Executive Summary
In September 2014, the Assistant Secretary for Health (ASH) asked the National Vaccine Advisory Committee (NVAC) to conduct an independent mid-course review to evaluate the progress on the goals of the National Vaccine Plan and develop recommendations for the ASH. This NVAC review considers the findings of a parallel, separate mid-course review of the status of the National Vaccine Plan commissioned by the National Vaccine Program Office (NVPO) in August 2015 that included a broad stakeholder engagement process. This report provides the NVAC conclusions and recommendations. The NVAC supports the NVPO Mid-course Review report findings and its focus on the following 5 priority opportunity areas for advancing US vaccine and immunization efforts: (1) “strengthen health information and surveillance systems to track, analyze, and visualize disease, immunization coverage, and safety data, both domestically and globally; (2) foster and facilitate efforts to strengthen confidence in vaccines and the immunization system to increase coverage rates across the lifespan; (3) eliminate financial and systems barriers for providers and consumers to facilitate access to routine, recommended vaccines; (4) strengthen the science base for the development and licensure of vaccines; and (5) facilitate vaccine development.”1 The NVAC agrees with the focus in the NVPO report on these 5 opportunity areas but also recommends that, if additional funding or other resources become available, the ASH and other federal agencies should continue to support the following other opportunity areas in the NVPO Mid-course Review report: (1) “increase coordination, collaboration, and knowledge sharing among related parties and disciplines; (2) improve the transparency of the vaccine safety system and the entire vaccine enterprise to policy makers, the public, and providers; (3) improve scientific knowledge about why and among whom vaccine adverse events occur; and (4) support the strengthening of immunization systems globally through policies, practices, and partnerships.”1
In this report, the NVAC outlines its assessment of what would constitute near-term success for each of the 5 opportunity areas and identifies indicators to use to measure success and monitor progress on the established target goals. Recognizing the limitations of existing indicators, the NVAC recommends the development of new indicators to improve tracking and analysis, especially for vaccine innovations.
The NVAC recommends the following:
The ASH should charge the NVPO, in coordination with relevant departments and agencies, to adopt existing indicators (eg, Healthy People 2020 indicators) to track progress on the National Vaccine Plan goals and to prepare an annual report to the ASH and the NVAC on progress.
The ASH should charge the NVPO, in coordination with relevant departments and agencies, to develop and validate new indicators within each of the 5 opportunity areas to ensure improved tracking of goals. The new indicators should include one that will track and report on US government annual financial investments in vaccine innovation that support the development of (1) vaccines for established pathogens that have no vaccines, (2) vaccines for emerging pathogens, and (3) improved existing vaccines. The new indicators should also consider investments in vaccine delivery technologies.
The ASH should continue to strongly support US contributions to global immunization efforts and the integration of global immunization efforts into the opportunity areas as appropriate.
The NVPO should continue to implement the recommendations from previous NVAC reports, such as the 2015 report, Assessing the State of Vaccine Confidence in the United States.2 By doing so, the NVPO can highlight NVAC recommendations related to implementing the priorities outlined in the NVPO 2010 Mid-course Review. The NVPO should use the framework defined in this report to make further advancements under the existing 2010 National Vaccine Plan for both domestic and global immunization outcomes.
The ASH should charge the NVPO to develop the 2020 National Vaccine Plan, which should incorporate the findings in this report, and consider the impact of health care disparities on implementation and achievement of the objectives of the 2020 Plan.
The ASH should charge the NVPO, in coordination with other relevant departments and agencies, to begin developing strategies to (1) identify priorities for US government investments in vaccine-related innovations and (2) overcome barriers that inhibit innovation.
National Vaccine Advisory Committee
Chair
Kimberly M. Thompson, ScD, University of Central Florida College of Medicine, Orlando, FL
Designated Federal Official
Bruce G. Gellin, MD, MPH, National Vaccine Program Office, US Department of Health and Human Services, Washington, DC
Public Members
Steven Black, MD, Cincinnati Children’s Hospital, Cincinnati, OH
Jay C. Butler, MD, Alaska Department of Health and Social Services, Division of Public Health, Juneau and Anchorage, AK
Melody Anne Butler, RN, BScN, Good Samaritan Hospital Medical Center, Lindenhurst, NY
Sarah Despres, JD, Pew Charitable Trusts, Washington, DC
David Fleming, MD, PATH, Washington, DC
Ann Ginsberg, MD, PhD, Aeras, Rockville, MD
Robert H. Hopkins, Jr, MD, University of Arkansas for Medical Sciences, Little Rock, AR
Ruth Lynfield, MD, Minnesota Department of Health, St Paul, MN
Yvonne Maldonado, MD, Stanford University School of Medicine, Stanford, CA
Saad Omer, PhD, MBBS, MPH, Emory University, Atlanta, GA
Wayne Rawlins, MD, MBA, ConnectiCare, Hartford, CT
Mitchel C. Rothholz, RPh, MBA, American Pharmacists Association, Washington, DC
Nathaniel Smith, MD, MPH, Arkansas Department of Health, Little Rock, AR
Representative Members
Philip Hosbach, Sanofi Pasteur, Swiftwater, PA
Timothy Cooke, PhD, NovaDigm Therapeutics, Grand Forks, ND
National Vaccine Advisory Committee (NVAC) Mid-course Review (MCR) Working Group
MCR Working Group Chairs
Yvonne Maldonado, MD, Stanford University School of Medicine, Stanford, CA
Nathaniel Smith, MD, MPH, Arkansas Department of Health, Little Rock, AR
NVAC Members
Timothy Cooke, PhD, NovaDigm Therapeutics, Grand Forks, ND
Sarah Despres, JD, Pew Charitable Trusts, Washington, DC
Ann Ginsberg, MD, PhD, Aeras, Rockville, MD
Philip Hosbach, Sanofi Pasteur, Swiftwater, PA
Ruth Lynfield, MD, Minnesota Department of Health, St Paul, MN
Wayne Rawlins, MD, MBA, ConnectiCare, Hartford, CT
US Department of Health and Human Services, National Vaccine Program Office Staff and Technical Advisors
Anju Abraham, MPH, MS, National Vaccine Program Office, US Department of Health and Human Services, Washington, DC
Bruce G. Gellin, MD, MPH, National Vaccine Program Office, US Department of Health and Human Services, Washington, DC
Jennifer Gordon, PhD, National Vaccine Program Office, US Department of Health and Human Services, Washington, DC
Introduction
Preventing disease and promoting health depend on the collaboration of several sectors of society. Over decades of collaborative work, the US vaccine and immunization system accomplished one of the greatest public health achievements in the 20th century.3 Immunization provides significant health and economic benefits. A 2013 study performed by the Centers for Disease Control and Prevention (CDC) estimated that routine childhood immunizations prevented 322 million illnesses and averted 732 000 premature deaths from vaccine-preventable illnesses in children born between 1994 and 2013, with an estimated societal cost savings of $1.38 trillion.4 A 2016 study reported that investments in immunization in low- and middle-income countries for 2011-2020 will yield an estimated return of approximately 16 times the cost.5
In 1986, the Public Health Service Act §300aa–et seq created the National Vaccine Program as a way to integrate the numerous federal agencies and offices that work with each other and nonfederal stakeholders on vaccine development, production, and delivery.6 The legislation called for the development of a strategic plan to “establish priorities in research and the development, testing, licensing, production, procurement, distribution, and effective use of vaccines, describe an optimal use of resources to carry out such priorities, and describe how each of the various departments and agencies will carry out their vaccine functions.”6 The strategic plan, developed and maintained by the NVPO and called the National Vaccine Plan, provides strategic direction for all US vaccine- and immunization-related activities. It aims to create a robust and coordinated system to prevent infectious diseases through vaccination. The most recent version, the 2010 National Vaccine Plan, provides a detailed 10-year roadmap to unify and strengthen all aspects of the US vaccine and immunization enterprise. It sets out 5 overarching goals: (1) “develop new and improved vaccines; (2) enhance the vaccine safety system; (3) support communications to enhance vaccine decision-making; (4) ensure a stable supply of, access to, and better use of recommended vaccines in the United States; and (5) increase global prevention of death and disease through safe and effective vaccination.” The National Vaccine Plan further defines the 5 goals by providing additional supporting objectives and strategies.7
The National Vaccine Implementation Plan, released in spring 2012, outlines federal activities conducted in support of the National Vaccine Plan priorities.8 However, the National Vaccine Implementation Plan recognizes the need to incorporate flexibility that allows the plan to adapt to changes in vaccination technologies and health care delivery models and to unforeseen contingencies that require changes to the National Vaccine Plan. Therefore, the National Vaccine Implementation Plan encompasses only activities for the first 5 years of the National Vaccine Plan (ie, 2010-2015). The National Vaccine Implementation Plan called for a formal mid-course review of the 2010 National Vaccine Plan, with guidance from the National Vaccine Advisory Committee (NVAC).8
The NVPO Mid-course Review, performed between September 2014 and September 2016, included an extensive stakeholder engagement process and disseminated a report in November 2016.1 The NVPO report does not replace the National Vaccine Plan. Instead, it aims to identify and highlight areas of greatest opportunity (ie, opportunity areas) to make critical advancements in the vaccine and immunization enterprise, and it evaluates and defines priorities to guide implementation activities for the near term (2016-2020).1 The opportunity areas represent a consensus of stakeholders on how to focus federal priorities in light of changing and uncertain budgets and political environments. The NVPO report1 also summarizes indicators identified by the stakeholders as the best measures of the success of current efforts and tools to inform the next iteration of the National Vaccine Plan (ie, the 2020 National Vaccine Plan).
In March 2016, the Assistant Secretary for Health (ASH) requested that the NVAC provide an independent, parallel mid-course review of the National Vaccine Plan. This report presents the NVAC’s conclusions and recommendations. The report also highlights nuances for the interpretation of the 5 opportunity areas and explores indicators used to define success and monitor progress. The report recommends broader considerations for the implementation of the National Vaccine Plan going forward, including the need to develop new indicators.
Process
The NVAC builds on input collected during the stakeholder engagement process and the findings described in the NVPO report.1 Briefly, between September and December 2015, nonfederal and federal stakeholders provided input on the accomplishments and remaining gaps of the 2010 National Vaccine Plan, and they developed opportunity areas for advancing the National Vaccine Program during the remaining 5 years of the plan, 2016-2020. Between February and April 2016, federal and nonfederal stakeholders participated in focus groups and interviews to prioritize the opportunity areas.1 The NVPO report1 identifies 9 consensus opportunity areas that 3 focus groups ranked according to priority (Table 1).1 These opportunity areas included: (1) strengthen health information and surveillance systems to track, analyze, and visualize disease, immunization coverage, and safety data, both domestically and globally; (2) foster and facilitate efforts to strengthen confidence in vaccines and the immunization system to increase coverage rates across the lifespan; (3) eliminate financial and systems barriers for providers and consumers to facilitate access to routinely recommended vaccines; (4) strengthen the science base for the development and licensure of vaccines; (5) facilitate vaccine development; (6) increase coordination, collaboration, and knowledge sharing among related parties and disciplines; (7) improve the transparency of the vaccine safety system and the entire vaccine enterprise to policy makers, the public, and providers; (8) improve scientific knowledge about why and among whom vaccine adverse events occur; and (9) support the strengthening of immunization systems globally through policies, practices, and partnerships.
Table 1.
Stakeholder rankings of 9 opportunity areas to advance the National Vaccine Program (adapted from the NVPO Mid-course Review of the 2010 National Vaccine Plan), 2015a
| Opportunity Area | Rank |
|---|---|
| Strengthen health information and surveillance systems to track, analyze, and visualize disease, immunization coverage, and safety data, both domestically and globally.b | 1 |
| Foster and facilitate efforts to strengthen confidence in vaccines and the immunization system to increase coverage rates across the lifespan. | 2 |
| Eliminate financial and systems barriers for providers and consumers to facilitate access to routinely recommended vaccines. | 3 |
| Strengthen the science base for the development and licensure of vaccines. | 4 |
| Facilitate vaccine development. | 5 |
| Increase coordination, collaboration, and knowledge sharing among related parties and disciplines. | 6 |
| Improve the transparency of the vaccine safety system and the entire vaccine enterprise to policy makers, the public, and providers. | 7 |
| Improve scientific knowledge about why and among whom vaccine adverse events occur. | 8c,d |
| Support the strengthening of immunization systems globally through policies, practices, and partnerships. | 9d |
aAdapted from the NVPO Mid-course Review of the 2010 National Vaccine Plan.1
bA 10th opportunity area in the NVPO report1 (ie, improve surveillance for vaccine-preventable diseases, and strengthen health information systems to monitor vaccine coverage, effectiveness, and safety, both domestically and globally) overlaps with this opportunity area and does not appear in this table.
cMost focus group participants grouped this opportunity area into opportunity area 4 (ie, implicit in opportunity area 4).
dThese opportunity areas are ranked similarly.
Between March and October 2016, the NVAC independently evaluated the information collected during the NVPO focus groups and the findings in the NVPO report.1 The NVAC also gathered information from nonfederal stakeholders representing 2 consumer groups and from federal stakeholders not included in the NVPO focus groups. In December 2016, the NVAC invited and received public comments on a draft of the report. The NVAC findings in this report should help to define the activities needed to achieve success in the opportunity areas and the indicators needed to measure progress during the remaining time horizon of the 2010 National Vaccine Plan.
General Findings
Overall, the NVAC agrees with the identification and prioritization of opportunity areas in the NVPO report.1 The NVAC also agrees that the top 5 most highly ranked opportunity areas correctly represent activities likely to yield the greatest impact during the next 5 years (Table 1). These top 5 opportunity areas include:
Strengthen health information and surveillance systems to track, analyze, and visualize disease, immunization coverage, and safety data, both domestically and globally.
Foster and facilitate efforts to strengthen confidence in vaccines and the immunization system to increase coverage rates across the lifespan.
Eliminate financial and systems barriers for providers and consumers to facilitate access to routinely recommended vaccines.
Strengthen the science base for the development and licensure of vaccines.
Facilitate vaccine development.
The NVAC acknowledges the need to identify priorities for vaccination activities. Future funding remains uncertain and limited, and the greatest public health impact will likely come from carefully targeting available resources. On the other hand, the NVAC also recognizes the importance of the other 4 opportunity areas and recommends that the ASH and federal partners not lose the opportunity to support them if additional funding or other resources become available.
The NVAC recognizes that highlighting US domestic efforts may risk losing the momentum to advocate for US global immunization efforts, which reduce the potential for importations of diseases into the United States. The NVAC notes that strengthening routine immunization systems in the United States and abroad helps protect the American population from the importation of vaccine-preventable diseases by ensuring access globally to safe and effective vaccines. The NVAC suggests that, when appropriate, domestic implementation activities related to the 5 prioritized opportunity areas should tie directly to global activities. The NVAC agrees with the NVPO report1 that indicators used to measure progress should reflect progress of both US domestic and global immunization goals, because the expertise, technical support, and capabilities needed to achieve domestic and global objectives often overlap. The NVPO report1 includes global indicators developed for the Global Vaccine Action Plan (GVAP)9 by the World Health Organization (WHO) Strategic Advisory Group of Experts (SAGE),10 which the NVAC recognizes as supporting the importance of the national commitment to global immunization.11
The NVAC highly values stakeholder engagement processes, like the one used to prioritize the opportunity areas in the NVPO report.1 The NVAC also acknowledges that individual participants in focus groups may introduce bias and the results may not be representative. Accordingly, the NVAC suggests that future implementation activities should consider all of the opportunity areas and regularly assess the impact of the activities on all populations. The NVAC recognizes that the impact of health care disparities among different stakeholder groups should be assessed regularly, particularly among populations at risk. Notably, implementation activities should particularly consider populations at risk, because focusing on these potentially underrepresented groups may help to address overarching health care and access disparities that may prohibit achieving the objectives of the 2010 National Vaccine Plan.
NVAC Analysis and Discussions of Opportunity Areas
For each of the 5 prioritized opportunity areas, the NVAC discusses what it would mean to achieve success, including what success would look like in the near term and what challenges could impede success. The NVAC also discusses possible indicators to track progress. To the extent possible, the NVAC suggests the use of existing indicators, such as those already used by US government agencies like the Healthy People 2020 (HP2020) indicators.12 However, the NVAC notes that many of the existing indicators do not provide the flexibility needed to fully track the opportunity areas. Where existing indicators do not provide the information needed to mark progress for an opportunity area, the NVAC provides suggestions for other more appropriate indicators. In some cases, no appropriate indicators currently exist, and the NVAC suggests the development of new indicators. However, the time needed to develop new indicators will likely exceed the time frame of the National Vaccine Plan and require additional resources. Accordingly, the NVAC includes these indicators as recommended actions for future updates to the National Vaccine Plan.
Opportunity Area 1: Strengthen Health Information and Surveillance Systems to Track, Analyze, and Visualize Disease, Immunization Coverage, and Safety Data, Both Domestically and Globally
The use of health information technologies and data from patient electronic health records (EHRs) for improving health care quality and supporting public health continues to increase.1 The NVPO report1 recognizes that the use of health information systems represents the greatest opportunity to significantly advance the goals of the National Vaccine Plan over the coming years. Broadening the use and interoperability of health information technologies across a variety of platforms, providers, and public health agencies may provide near–real-time data for surveillance and allow the identification of trends in disease incidence, vaccination coverage, vaccine effectiveness, and vaccine safety. Improved data quality and sharing may also facilitate outbreak response efforts13 and improve patient access to recommended vaccines by preventing missed opportunities to vaccinate.2,14–16 Efforts to improve data systems should include making the data easily and widely accessible to stakeholders that may improve implementation of the 2010 National Vaccine Plan and future updates. In addition, emerging technologies such as 2-dimensional barcodes, which contain scannable information about the product identifier, lot number, and expiration date, improve (1) tracking of vaccination coverage and safety and (2) the management of vaccine inventory and supply.
Ongoing NVAC discussions continue to focus on the opportunities to strengthen interoperability and data exchange among patient EHRs, immunization information systems (IISs), and different public health jurisdictions.17 While a number of efforts at both the federal and nonfederal levels include addressing barriers to interoperability and use of IISs,18–21 the NVAC notes that success will depend on continued efforts to characterize the technical, legal, and policy challenges to cross-jurisdictional data exchange.17 Previous NVAC recommendations supported the implementation of policies and practices that can facilitate the uniform, reliable, secure exchange of immunization and health data, such as defining standardized data submission elements and developing template legal agreements and memoranda of understanding between jurisdictions.17,22
Health information technologies can help monitor vaccination coverage, vaccine effectiveness, and immunization safety.23,24 Federal vaccine safety monitoring systems, such as the Post-licensure Rapid Immunization Safety Monitoring and Vaccine Safety Datalink, use patient information from EHRs to identify potential adverse events following immunization.25,26 A 2014 NVAC report, Reducing Patient and Provider Barriers to Maternal Immunizations, encourages federal partners to identify ways to optimize the use of EHR and IIS data for monitoring and surveillance of vaccination coverage and vaccine safety for mother-infant pairs following the administration of recommended vaccines during pregnancy.27
Important opportunities exist to strengthen infectious disease surveillance using EHRs and electronic laboratory reporting. Advances in diagnostic technologies continue to improve our understanding of pathogens, and the collection and integration of these data represent an important opportunity to better track diseases and the value of vaccines. Currently, most disease surveillance depends on passive reporting of reportable diseases by states. Surveillance through automated processes that extract information from EHRs and electronic laboratory reports provides more complete data on infectious disease trends. For example, electronic surveillance of vaccine-preventable diseases significantly improves monitoring of vaccine effectiveness and provides information about shifts in the prevalence of disease caused by vaccine serotypes versus non-vaccine serotypes of pneumococcal disease.28 For diseases such as those caused by respiratory syncytial virus (RSV), electronic surveillance data may provide better clarity on the disease burden among varying age groups and inform the design of clinical trials of new vaccines. Currently, the lack of standards for data submission across EHRs and electronic laboratory reporting systems remains a significant barrier to collecting automated data for nationwide surveillance. Despite some progress, barriers continue to exist due to variation among states in their capabilities, the electronic systems used for disease surveillance, and the inability to integrate and share public health data.29 Challenges also remain with respect to making the existing data easily and widely available. Recognizing the opportunities afforded by the availability of integrated electronic data, the NVAC summarized characteristics for near-term success and challenges to achieving this success for opportunity area 1 (Table 2).
Table 2.
National Vaccine Advisory Committee characteristics of near-term success and potential challenges in opportunity areas for advancing vaccine and immunization efforts in the United States, 2015
| Opportunity Area | Characteristics of Near-term Success in This Opportunity Area | Challenges in Achieving That Success |
|---|---|---|
| 1. Strengthen health information and surveillance systems to track, analyze, and visualize disease, immunization coverage, and safety data, both domestically and globally. |
|
|
| 2. Foster and facilitate efforts to strengthen confidence in vaccines and the immunization system to increase coverage rates across the lifespan. |
|
|
| 3. Eliminate financial and systems barriers for providers and consumers to facilitate access to routinely recommended vaccines. |
|
|
| 4. Strengthen the science base for the development and licensure of vaccines. |
|
|
| 5. Facilitate vaccine development. |
|
|
Abbreviations: EHR, electronic health record; IIS, immunization information system; NRA, national regulatory authority.
aIncreased coordination and expansion of health care and community immunizer activities.
Proposed indicators for opportunity area 1
The NVPO report provides 3 domestic and 1 global existing indicators for this opportunity area. The NVAC recommends the same global indicator for this opportunity area as recommended in the NVPO report (Table 3).1 The domestic indicators in the NVPO report1 include: (1) the number of meaningful use adopters that opt to fulfill the electronic reporting to IIS requirements to obtain meaningful use certification, (2) percentage of adults aged >19 years who have 1 or more immunizations recorded in an IIS, and (3) an increase in the percentage of children aged <6 years whose immunization records are in a fully operational, population-based IIS tracked by the Office of the National Coordinator for Technology (ONC) and the Centers for Medicare & Medicaid Services (CMS). The NVAC suggests that these indicators do not fully address the many complexities of this opportunity area. For example, the NVPO report1 does not capture any indicators to mobilize additional efforts around the use of health information technologies to support comprehensive, standardized, real-time electronic laboratory reporting on the incidence of vaccine-preventable diseases. Indicators currently tracked by the ONC, CDC, and GVAP serve as benchmarks of near-term success for this opportunity area (Table 3). The NVAC also proposes the development of new domestic indicators that may further inform the planning of implementation activities in this opportunity area (Table 4).
Table 3.
Proposed indicators for tracking success in opportunity areas advancing vaccine and immunization efforts in the United States, 2015
| Opportunity Area | Existing Indicators | Baseline | Target |
|---|---|---|---|
| 1. Strengthen health information and surveillance systems to track, analyze, and visualize disease, immunization coverage, and safety data, both domestically and globally. | Percentage of office-based physicians electronically sharing patient information with any providers outside their organization (domestic) | 38% (2015)a | Increasing trend |
| Percentage of health care providers electronically sharing patient information with their state IIS (eg, meaningful use requirement) (domestic) | 73% of eligible hospitals in the United States reported vaccination to their local IIS (2014)b | Increasing trend | |
| Percentage of laboratory reports received electronically annually for notifiable conditions (domestic) | 67% (2014)c | 100% | |
| 2. Foster and facilitate efforts to strengthen confidence in vaccines and the immunization system to increase coverage rates across the lifespan. | Decrease the percentage of children in the United States who receive 0 doses of recommended vaccines by age 19 to 35 months (domestic) | 0.8% (2012)d | Target not set (informational) |
| Percentage of states reporting kindergarten coverage data based on census (domestic) | 58% (2014)d | Increasing trend | |
| Percentage of countries responding to the question on the top 3 reasons for vaccine hesitancy (indicator 1) in 2014 (global) | 73% (2014)e | Increasing trend | |
| Percentage of countries that have assessed the level of hesitancy in vaccination at the national or subnational level in the past 5 years (global) | 29% (2014)e | Increasing trend | |
| 3. Eliminate financial and systems barriers for providers and consumers to facilitate access to routinely recommended vaccines. | Percentage of surveyed primary care providers who stock vaccines routinely recommended for adults (domestic) | 20% internists and 31% family practices (2012)f | 60% |
| Percentage of states and territories that allow pharmacists to administer all routinely recommended vaccines for adults aged >19 without a patient-specific prescription (domestic) | 85% (2013)g | 100% | |
| Percentage of state Medicaid programs that provide coverage of all Advisory Committee on Immunization Practices/CDC-recommended vaccinations for adults and prohibit cost sharing (domestic) | 20% (2012)h | 100% | |
| Increase the percentage of adults who are vaccinated against zoster (shingles) (domestic) | 6.7% (2008)i | 30% | |
| Increase coverage with the recommended number of doses of human papillomavirus vaccine for females by age 13 through 15 (domestic) | 28.1% (2012)j | 80% | |
| Percentage of pregnant women who report receiving influenza immunization during pregnancy (domestic) | 52% (2013)k | Not defined | |
| Number of WHO regions achieving measles elimination by 2020 (global) | 0/5 WHO regions (2010)l | 6 WHO regions | |
| Dropout rates between the first and third dose of diphtheria, tetanus, and pertussis (DTP) (global) | 18.6% member states with dropout rates ≥10% (2012)m | Decreasing trend | |
| Number of countries reaching vaccination coverage targets through routine services (global) | 129 countries vaccinated at least 90% of their children with DTP (2014)e | By 2020, reach coverage of 90% nationally and 80% in every district for all recommended vaccines in national programs | |
| 4. Strengthen the science base for the development and licensure of vaccines. | Licensure and launch of vaccine or vaccines against one or more major currently non–vaccine-preventable diseases (global) | Not applicable (2015)10 | Progress toward licensure/launch of one or more such vaccines by 2020 |
| 5. Facilitate vaccine development. | Licensure and launch of at least one platform delivery technology (global) | Not applicable (2015)10 | 1 or more vaccines by 2020 |
| Number of vaccines that either have been relicensed or have been licensed for use in a controlled-temperature chain at temperatures above the traditional 2°C-8°C range (global) | Not available10 | Increasing trend | |
| Immunization programs have sustainable access to predictable funding, high-quality supply, and innovative technologies: number of vaccine delivery technologies (devices and equipment) that have received WHO prequalification (global) | 284 products (2015)10 | Increasing trend |
Abbreviations: CDC, Centers for Disease Control and Prevention; IIS, immunization information system; WHO, World Health Organization.
aOffice of the National Coordinator for Health Information Technology. Health IT Dashboard: office-based physician health IT adoption. 2015. https://dashboard.healthit.gov/apps/physician-health-it-adoption.php. Accessed May 8, 2017.
bOffice of the National Coordinator for Health Information Technology. Health IT Dashboard: hospital selection of meaningful use public health measures: eligible hospitals reporting to the Medicare EHR incentive program for fiscal year 2014. https://dashboard.healthit.gov/quickstats/pages/FIG-Hospital-Selection-Public-Health-Measures.php. Published 2014. Accessed May 8, 2017.
cLamb E, Satre J, Pon S, et al. Update on progress in electronic reporting of laboratory results to public health agencies—United States, 2014. MMWR Morb Mortal Wkly Rep. 2015;64(12):328-330.
dHill HA, Elam-Evans LD, Yankey D, Singleton JA, Kolasa M. National, state, and selected local area vaccination coverage among children aged 19-35 months—United States, 2014. MMWR Morb Mortal Wkly Rep. 2015;64(33):889-896.
eWorld Health Organization. Global Vaccine Action Plan: Monitoring, Evaluation & Accountability Secretariat Annual Report 2015. Geneva, Switzerland: World Health Organization; 2015.
fHurley LP, Bridges CB, Harpaz R, et al. U.S. physicians’ perspective of adult vaccine delivery. Ann Intern Med. 2014;160(3):161.
gAmerican Pharmacists Association, National Alliance of State Pharmacy Associations. Pharmacist administered vaccines: types of vaccines authorized to administer. 2013. http://www.pharmacist.com/sites/default/files/PharmacistIZAuthority.pdf. Accessed May 8, 2017.
hStewart AM, Lindley MC, Chang KHM, Cox MA. Vaccination benefits and cost-sharing policy for non-institutionalized adult Medicaid enrollees in the United States. Vaccine. 2014;32(5):618-623.
iLu PJ, Euler GL, Harpaz R. Herpes zoster vaccination among adults aged 60 years and older, in the U.S., 2008. Am J Prev Med. 2011;40(2):e1-e6.
jCurtis CR, Yankey D, Jeyarajah J, Dorell C, Stokley S. National and state vaccination coverage among adolescents aged 13-17 years—United States, 2012. MMWR Morb Mortal Wkly Rep. 2013;62(34):685-693.
kDing H, Black CL, Ball S, et al. Influenza vaccination coverage among pregnant women—United States, 2013-14 influenza season. MMWR Morb Mortal Wkly Rep. 2014;63(37):816-821.
lWorld Health Organization. Annex 6: The Monitoring and Evaluation/Accountability Framework. Geneva, Switzerland; World Health Organization; 2012. http://www.who.int/immunization/global_vaccine_action_plan/GVAP_Annex6.pdf. Accessed May 8, 2017.
mWorld Health Organization. Global Vaccine Action Plan: Monitoring, Evaluation & Accountability Secretariat Annual Report 2013. Geneva, Switzerland: World Health Organization; 2013. http://www.who.int/immunization/global_vaccine_action_plan/GVAP_secretariat_report_2013.pdf. Accessed May 8, 2017.
Table 4.
Proposed opportunity area indicators for future development of vaccine and immunization efforts in the United States, 2015
| Opportunity Area | Proposed Indicators for Future Development | What Indicator Will Measure |
|---|---|---|
| 1. Strengthen health information and surveillance systems to track, analyze, and visualize disease, immunization coverage, and safety data, both domestically and globally. | Number of operational memoranda of agreement between state and territorial IISs | Progress toward interoperability of IISs |
| Percentage of providers using 2-dimensional barcodes to populate EHRs and IISs | More accurate collection of data on immunization safety, efficacy, and coverage | |
| Number/percentage of case reports received electronically by local or state health departments | Capability of states to collect data for surveillance and reporting | |
| Number of disease surveillance systems interoperable with corresponding IISs | Capability to link information about vaccination status to disease surveillance information | |
| 2. Foster and facilitate efforts to strengthen confidence in vaccines and the immunization system to increase coverage rates across the lifespan. | Track state legislation on nonmedical exemptions to determine number of states that offer nonmedical exemptions and ease of obtaining such exemptions in each statea | Policies that influence vaccine confidence |
| Development of a validated index, comprising a number of individual and social dimensions, to measure vaccine confidence and capable of: (1) rapid, reliable, and valid surveillance of national vaccine confidence; (2) detection and identification of variations in vaccine confidence at the community level; and (3) diagnosis of the key dimensions that affect vaccine confidence | Validated measures to evaluate vaccination confidence related to intervention strategies, determine best practices for all ages, and provide information about differences among vaccines | |
| Development of measures and methods to analyze the mass-media environment and social media conversations about vaccine confidencea | Identified topics of concern to parents, health care providers, and members of the public | |
| Track state legislation on nonmedical exemptions to determine number of states that offer nonmedical exemptions and ease of obtaining such exemptions in each statea | Policies that influence vaccine confidence | |
| 3. Eliminate financial and systems barriers for providers and consumers to facilitate access to routinely recommended vaccines. | Percentage of providers not providing immunization services for their patients (year-on-year trends for subgroups of provider types [ie, pediatricians, obstetricians, gynecologists]) | Continuing barriers to providers to offer immunization services in their practices |
| Number of countries that eliminated rubella | Global measure of access, equity, and strength of routine immunization systems | |
| 4. Strengthen the science base for the development and licensure of vaccines. | US government annual spending on vaccine research and development | US government investments in vaccine research and development |
| 5. Facilitate vaccine development. | A mechanism to track the vaccine development pipeline that includes a specific number of target, priority pathogens | The robustness of the clinical pipeline to support eventual approval of vaccines against priority pathogens |
Abbreviations: EHR, electronic health record; IIS, immunization information system.
aLanguage adapted from the National Vaccine Advisory Committee report Assessing Vaccine Confidence in the United States.2
Additional considerations for opportunity area 1
A 2013 NVAC report, Enhancing the Work of the Department of Health and Human Services National Vaccine Program in Global Immunization,11 provides analyses highlighting remaining opportunities to strengthen vaccine-preventable disease surveillance efforts and pharmacovigilance at the global level. Unfortunately, few countries currently maintain the surveillance or laboratory capabilities needed to accurately measure the burden of vaccine-preventable diseases or the impact of vaccines on reducing morbidity and mortality in their populations. Most countries lack the critical infrastructure to monitor, assess, and respond to vaccine safety signals.11 Global surveillance activities outlined in the 2010 National Vaccine Plan play an important role in justifying the development and introduction of new and improved vaccines. The NVAC continues to strongly encourage efforts to integrate health information technologies that facilitate quality data collection domestically and globally to further strengthen immunization programs and vaccine pharmacovigilance.
Opportunity Area 2: Foster and Facilitate Efforts to Strengthen Confidence in Vaccines and the Immunization System to Increase Coverage Rates Across the Lifespan
National data continue to show that vaccination coverage among children 19 to 35 months of age remains high, and, in general, among American parents, childhood immunization remains the social norm.30 However, national discussion continues to grow about the attitudes and beliefs people hold and express regarding their confidence in the recommended vaccines and schedule. While many reasons may explain shifts in vaccine confidence, the success of implementing routine vaccine schedules and the resulting significant reductions in incidence continue to reduce the visibility of vaccine-preventable diseases. Unfortunately, even small increases in concerns about vaccination may result in decreasing vaccination rates, delays in receipt of immunizations, and the accumulation of populations of susceptible individuals within US communities. Underimmunization—including intentionally forgoing vaccines—can lead to serious public health consequences. For example, a nationwide measles outbreak in 2014-2015 that originated in California and involved a disproportionately high proportion of unvaccinated individuals (ie, 49 of 110 [45%] unvaccinated and 47% unknown or undocumented vaccination status) led to measles cases in 7 US states, Mexico, and Canada.31 Measles outbreaks in the United States continue to cause significant morbidity and lead to substantial costs for control.32
A 2015 NVAC report, Assessing the State of Vaccine Confidence in the United States,2 examines the determinants of vaccine acceptance among parents and recommends a number of strategies to improve parental confidence in vaccines. That report defines vaccine confidence as “the trust that parents or health-care providers have (1) in the recommended immunizations, (2) in the provider(s) who administers vaccines, and (3) in the process that leads to vaccine licensure and the recommended vaccination schedule.”2 The NVAC recognizes that vaccine acceptance remains a very complex issue with nuances that may play out differently at the federal, state, and local levels. Additional research and evaluation activities will be needed to develop evidence-based interventions to increase vaccine confidence in diverse populations and for different vaccines and vaccine formulations.
In contrast to the growing body of evidence about confidence regarding childhood and adolescent vaccinations, less evidence exists related to adult confidence in vaccinations. Vaccination coverage in adults remains very low for all recommended vaccines.33 A 2012 NVAC report, A Pathway to Leadership for Adult Immunization,34 highlights the lack of a “coordinated public health infrastructure to support an adult immunization program” (ie, no effort for adults exists comparable to the Section 317 Program and Vaccines for Children program) and recommends the development of a National Adult Immunization Program. The 2016 National Adult Immunization Plan35 includes 4 goals: (1) “strengthen the adult immunization infrastructure, (2) improve access to adult vaccines, (3) increase community demand for adult immunizations, and (4) foster innovation in adult vaccine development and vaccination-related technologies.” The NVAC emphasizes the need to further improve adult immunization. Some studies document misperceptions about vaccine safety and the effectiveness and benefits of vaccination, such as for influenza vaccine,36 but the role vaccine confidence plays in the uptake of adult vaccines generally remains unclear. Vaccine confidence also represents only one component of overall vaccine acceptance across the life course, and understanding the cumulative factors that lead to high vaccination coverage at all ages (eg, access, awareness of recommendations) will require further investigation.37
Vaccine confidence and consumer and health care provider trust in the entities that develop, license, recommend, and monitor vaccines, and in the vaccines themselves, represent issues of global concern. The SAGE issued a report to help characterize vaccine confidence (including the context of vaccine hesitancy and the consequences of hesitancy attitudes and beliefs on vaccine uptake) in different settings.38 Similar to the NVAC report Assessing the State of Vaccine Confidence in the United States,2 the SAGE recommendations called for the development of standardized, validated tools to help national immunization programs better understand factors that can lead to low vaccine confidence and low demand for immunization services. Characteristics of near-term success and associated challenges for opportunity area 2 are summarized (Table 2).
Proposed indicators for opportunity area 2
Currently, no validated methodologies exist for measuring and evaluating vaccine confidence.2 Healthy People 2020 objective IID-9 (ie, Decrease the percentage of children in the United States who receive zero doses of recommended vaccines by age 19 to 35 months)39 tracks data on children who remain completely unvaccinated. The NVPO report includes this objective as its only indicator for this opportunity area.1 Although this indicator does not reflect geographic variations or the factors that lead to unvaccinated children (eg, state and local policies and practices, access issues, poverty), until more precise indicators exist, the NVAC recognizes that this indicator may provide indirect evidence about nationwide trends in vaccine confidence (Table 3). In addition, the NVAC suggests using the number of states reporting kindergarten coverage data based on the US Census as an indication that may similarly provide indirect information about the quality of data available to track trends in vaccine confidence.
At the international level, the GVAP identifies the need for indicators for vaccine confidence to help benchmark progress toward the strategic objective that “individuals and communities understand the value of vaccines and demand immunization both as a right and a responsibility.”9 The NVAC notes the lack of standardized indicators and challenges faced by the GVAP in the development of appropriate indicators.10 This report includes the GVAP indicators on vaccine hesitancy, while emphasizing the need to create a framework for better understanding of vaccine confidence globally (Table 3). The success of this opportunity area depends on a better understanding of vaccine confidence at national and community levels, because attitudes and beliefs vary. The NVAC underscores the importance of developing indicators to better understand and more accurately assess vaccine confidence in the United States (Table 4). The 2015 NVAC report, Assessing the State of Vaccine Confidence in the United States,2 describes the characteristics of possible indicators for assessing vaccine confidence in the United States.
Additional considerations for opportunity area 2
Events such as the 2014-2015 measles outbreak in California, which included a relatively high fraction of intentionally unvaccinated individuals,31 raise issues about state policies on exemptions to school-entry laws. Discussions about this outbreak and the 2014-2015 exemption rates among kindergarteners in California motivate the NVAC to suggest the potential use of personal belief exemption rates as an indicator for measuring vaccine confidence.40 Data on the rate of nonmedical exemptions to school-entry laws may help public health authorities to correlate pockets of unvaccinated individuals with the incidence of vaccine-preventable disease outbreaks.41 However, states may not collect information about exemptions in a standardized way, which limits generalizability. For example, while an increasing number of states (ie, 32 of 51, 62%) collect data using a census-based method (eg, kindergarteners in all schools), some states continue to use a sample-based method (eg, some selected schools), voluntary response (eg, convenience reporting from schools), or a combination of methods.42 In addition, some states may allow or may require an exemption if a child missed a single dose of vaccine, even for a child otherwise up-to-date on other vaccines,42 and these differences create challenges for cross-state comparisons. Exemption rates do not necessarily provide a good indication of coverage, because parents may opt to file an exemption for convenience and then later go on to fully vaccinate their child. The enforcement of school-entry laws also differs substantially between and within states, and home-schooled children often remain outside of these laws, further complicating the interpretation of the data. The impact of home-schooled children remains unknown, but unvaccinated- and undervaccinated individuals may cluster and can contribute to outbreaks.43 Nonmedical exemptions may also reduce coverage without requiring caregiver education on the risks of children remaining unvaccinated.
Data on immunization exemptions can help to inform schools, parents, and public health programs about possible pockets of susceptible children. A number of entities track exemption legislation across jurisdictions, and the NVAC recognizes that keeping apprised of this information could inform the development and testing of strategies to improve vaccine confidence. The NVAC strongly encourages future activities to support the standardized collection of nonmedical exemption rates across states to help improve the utility of these data and highlights the important role that IISs may play in these efforts.
Opportunity Area 3: Eliminate Financial and Systems Barriers for Providers and Consumers to Facilitate Access to Routinely Recommended Vaccines
The NVAC appreciates the need to improve vaccination coverage across the lifespan by addressing access and financing issues that prevent patients from receiving recommended vaccines. Access to immunization services represents a multifaceted issue impacting vaccine coverage at both the domestic and global levels. Factors affecting access may include, for example, convenient access to immunization providers and the health care system, an adequate and available supply of vaccines, and freedom from financial barriers to vaccines and immunization services. Recent evidence suggests that disparities in immunization remain an issue, with children living below the federal poverty level reporting lower vaccination coverage.44 Despite the 1994 Vaccines for Children mandate,45 which makes recommended, routine childhood immunizations available at no cost to children who might not otherwise be vaccinated because of inability to pay, the United States still needs to address health disparities and correct inequities in immunizations.
The Affordable Care Act expands health insurance coverage and access to preventive services, including immunization, and it provides insurance to more than 16.4 million previously uninsured people in the United States as of August 2016.46 While the Affordable Care Act represents an important milestone for adult immunization in the United States, it does not completely eliminate financial barriers to immunization for consumers, and, as of early 2017, its future remains uncertain. Expanded access to immunizations should lead to increased demand by reducing financial barriers to vaccine providers, and it also creates the need for a more diverse array of provider types that can offer convenient immunization services.47
Provider ability and willingness to offer vaccines and immunization services lead to higher vaccination coverage. Multiple studies show patients are much more likely to receive vaccinations if their providers offer them at the time of their health care visit.33,48,49 However, offering immunization services in the office requires upfront investments by providers, including the cost to purchase vaccine products and equipment for proper storage and handling and the cost of managing vaccine inventories, counseling, and recording and reporting (eg, to the IIS). These potentially significant costs factor into the decision by providers to offer certain vaccines, along with concerns about fair and adequate payment from public and private payers for the administration of immunization services.47 Several NVAC reports document an urgent need to identify and improve upon current processes related to billing, coding, and payment for immunization services (including vaccine counseling and administration).27,43,50 Changing models of compensation continue to affect immunization rates and incentives for different types of vaccine providers. A 2009 NVAC report, Financing Vaccination of Children and Adolescents, recommends strategies to address the financial pressures on pediatric and adolescent vaccination practices.50 However, the recommendations do not cover the challenges of providing immunizations to adult populations. The NVAC appreciates the need for additional work to quantify the financial impact of issues that affect providers’ willingness to offer vaccines in their offices. Characteristics of near-term success and associated challenges for opportunity area 3 are summarized (Table 2).
Proposed indicators for opportunity area 3
The NVAC agrees with the indicators for this opportunity area in the NVPO report1 and includes the same indicators from the American Pharmacists Association, CDC, CMS, GVAP, and HP2020 for domestic and global indicators (Table 3). In addition, the NVAC included a GVAP indicator that tracks vaccination coverage targets. The NVAC proposes the development of 2 additional indicators for this opportunity area (Table 4).
Additional considerations for opportunity area 3
The NVAC suggests that in the context of the complex and dynamic payer environment, federal and state payers should increase their efforts to better align payment policies with public health priorities. Vaccination provides a well-recognized, cost-effective, and often cost-saving prevention strategy that yields significant benefits for pediatric and adolescent populations domestically4 and globally5 and could prevent significant costs associated with vaccine-preventable diseases in adults.51 Therefore, public payers should support the administration of all recommended vaccines for routine use for all ages by working to minimize the financial burden to patients and providers. At the global level, the Gavi Alliance and others should continue to support the expansion of immunization adoption and increased coverage.
The NVAC also supports more coordination and expansion of health care and community immunizer activities, also called the “immunization neighborhood,” to ensure that patients receive recommended vaccines and to improve access to recommended vaccines. For example, increasing coverage rates for human papillomavirus vaccine and expanding adult immunization coverage motivates greater consideration of opportunities in the immunization neighborhood.52 The NVAC continues to call for strategies to understand and overcome the barriers to receiving recommended vaccines from nonphysician vaccine providers (eg, pharmacists) and at nontraditional locations (eg, workplace, schools).15,16,27 The NVAC recognizes the need to monitor how changing models of compensation affect the immunization neighborhood. The NVAC further emphasizes that some communities, especially rural ones that lack convenient and affordable access to immunization services, continue to experience missed opportunities for immunization. State-to-state variability in immunization policies and practices further increases complexity in the current system.
Opportunity Area 4: Strengthen the Science Base for the Development and Licensure of Vaccines
The world lacks vaccines against many infectious diseases that impact public health, both in the United States and globally.53 Unfortunately, developing vaccines for poorly understood pathogens requires additional information about both the pathogen and the host immune response to optimally elicit a directed, protective response against specific antigens.54,55 This opportunity area aims at the development and licensure of new and improved vaccines to meet ongoing, emerging, and/or unmet public health needs. Scientific needs in this area include, for example, a better understanding of pathogen biology and host immune response, a better grasp of why vaccine adverse events occur, and identification of the correlates and surrogates of immune protection and other factors that can predict vaccine effectiveness and duration of protection among diverse populations.1 In addition to recognizing the importance of improving our understanding of immune responses to vaccines and correlates of protection, the NVAC emphasizes the need to identify appropriate mechanisms that will encourage data sharing among investigators related to optimizing the science base.
The NVAC recognizes the importance of strengthening the science base around vaccinology, the human immune response to vaccines (and how induced immunity compares to natural infection), and how improved understanding could help to foster innovation in vaccines far beyond the timeline of the National Vaccine Plan.56 Greater scientific knowledge about the immune response and surrogates of immune protection may aid in vaccine development by helping to more rapidly identify promising candidate vaccines. Greater knowledge may also provide a possible pathway to licensure in the context of limited feasibility of large-scale efficacy trials in some situations. For example, the unpredictable disease burden from year to year of pertussis makes it difficult to identify study populations for testing a new pertussis vaccine for use in the United States, and emerging infectious diseases like Ebola spread unpredictably such that testing vaccines may require innovative strategies.57 The NVAC highlights the importance of supporting translational research and its application to the development of vaccines for use in special populations, such as pregnant women,58 and of improving knowledge of immune responses in the elderly. For this opportunity area, the NVAC defines success as making scientific breakthroughs that result in vaccine candidates for pathogens with historically unsuccessful development pathways, such as human immunodeficiency virus (HIV), tuberculosis (TB), malaria, and several priority antibiotic-resistant pathogens. Characteristics of near-term success and associated challenges for opportunity area 4 are summarized (Table 2).
Additional considerations for opportunity area 4
New technologies continue to increase our knowledge and understanding of immune responses and correlates/surrogates of protection. Increasing the scientific knowledge base involves filling crucial knowledge gaps, harnessing the available data, and knowing how to best use them. The NVAC encourages the support of (1) collaborative efforts and partnerships to optimize the use of existing data to inform vaccine science and further vaccine development efforts and (2) meetings that review experience and catalyze efforts to identify and address gaps. The NVAC recognizes the importance of improving knowledge about the correlates of protection for vaccine development and suggests the development of a future indicator to track the availability of useful immunological correlates of protection to support future updates to the National Vaccine Plan. Additionally, as vaccine science evolves, all stakeholders will need to incorporate new knowledge into curricula in a timely fashion to ensure that health care professionals remain at the forefront of immunization knowledge.
Opportunity Area 5: Facilitate Vaccine Development
Recognizing unmet public health needs in the United States globally motivates the development of new or improved vaccines (eg, more effective, safer, higher-yield vaccines) and delivery strategies to support immunization as a primary prevention strategy. The NVAC recognizes the need to better understand the drivers of vaccine innovation and development and how to best support them. Barriers to vaccine development may include the lack of mechanisms to incentivize or support higher-risk vaccine research and investments by biotechnology and pharmaceutical companies.
The NVPO report1 noted the challenges associated with the lack of convergence of regulatory submission data requirements internationally, the need for funding and preparedness models for rapidly developing vaccines to address emerging diseases, the insufficient infrastructure to support clinical trials in low-resource settings, and inadequate support for crossing the financial challenges, or “valley of death,” between preclinical and clinical development. The NVAC emphasizes the importance of considering the entire vaccine development system in discussions related to providing incentives for vaccine development. For example, discussions around identifying barriers to vaccine development often center on mechanisms to incentivize innovation and vaccine development for larger pharmaceutical companies. However, different considerations may arise when discussing how to support translational research to bring vaccines to development from the perspective of smaller biotech companies. Financial incentives from governmental entities to minimize or share risk remain very important for supporting the success of some companies, while other companies may care more about regulatory certainty, regulatory consistency, and a ready market that would drive final development.
The NVAC further recognizes the importance of incentives that reward companies for the development of products with incremental but significant improvements over existing products (eg, improved effectiveness, products for a special population such as high-dose influenza vaccine for the elderly). New technologies, including adjuvants, vaccine vial monitors, and novel delivery strategies, offer vaccine innovation opportunities that could improve the effectiveness of existing vaccines, lower vaccine production costs, decrease wastage, and make vaccines easier to deliver and administer. However, the lack of recognition or distinction for these products as incrementally improved vaccines makes this type of product development difficult for companies to justify, given little or no additional return on investment for providing these products. Understanding the impact of this barrier on vaccine development warrants additional characterization; the NVAC suggests retrospective case studies or prospective studies to follow new product launches and the uptake of incremental products.
In addition to creating incentives to develop vaccines for established diseases that lack an effective vaccine (eg, RSV, HIV, TB), the 2014-2015 Ebola outbreak and the 2016 Zika outbreak further underscore the importance of the robustness of the vaccine development pipeline in the United States and international readiness levels to address emerging threats. In May 2016, the WHO released An R&D Blueprint for Action to Prevent Epidemics to provide technical guidance and coordination and to advocate for additional global resources to provide the necessary medical countermeasures to respond to and mitigate public health emergencies caused by emerging pathogens.59 This blueprint focuses on 3 main approaches: (1) improving coordination and fostering an enabling environment, (2) accelerating research and development (R&D) processes, and (3) developing new norms and standards tailored to the epidemic context.59 Activities include strengthening policies, partnerships, and capabilities both before and during an epidemic to minimize lives lost and economic disruptions due to infectious disease outbreaks.59 The NVAC encourages federal agencies to continue working with the broader global community to support a preparedness R&D plan that includes platform technologies or other strategies that will help to minimize the barriers and the time needed for the development and delivery of vaccine products against emerging pathogens. Lessons learned from Ebola and Zika medical countermeasure response efforts should inform the implementation of the WHO R&D Blueprint59 to better understand the capabilities and infrastructure needed to respond to future emerging pathogens.
The NVAC also appreciates the need to further explore the impact of vaccine pricing on vaccine manufacturing and supply. Vaccine development requires significant resource investments, and manufacturers must often choose between continuing vaccine development or focusing on products with a more certain return on investment.53 In addition, newer vaccines may require complex manufacturing techniques that can impact production capacity and supply.60 Manufacturers often build production facilities dedicated to the production of a single vaccine product to meet requirements for vaccine quality control and assurance, but this necessitates additional upfront costs that the producer must justify based on a reasonable expectation of multiple years of high vaccine demand. Lower vaccine prices impact investments in vaccine manufacturing and result in higher probabilities of vaccine shortages due to manufacturing problems.61 The NVAC suggests that the contribution of these factors to vaccine development barriers warrants further investigation.
Other issues such as country-level differences in regulatory requirements for the testing, licensure, manufacturing, and distribution of vaccine products, while common across the development pipeline, may affect stakeholders differently. While national regulatory authorities (NRAs) must consider national needs and comply with applicable laws and regulations pertaining to vaccine development and evaluation, global efforts to converge regulatory guidance and reviews among different NRAs may streamline the development of vaccines and, thus, may facilitate broader and faster introduction of vaccines globally. Characteristics of near-term success and associated challenges for opportunity area 5 are summarized (Table 2).
Proposed indicators for opportunity areas 4 and 5 combined
The NVPO report1 combines the indicators for opportunity areas 4 and 5 because “they speak to different challenges for the same issue: vaccine development.” Regarding opportunity area 4 (strengthen the science base for the development and licensure of vaccines), the NVAC recognizes that indicators to benchmark scientific progress remain very difficult to define and may not provide good information about success. Adequate, sustained funding levels represent a necessary but not sufficient requirement for attracting new talent, new ideas, and new innovations. Furthermore, the types of scientific questions that will lead to the development of new and improved vaccines represent high-risk/high-reward projects. The NVAC recognizes that tracking the total amount of funding toward specific scientific questions may not always translate into a direct path for the development of new vaccine candidates. For example, new evidence highlights that vaccine components in acellular vs whole-cell vaccines may contribute differently to immune response pathways,62,63 but uncertainty remains about how to best use this information to aid in the development of improved vaccine candidates.64 The NVAC notes the general unpredictability of steps forward in scientific knowledge and how they translate into returns on investment. Similarly, the NVAC does not expect that indicators based on the number of peer-reviewed journal articles on vaccine science would necessarily provide an accurate indicator of scientific advances that could lead to new vaccine development.
The NVPO report1 provides 3 indicators for opportunity areas 4 and 5 that focus on later-stage vaccine development: (1) “average vaccine development timeline from the preclinical phase to regulatory submission (domestic and global), (2) number of vaccines in phase I clinical trials for diseases for which no vaccines are currently on the market (the analysis will include the following infectious diseases: influenza [development of universal influenza vaccines], HIV/AIDS, malaria, and TB], and (3) licensure and launch of at least 1 platform delivery technology or the number of vaccine delivery technologies (devices and equipment) that have received WHO prequalification against the 2010 baseline (global).” Unfortunately, the NVPO report1 could not provide baseline values for the first 2 proposed indicators, which the NVAC views as not sufficiently established to represent current validated indicators. The NVAC proposes 4 global indicators developed by the GVAP,10 including 1 included in the NVPO report1 (Table 3).
The NVAC proposes the development of a domestic indicator for opportunity area 4 to improve tracking of vaccine R&D funding, vaccine delivery and administration, vaccine thermostability, and US technical readiness to respond to emerging infectious disease threats (Table 4). The NVAC recommends that the NVPO begin a process to define and develop a validated indicator for estimating vaccine R&D funding across all US government agencies. Longer-term efforts may then build on this research to include vaccine R&D funding from non-US government funding sources (eg, pharmaceutical companies, private foundations). The NVAC also proposes to expand tracking of clinical-stage vaccines included in the NVPO report1 (indicator 2) to clinical phases beyond phase 1 and to include a broader range of priority pathogens than the 4 cited in the NVPO indicator. The WHO recently developed a vaccine pipeline tracker limited to clinical-stage vaccines aimed at protecting against HIV, malaria, TB, RSV, and enteric pathogens (eg, enterotoxigenic Escherichia coli, Shigella, and norovirus).65 The WHO intends to update the pipeline tracker every 6 months and expand beyond these vaccine targets. While the WHO pipeline tracker represents a tool that may work for tracking the progress of vaccine candidates against these targets, the United States could develop a similar clinical-stage pipeline tracker to include additional targets of national interest (Table 4). The NVAC recognizes, however, that developing an appropriate domestic indicator will likely require additional resources to define the specific inclusion and exclusion criteria, convene stakeholders to ensure consistent reporting and use of data, and extract and synthesize data into appropriate categories (eg, by pathogen or disease category, by stage of clinical development). In defining and validating the indicator, the NVPO may benefit from review of inclusion and exclusion criteria used for the WHO pipeline tracker or by commercial services that track product development (eg, PharmaProjects, BioMedTracker). Pipeline tracking should provide valuable information about the number of candidates entering clinical development and pressure points in the pipeline, at least in part by providing information about attrition rates at particular phases in development, but this depends on the data collection process.
Additional considerations for opportunity area 5
Although vaccine innovation discussions often focus on the development of new and improved vaccines (both for existing disease candidates and emerging pathogens), investments in innovation should include new platforms for the efficient presentation of antigens (eg, new vectors, nanoparticle technologies). The GVAP indicator to support the development of vaccine delivery technologies includes improvements to cold-chain equipment, vaccine thermostability, and delivery mechanisms (eg, nasal administration, vaccine patch technology). The NVAC recognizes innovation in these areas as critically important to facilitate access and efficient delivery of safe and effective vaccines.
Tracking the clinical-stage pipeline of vaccine candidates for some disease targets can occur with limited ongoing efforts due to the relatively slow pace of vaccine development and the availability of pipeline tracking data. However, establishing a consensus on a limited list of priority vaccine targets to track remains challenging. While the NVPO report1 supports the development of the Strategic Multi-Attribute Ranking Tool for Vaccines66 (SMART-Vaccines) to facilitate decision-making around prioritizing vaccine candidates, a formal list of priority targets endorsed across the federal government does not exist. In the absence of such a list, the NVAC proposes using existing prioritization lists to inform the selection of vaccine targets and to measure the robustness and diversity of the vaccine development pipeline. These existing lists may help to determine a finite number of targets that would satisfy the needs of several public health initiatives, both globally and domestically.
The WHO Product Development for Vaccines Advisory Committee recently published recommendations focusing on a list of 24 pathogens of high public health importance for which effective licensed vaccines do not currently exist.67 The pathogens included in this analysis represent targets with candidates previously identified as priority development targets by the GVAP9 and others, with the potential to substantially affect disease burden in low- and middle-income countries. Future activities by this committee will include focusing on targets that represent a significant unmet public health need and for which vaccines will probably show clinical proof-of-concept data within the next 3 years.67
The 2013 CDC report, Antibiotic-Resistant Threats in the United States, described antibiotic resistance as one of the most important threats to public health.68 While this report does not focus on vaccines or vaccine development, it categorizes antibiotic-resistant pathogens by threat level (ie, urgent, serious, concerning) according to factors such as clinical impact, economic impact, incidence, 10-year projection of incidence, transmissibility, availability of effective antibiotics, and barriers to prevention. Antibiotic-resistant bacteria classified as urgent threats represent immediate public health threats that require urgent and aggressive action.68
The National Institute of Allergy and Infectious Diseases provides a list of emerging infectious disease pathogens considered priority pathogens because of their recent emergence or their ability to rapidly spread in incidence or geographic area.69 Pathogens on this list include emerging infectious disease threats as well as pathogens potentially used as bioweapons. Their categorization depends on their threat to public health (and to national health security) and their ability to disseminate widely to the public.
The overlap of pathogens from each of the different prioritization lists was constructed based on the following inclusion criteria (Table 5):
All pathogens listed by the WHO Product Development for Vaccine Advisory Committee;
Priority pathogens in the CDC 2013 report, Antibiotic-Resistant Threats in the United States, especially pathogens classified as “urgent threats” (ie, those that present the highest level of threat);
Priority pathogens in the National Institute of Allergy and Infectious Diseases list of priority emerging infectious diseases; and
Pathogens already included in the WHO Pipeline tracking tool.
Table 5.
Clinical-stage priority vaccine candidates to track as part of the US National Vaccine Plan, 2015
| Pathogen | WHO Lista | CDC AMR Listb | NIAID Listc | WHO Pipeline Trackingd |
|---|---|---|---|---|
| Campylobacter jejuni | X | X | X | |
| Carbapenem-resistant Enterobacteriaceae | Urgent | X | ||
| Chikungunya virus | X | X | X | |
| Clostridium difficile | Urgent | X | ||
| Dengue | X | X | X | |
| Enterotoxigenic Escherichia coli | X | X | X | |
| Enterovirus 71 | X | X | ||
| Group B streptococcus | X | X | ||
| Herpes simplex virus | X | X | ||
| HIV-1 | X | X | X | |
| Malaria | X | X | ||
| MERS-CoV | X | X | X | |
| Neisseria gonorrhoeae | Urgent | |||
| Nipah virus | X | X | X | |
| Non-typhoidal salmonella disease | X | X | X | |
| Norovirus | X | X | ||
| Respiratory syncytial virus | X | X | ||
| Rift Valley fever virus | X | X | ||
| Shigella | X | X | X | X |
| Staphylococcus aureus | X | X | X | |
| Streptococcus pneumoniae | X | X | ||
| Tuberculosis | X | X | X | X |
| Universal influenza vaccine | X | X | ||
| Ebola virus | X | |||
| Zika virus | X |
Abbreviations: AMR, antimicrobial resistance; CDC, Centers for Disease Control and Prevention; HIV, human immunodeficiency virus; MERS-CoV, Middle East Respiratory Syndrome Coronavirus; NIAID, National Institute of Allergy and Infectious Diseases; WHO, World Health Organization.
aWHO Product Development for Vaccines Advisory Committee Target List.67
bCDC Antibiotic Resistance Threats Report, 2013.68
cNIAID Emerging Infectious Diseases/Pathogens.69
dWHO Pipeline Tracker.65
These potential target vaccine candidates represent just one example of how US government agencies may approach developing a list of target pathogens for the purpose of tracking candidates in the vaccine development pipeline.
Although the clinical-stage priority vaccine candidates identified provide some guidance (Table 5), the NVAC believes that further efforts should seek to develop tools and strategies to prioritize US government investments in innovation for (1) vaccines for established pathogens with no vaccines, (2) vaccines for emerging pathogens, and (3) improvements in existing vaccines. The indicators should also consider investments in vaccine delivery technologies. The NVPO plays an important role in convening stakeholders, and the NVAC encourages further efforts to support vaccine development prioritization decisions.
Conclusions and Recommendations
For the past 7 years, the 2010 National Vaccine Plan provided overarching strategic direction for a wide range of stakeholders collectively involved in the immunization enterprise, both in the United States and internationally. In this Mid-course Review, the NVAC carefully evaluated opportunity areas and defined priorities for strengthening our vaccine and immunization system based on progress made over the past half-decade and the changing immunization environment. The NVAC overall supports the NVPO report findings1 and its focus on the 5 priority opportunity areas but recommends that with the availability of additional funding or other resources, federal partners should continue to support the 2010 National Vaccine Plan7 objectives not included in the 5 opportunity areas described in this report. The NVAC also makes several additional recommendations.
The NVAC recommends giving strong consideration to previous NVAC reports to highlight recommendations for implementing the priorities outlined in the NVPO report,1 particularly the 2015 NVAC report, Assessing the State of Vaccine Confidence in the United States.2 The NVAC also recommends that its findings should inform the NVPO’s development of the 2020 National Vaccine Plan. While many of the activities described for these 5 opportunity areas lay the groundwork for improving our national and international immunization infrastructure, the NVAC suggests that real advances in these areas will take both near-term and longer-term strategies and resources to realize the full potential of these efforts. These strategies and resources must also be assessed within the context of new and existing population health care access disparities.
Although the 2010 National Vaccine Plan focuses on domestic priorities, Goal 5 seeks to “increase global prevention of death and disease through safe and effective vaccination.”7 The NVAC strongly supports the US commitment to global immunization efforts and acknowledges that strengthening immunization systems throughout the world will improve access to safe and effective vaccines and, ultimately, protect the US population from travel-related exposure and importation of vaccine-preventable diseases. For this reason, the NVAC recommends that the ASH continue to support and integrate global immunization efforts into the 5 opportunity areas highlighted in this review.
In the process of developing criteria for success within each opportunity area, the NVAC noted that some of the existing indicators lacked the detail, specificity, or flexibility to adequately measure progress or track emerging issues. In these cases, the NVAC recommends the development of other more appropriate indicators to better evaluate implementation of the National Vaccine Plan. While the NVAC appreciates that development of these new indicators lies beyond the scope, timeline, and resources of its review and the next few years, the NVAC urges the ASH to consider prioritizing the development of these new indicators in preparation for the next update of the National Vaccine Plan in 2020.
Finally, the NVAC recommends that the ASH take into account the additional considerations outlined in this report when informing decisions regarding resources and activities to fulfill the goals and objectives in the current National Vaccine Plan and to support the development of priorities for the next one. The confluence of emerging vaccine science and increasingly sophisticated data systems creates unprecedented opportunities for real-time disease surveillance and effective control of an ever-expanding portfolio of vaccine-preventable diseases. At the same time, we face growing challenges to vaccine access and confidence, both in the United States and abroad. Overcoming these challenges and building efficient systems for the development and delivery of new or improved vaccines must receive the highest public health priority. The NVAC hopes that this report will serve as a useful tool in refining our collective strategies for shaping the future of the US immunization enterprise, both domestic and global.
In summary, the NVAC recommends the following:
The ASH should charge the NVPO, in coordination with relevant departments and agencies, to adopt existing indicators (eg, HP2020 indicators) to track progress on the National Vaccine Plan goals and to prepare an annual report to the ASH and the NVAC on progress.
The ASH should charge the NVPO, in coordination with relevant departments and agencies, to develop and validate new indicators within each of the 5 opportunity areas to ensure improved tracking of goals. The new indicators should include one that will track and report on US government annual financial investments in vaccine innovation that support the development of (1) vaccines for established pathogens that have no vaccines, (2) vaccines for emerging pathogens, and (3) improvements in existing vaccines. The new indicators should also consider investments in vaccine delivery technologies.
The ASH should continue to strongly support US contributions to global immunization efforts and the integration of global immunization efforts into the opportunity areas as appropriate.
The NVPO should continue to implement the recommendations from previous NVAC reports, such as the 2015 NVAC report Assessing the State of Vaccine Confidence in the United States. By doing so, the NVPO can highlight NVAC recommendations related to implementing the priorities outlined in the NVPO 2010 Mid-course Review. The NVPO should use the framework defined in this report to make further advances under the existing 2010 National Vaccine Plan for both domestic and global immunization outcomes.
The ASH should charge the NVPO to develop the 2020 National Vaccine Plan, which should incorporate the findings in this report and consider the impact of health care disparities on implementation and achievement of the objectives of the 2020 Plan.
The ASH should charge the NVPO, in coordination with relevant departments and agencies, to begin developing strategies to (1) identify priorities for US government investments in vaccine-related innovations and (2) overcome barriers that inhibit innovation.
Acknowledgments
The members of the National Vaccine Advisory Committee (NVAC) Mid-course Review Working Group recognize many contributions that improved this report. We appreciate the efforts of Jennifer Gordon and Anju Abraham for their administrative oversight in facilitating Working Group meetings, assisting with report drafts and the review process, and providing overall staff support. We thank Dr Bruce Gellin of the National Vaccine Program Office for offering valuable insights while providing complete independence of our work. We thank Karen Ernst, Ruth Lynfield, Judith Mendel, and Cindy Pellegrini for sharing their research findings and subject matter expertise in presentations to the Working Group. We thank Kathryn Edwards, Maureen Hess, Rhonda Kropp, Nancy Messonnier, Kristin Pope, and members of the NVAC for providing comments on an earlier draft. Finally, we thank the individuals and organizations that participated in the stakeholder engagement process as part of the NVPO review, and we thank the American Academy of Family Physicians, PATH, and Walgreens for submitting feedback during the public comment period.
Footnotes
Declaration of Conflicting Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding: The authors received no financial support for the research, authorship, and/or publication of this article.
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