. Pediatrics. 2002;110(5):929–934. 32. Middleman AB, Robertson LM, Young C, Durant RH, Emans SJ. Predictors of time to completion of the hepatitis B vaccination series among adolescents. J Adolesc Health. 1999;25(5):323–327.[CrossRef][Web of Science][Medline] 33. Centers for Disease Control and Prevention. Hepatitis B vaccination coverage among adults—United States, 2004. MMWR Morb Mortal Wkly Rep. 2006;55(18):509–511.[Medline] 34. Rand CM, Shone LP, Albertin C, Auinger P, Klein JD, Szilagyi PG. National health care visit patterns of adolescents: implications for delivery of new adolescent vaccines. Arch Pediatr Adolesc Med. 2007;161(3):252–259. 35. Humiston SG, Rosenthal SL. Challenges to vaccinating adolescents: vaccine implementation issues. Pediatr Infect Dis J. 2005;24(6 suppl):S134–S140.[CrossRef][Web of Science][Medline] 36. Bloom HG, Wheeler DA, Linn J. A managed care organization's attempt to increase influenza and pneumococcal immunizations for older adults in an acute care setting. J Am Geriatr Soc. 1999;47(1):106–110.[Web of Science][Medline] 37. Mullooly J, Drew L, DeStefano F, et al.. Quality of HMO vaccination databases used to monitor childhood vaccine safety. Vaccine Safety DataLink Team. Am J Epidemiol. 1999;149(2):186–194.
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