APPROVED BY NVAC - December 2, 2004
Influenza is the nation's largest vaccination effort. Each year more Americans are vaccinated for influenza than for any other disease. Although vaccine shortages and delays have garnered much attention during the past several years, it is important also to highlight the success of the program. Millions of persons are vaccinated in a short time period each year; good collaboration exists between public and private sectors, which have documented an ability to respond appropriately to vaccine supply problems and other events; health care providers and the public have acted responsibly in targeting vaccine to those who need it most at times of shortage. Nevertheless, one cannot underestimate the importance and impacts of vaccine supply shortages, particularly that occurring for the 2004-05 season. A sufficient and predictable vaccine supply is critical for a successful prevention program and uncertainties jeopardize the ability to plan and make program improvements. Several interventions have been implemented to reduce the risk of future supply disruptions and strengthen influenza vaccine security for annual disease and as a component of preparedness for an influenza pandemic.
Even during seasons of adequate influenza vaccine supply, disease prevention is far from optimal. With an estimated average of 36,000 influenza-related deaths.1 and over 200,000 hospitalizations annually in the United States,2 influenza causes more mortality and morbidity than all other vaccine preventable diseases combined. While coverage rates for pediatric vaccines generally exceed 90%, of the more than 185 million persons recommended for annual influenza vaccine, fewer than half are vaccinated.
In 2004, the Acting Assistant Secretary for Health, Department of Health and Human Services (DHHS) requested that the National Vaccine Advisory Committee (NVAC) evaluate strategies and capabilities to improve influenza prevention in the U.S. An NVAC Influenza Vaccine Working Group evaluated both published and unpublished data and held discussions with stakeholders, including industry, public health officials, providers, purchasers, and consumers to develop recommendations.
Working Group recommendations are based on three overarching findings:
- The current influenza vaccine is not optimally effective among some groups recommended for vaccination or during every influenza season
- Current influenza vaccination recommendations are likely not optimal to prevent disease and death.
- In any given year, the majority of people for whom influenza vaccine is recommended do not get vaccinated.
Based on these findings, the Working Group developed several recommendations by which to improve influenza prevention in the United States:
- Improve vaccination coverage among recommended groups by facilitating the delivery of influenza vaccines in a range of settings, especially in "medical homes,", other medical sites, workplaces, and community sites where people have not previously had access to vaccination
- Make influenza vaccine purchase less of a burden and financial risk for providers.
- Explore options for a comprehensive vaccination program for adults.
- Increase the rate of influenza vaccination among health care workers.
- Consider expanding influenza vaccination recommendations.
- Implement systems to better understand the burden of influenza illness in the U.S. and to better assess the impact of vaccination programs and vaccine effectiveness
- Conduct a comprehensive review of the influenza research program to identify gaps and areas for additional support.
The CDC and its Advisory Committee on Immunization Practices (ACIP) recommends annual influenza vaccinations for persons at increased risk of severe influenza infection, their close contacts, and all health care workers.3 Influenza vaccination uptake increased dramatically through the 1990's. However, since the late 1990s, only about 80 million of the 185 million people for whom the vaccination is recommended are vaccinated in a typical influenza season.3 Vaccination coverage falls far short of the goals established by the DHHS in the Healthy People 2010 (HP 2010) objectives,4 which include influenza vaccine coverage of 90% among of adults aged 65 and older, children between 6 and 23 months of age, and persons in long-term institutional care or nursing homes; and 60% coverage in non-institutionalized adults who are less than 65 years old and have medical conditions that place them at increased risk of mortality and serious morbidity.3 Although influenza vaccine supply disruptions have affected the amount or timeliness of vaccine availability in recent years, even when vaccine supply is adequate there is no evidence of a trend toward higher vaccine coverage.5 This suggests that, in the absence of substantial systematic changes, HP 2010 coverage goals will not be met.
One question that must be asked is: will meeting influenza vaccine coverage goals lead to the substantial reduction in influenza disease and death, as has been seen with the pediatric vaccination program? For every routinely recommended childhood vaccine, when coverage rates have exceeded 90%, reductions in disease have been for similar or greater magnitude.6 By contrast, the impact of increased influenza vaccination coverage under current recommendations is likely to be of a lesser magnitude. The effectiveness of inactivated influenza vaccine depends primarily on the age and immunocompetence of the vaccine recipient and the degree of similarity between the viruses in the vaccine and those in circulation. Influenza vaccines must be changed annually to match the strains that are predicted to circulate in the population during the influenza season. In most years the match is good, but occasionally vaccine does not match the circulating strain and vaccine effectiveness is diminished, as occurred during the 2003-04 season,7,8.
When the match is good, influenza vaccine prevents influenza illness among approximately 70%--90% of healthy adults aged less than 65 years.9-14 and vaccination of healthy adults has resulted in decreased work absenteeism and decreased use of health-care resources, including the use of antibiotics.12,13 Older persons and persons with certain chronic diseases might develop lower post-vaccination antibody titers than healthy young adults and thus can remain susceptible to influenza.15-17 Among elderly persons 65 years and older not living in nursing homes or chronic-care facilities, influenza vaccine is 30%--70% effective in preventing hospitalization for pneumonia and influenza diagnoses.18,19 Among older nursing home residents aged 65 years and older, influenza vaccine can be 50%--60% effective in preventing hospitalization or pneumonia and 80% effective in preventing death, although the effectiveness in preventing influenza illness often ranges from 30% to 40%.20,21
In spite of numerous studies demonstrating effectiveness in small settings, national trend data raise questions regarding the overall impact of the current influenza vaccination program under current recommendations in reducing mortality. During the past several decades, as annual influenza vaccine use increased from about 20 million doses in the 1980s to the current total of about 80 million doses per year, there has not been a commensurate decrease in influenza mortality.22 Even when controlling for the aging of the U.S. population, expected program impacts have not been observed. In addition, the risk of mismatch between vaccine and circulating strains and the suboptimal vaccine effectiveness, particularly in high risk populations, suggest that research is needed to develop better influenza vaccines that can provide improved prevention.
The fragility of the U.S. influenza vaccine supply threatens the ability to implement an effective vaccination program, to increase coverage, and to prevent disease. Rates and severity of influenza disease vary annually, affecting demand. Against this backdrop, production issues in recent years have led to delays, spot shortages, and the substantial shortfall expected for the 2004-05 influenza season. Yet, in other years, there has been significant excess vaccine, and millions of vaccine doses have not been administered. 23 Even in 2003-04, when the combination of early widespread influenza outbreaks, coupled with the reports of influenza-related deaths in children led to increased demand for inactivated influenza vaccine, several million doses of a newly licensed and more expensive live, attenuated influenza vaccine (FluMistŪ) went unused. Because vaccine supply and investments into the development of new technologies are related to the size and predictability of the market and vaccine price, there is an intrinsic relationship between vaccine recommendations and program implementation and vaccine supply and research. Thus, although the NVAC Working Group recommendations do not directly focus on vaccine supply, their implementation would have a major and positive impact on vaccine supply, uptake and on investments in new vaccines and technologies.
At the request of the Acting Assistant Secretary for Health, Dr. Cristina Beato, NVAC established a Working Group to evaluate strategies to reduce the impact of influenza disease in the U.S. and make recommendations on how to substantially improve influenza prevention and reduce disease burden. The Working Group was encouraged to ask challenging questions and consider new strategies, paradigms, infrastructures, and technologies as well as incremental changes that could be made to the current system. In February 2004, the NVAC Influenza Working Group was appointed, chaired by Dr. Charles Helms, current NVAC Chair. The Working Group was divided into three subgroups to focus on separate key issues:
- The Influenza Vaccine Delivery, Financing, and Demand Subgroup was chaired by Dr. Fernando Guerra. This subgroup examined private and public delivery systems, communications issues, and vaccine demand.
- The Influenza Vaccine Recommendations and Strategies Subgroup was chaired by Dr. Jerome Klein. This subgroup studied issues related to the measurement of the burden of disease, the impact of the vaccination program, and vaccine efficacy; and the considering consideration of alternative vaccine recommendations.
- The Influenza Vaccine Research, Development, and Production Subgroup was chaired by Dr. Ann Arvin. This subgroup assessed the influenza vaccine research and development enterprise in the public and private sectors.
During the spring of 2004, the subgroups reviewed published and unpublished data, consulted with DHHS agencies and their advisory committees, influenza vaccine manufacturers, clinicians, professional and advocacy associations, researchers, vaccine distributors, and health care providers to thoroughly review the program. Based on these investigations the subgroups developed key findings and recommendations which were presented and discussed at the NVAC meetings in June and October 2004. This report was developed following those discussions and was approved by the Committee for presentation to the Acting Assistant Secretary for Health in December 2004.
Recommendations and Rationales
Vaccine Financing and Demand
Improve vaccination coverage among recommended groups by facilitating the delivery of influenza vaccines in a range of settings, especially in "medical homes," other medical sites, workplaces, and community sites where people have not previously had access to vaccination.
Rationale: Several barriers exist to achieving high rates of influenza vaccine coverage among recommended groups through vaccination at primary -care provider physicians offices.24,25 While children commonly make routine age-based well child care visits, most adults seek health care only in the context of an acute or chronic illness. In this setting, there is unlikely to be time or focus on delivery of preventive services such as vaccination. Many women receive their primary care from gynecologists and some persons with chronic illness receive primary care from sub-specialists, both of whom may be less likely to deliver vaccinations.26,27 Financial barriers also may decrease the likelihood that vaccination will be provided by primary-care physicians.24
To increase influenza vaccine coverage, effective strategies must be implemented to increase vaccination at other sites where adults receive health care or where preventive services could be delivered.28,29 Every contact with the health care system should be used as an opportunity to vaccinate.30, Emergency departments, which are increasingly being used as sources of care by the poor and underinsured, may be cost-effective sites for delivering preventive services such as vaccination and preventing future hospitalization among the most medically and socially vulnerable.31,32 A strategy of routinely offering influenza vaccination in emergency rooms to patients between September and December (and later if vaccine supply allows) could markedly decrease missed opportunities for vaccination.(CDC unpublished data)
Provision of vaccination at places not used for health care, such as work sites, grocery stores, pharmacies, shopping malls, detention centers, and other places where people can conveniently be reached during the months before influenza season has been shown to increase vaccination coverage among groups who do not usually receive influenza vaccination.33 Increasing vaccination at these sites requires overcoming barriers that may include limits on who can administer vaccinations and the need for a physician's order before vaccination. The use of "standing orders" avoids the need for individual physician's orders and has been effective in increasing vaccination at sites outside of provider offices.34,35 Development of toolkits that include model standing orders and other materials to facilitate vaccination at alternate sites, active distribution of these materials and promotion of program goals, and active follow-up are needed for effective implementation. Resources to coordinate these programs should be made available to State and local immunization programs.
Make influenza vaccine purchase less of a burden and financial risk for providers.
Rationale: Studies have shown that providers have concerns regarding the costs of purchasing and administering influenza vaccine and their level of reimbursement. Health plan payment rates may not adequately compensate for these costs, and, for many providers, influenza vaccination is a financial loss. When all costs for influenza vaccine, its administration, office staff time, and practice overhead are compared with average Medicare immunization reimbursement payments of $17.76 in 2003, one study indicates that providers' per-shot losses range from $3.36 to $32.76.36 A recent CMS proposal to increase reimbursement for influenza vaccine administration from $8 to $18 will significantly improve the financial balance for office based vaccination; however, in some settings, the balance will still remain negative. In addition, providers must order and purchase vaccine months before it is administered resulting in a substantial capital outlay. Finally, manufacturers have adopted a "no return" policy for influenza vaccine; thus providers are wary about potentially ordering excess vaccine and receiving no reimbursement for unused product. Given these factors, there has been little incentive for health care providers to increase coverage rates for influenza vaccination within a practice. Because private insurers generally have followed the lead of Medicare in reimbursement policy, the recent policy change by CMS to increase influenza vaccination coverage may increase the use of influenza vaccination by providers nationwide. Further consideration with CMS of financial issues for providers may be an efficient and effective approach to identify additional solutions.
Explore options for supporting a comprehensive vaccination program for adults.
Rationale: Financial barriers limit health care providers' willingness and ability to increase influenza vaccination among adults. Costs also may limit the willingness of persons in recommended groups to be vaccinated in the absence of health insurance or when reimbursement does not cover all costs. Studies have shown a 10-30% increment in coverage when vaccine is provided without charge to patients.37-40 In Ontario, Canada the combination of free vaccine and a universal recommendation has resulted in 77% coverage among the elderly (about 10% better than in the U.S.) and 42% coverage in the entire population of the province.
Cost may be a substantial barrier particularly among persons who are poor, uninsured, or disabled. In 2000, only two state Medicaid programs met standards for a comprehensive adult immunization policy, which includes: covering ACIP recommended vaccines; permitting only a nominal co-pay; providing vaccine replacement; and allowing separate billing for vaccine administration. One option to improve on this would be to establish a comprehensive program nationwide, focusing on the poor and uninsured, and analogous to the Vaccines for Children program, but other approaches also may be envisioned. A systematic evaluation of options that includes discussion with stakeholder groups could provide information to DHHS that can lead to policy decisions.
Increase the rate of annual influenza vaccination among health care workers.
Rationale: Despite longstanding recommendations for vaccination of health care workers, many still do not get vaccinated. Vaccination of health care workers (HCWs) has been shown to prevent mortality in their patients41 as well as reduce influenza infection and absenteeism in the HCWs9 themselves and may sometimes result in financial savings to the sponsoring health institutions.9 Despite this, only 38% of HCWs received influenza vaccine the previous year according to the 2002 National Health Interview Survey 3. Federal advisory committees including the Advisory Committee on Immunization Practices (ACIP) and NVAC have highlighted the need to improve vaccine uptake in this recommended group. As is the case for the general public, making receipt of influenza vaccine convenient and eliminating costs to HCWs are effective interventions, particularly when combined with comprehensive programs to increase influenza vaccination coverage. Reducing barriers to vaccination may be particularly important in settings such as nursing homes where many HCW salaries are low and where residents are at highest risk for severe and fatal influenza. As professional organizations and advisory committees emphasize the importance of recommendations for HCW vaccination, and health care organizations implement programs to improve influenza vaccination coverage, identifying successful strategies, promoting large scale organizational change, and monitoring coverage all are important.
Influenza Burden and Program Impacts
Develop a Working Group to consider critical issues and barriers to expanded influenza vaccination recommendations and to propose solutions.
Rationale: The current burden of influenza related deaths and hospitalizations, despite increased vaccine coverage over the past decades, raises questions about program effectiveness and impact. This has led to an evaluation of influenza prevention strategies including the possible need to expand vaccination recommendations. Expanded vaccination recommendations that include school-aged children, for example, could enhance protection of older adults and those at high risk of serious illness by decreasing transmission of disease within families and communities. In addition, vaccine recommendations based on age groups may be more effectively implemented than current recommendations to vaccinate only persons with high-risk medical conditions among those between two and 49 years of age.
U.S. vaccination recommendations are made by the Centers for Disease Control and Prevention, based on advice from the Advisory Committee on Immunization Practices (ACIP). In February 2004, the ACIP Influenza Working Group began an evaluation of a possible expansion of influenza vaccination recommendations. Expanding vaccination recommendations raises important issues including the capability of our immunization system to implement a broader program and achieve high vaccination coverage, the capability of our vaccine supply system to reliably produce the doses necessary, and the Nation's ability to finance vaccination and achieve equitable implementation among the economically disadvantaged. The NVAC will continue to work closely with the ACIP as expanded influenza vaccination recommendations are considered.
Vaccine supply can be a critical barrier to expanding influenza vaccination recommendations. Current production capacity is insufficient to support a substantial increase in vaccine use. Continued efforts are needed to promote expanded production capacity and diversification of supply across more manufacturers and technologies to support increased annual vaccination under current or expanded recommendations.
The ability to effectively deliver vaccine under expanded vaccination recommendations also is important. One likely target for vaccination will be school-aged children, yet this population is not targeted by current vaccine recommendations and the ability to achieve high coverage in this group has not been documented. Strategies for vaccination of school aged children and adolescents need to be defined and evaluated, both because of their importance for implementation of expanded influenza vaccination recommendations and because many of the vaccines currently being developed also will focus on this population. Given that traditional vaccination delivery using needle and syringe may be unwieldy and unpopular in school aged populations, new delivery systems such as nasal spray or a transcutaneous patch should be assessed. The experience gained during the introduction of the live, attenuated influenza vaccine (FluMistŪ) into the U.S. market in 2003-2004 and the lessons from the launch of this product should be examined.
Implement systems to better understand the burden of influenza illness in the U.S. and to better assess program impacts and vaccine effectiveness.
Rationale: Annual influenza vaccine use in the U.S. has increased from about 10 million doses in 1976, at the time of the swine influenza scare, to about 80 million doses in recent years. Despite this increase, influenza is estimated to cause an average of 36,000 deaths and over 200,000 hospitalizations each year.1,2 Ecological or trend studies have suggested that increased vaccination coverage has not been accompanied by similar increases in preventing death, even when controlling for the aging of the U.S. population. By contrast, epidemiological studies using other methods to evaluate the impact of vaccine have shown significant effectiveness for disease and death outcomes.42 Reconciling the differences in study results is important in considering possible new influenza vaccine recommendations and whether alternative vaccination strategies are needed.
The conflicting results of epidemiological studies and the need to estimate influenza related hospitalization and death by modeling also highlight the current inability to directly assess influenza disease burden and measure vaccination program impacts. Efforts to characterize the impacts of the vaccination program on influenza are hampered by several factors: annual variations in influenza outbreaks, which make tracking disease trends difficult; the absence of a unique clinical influenza syndrome and lack of an etiological diagnosis in most persons with febrile or respiratory illness; and the contribution of influenza in exacerbating non-respiratory illnesses such as acute myocardial infarction or congestive heart failure. While influenza surveillance systems in the U.S. have been developed to monitor annual spread, causative strains, and location and timing of an outbreak, directly assessing disease burden, program impacts, and annual vaccine effectiveness have not been primary objectives.
New sentinel surveillance systems should be implemented to help fill this gap. One approach is to directly measure hospitalizations from influenza disease in facilities where etiological diagnosis is enhanced, and to link these data with vaccination rates among patients and in the surrounding community. A pilot program using this approach in children has been implemented in three metropolitan areas. Surveillance of pediatric populations is particularly important as new recommendations for universal vaccination of children between six and 23 months old were adopted in 2004 and further expansions of the vaccination program are being considered. Strategies to directly assess influenza disease and program impacts also should be implemented among adults. CDC recently has begun a project to assess vaccine effectiveness during the influenza season based on rapid analysis of an administrative managed care database.
Conduct a comprehensive review of the influenza research program to identify gaps and areas for additional support.
Rationale: Scientific research leads to the development of tools that make effective disease prevention possible. New diagnostic tests using molecular approaches can improve surveillance and assessment of program impacts. Genomic analysis of influenza strains identified globally and studies of how disease spreads from animals to humans and between human populations can provide critical information that will improve the ability to predict what strains will emerge and should be included in vaccines. This expanding database of genomic information should be made available to the research community.
An improved understanding of immune mechanisms of protection against influenza, immune response in young infants, and changes in immunity that occur with aging can lead to development of better prevention strategies in vulnerable populations. Improved methods to develop vaccine reference strains and process development improvements can increase the speed and volume of vaccine production. Development of new vaccine delivery systems can increase the safe mass delivery of influenza vaccine. Research on new influenza vaccines may lead to vaccines that accelerate the immune response to the first dose, which is important during a rapidly moving epidemic. Research to improve vaccine immunogenicity may yield ways to provide better protection in elderly and high risk populations or provide more long-lasting protection so that annual vaccine no longer would be needed.
A wide range of influenza disease and prevention related research is being supported and conducted by multiple agencies in the public and private sectors. An influenza research program review that describes ongoing activities, defines key objectives, and identifies gaps in the research portfolio is an important first step in strengthening the program and providing the techniques and tools that will improve the ability to prevent the most common and most deadly of all vaccine preventable diseases in the United States.
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- Thompson WW, Shay DK, Weintraub E, Brammer L, Bridges CB, Cox NJ et al. Influenza-associated hospitalizations in the United States. JAMA. 2004; 292:1333-1340.
- Harper SA, Fukuda K, Uyeki TM, Cox NJ, Bridges CB. Prevention and control of influenza: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2004; 53:1-40.
- U.S.Department of Health and Human Services. Healthy People 2010. 2nd ed. U.S. Government Printing Office 2000, 2000.
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- Assessment of the effectiveness of the 2003-04 influenza vaccine among children and adults--Colorado, 2003. MMWR Morb Mortal Wkly Rep. 2004; 53:707-710.
- Preliminary assessment of the effectiveness of the 2003-04 inactivated influenza vaccine--Colorado, December 2003. MMWR Morb Mortal Wkly Rep. 2004; 53:8-11.
- Wilde JA, McMillan JA, Serwint J, Butta J, O'Riordan MA, Steinhoff MC. Effectiveness of influenza vaccine in health care professionals: a randomized trial. JAMA. 1999; 281:908-913.
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