Indirect Effects in Health Economic Models of Vaccines: Should We IncludeThem, and How Do We Model Them?

POSA254 An Initial Framework to Describe and Classify Integrated Scientific Advice Procedures for Vaccines

ObjectivesPneumococcal vaccine recommendations have become increasingly complex. Thisstudy aims to understand how national immunization technical advisory groups(NITAGs) and health technology assessment (HTA) agencies of 5 Europeancountries and the United States formed their pneumococcal vaccinerecommendations, by providing reviewed evidence and key drivers for newrecommendations.MethodsCenters for Disease Control and Prevention, European Centre for DiseasePrevention and Control, and National Health Authorities Web sites werescreened to capture the evolution of pneumococcal recommendations. Anarrative review was conducted on NITAGs and HTA bodies’ Web sites.Assessments of pneumococcal vaccines published from 2009 to 2022 wereincluded.ResultsThirty-four records were identified including 21 assessments for risk groups,17 for elderly, and 12 for children. Burden of disease and vaccinecharacteristics were almost systematically reviewed during assessments. All6 countries recommended the use of higher-valent pneumococcal vaccine (PCV;i.e., PCV10 and PCV13) in childhood vaccination programs, given theirbroader serotype coverage and their comparable profile to PCV7. PCV13 wasprogressively added to the vaccine schedule (in addition to polysaccharidevaccine) in at least the high-risk group, given the high burden in thispopulation and expected additional benefits of PCV13. For the elderly,unlike the United States, European countries issued negative recommendationfor PCV13 routine use because of substantial herd effects from childhoodvaccination program making PCV13 likely not cost-effective.ConclusionsThis research provides an overview of decision-making processes forhigher-valent PCVs recommendations and could be of interest to anticipatethe place of next generation of PCVs in the vaccination landscape.HighlightsBy describing evidence-based criteria for decision making, this studyemphasizes the framework analysis of NITAGs and HTA bodies whenassessing pneumococcal vaccines and demonstrates that variationexists between countries and also according to populationevaluated.While the burden of disease and immunogenicity/efficacy data werealmost systematically reviewed by national stakeholders, economicassessments were reported to a lesser extent but played a major rolein the limited use of PCV13 in the adult population.

Issue/problemThe WHO has recommended for many years to adopt transparent and standardized methods to decide upon the introduction of vaccines at national level. For this purpose, the Global Vaccine Action Plan has envisaged the establishment of National Immunization Technical Advisory Groups (NITAGs) to issue independent advice relied on the assessment of vaccines efficacy and safety and health technology assessment (HTA).Description of the problemSo far, 172 countries worldwide have a NITAG. Despite the growth in the number of NITAGs worldwide and their strengthening following process indicators identified by the WHO, the way how NITAGs issue recommendations and how they are considered in the development of vaccine policy still represent a matter to the attention of the scientific and policy community.ResultsThe evidence shows that assessment frameworks vary across countries. Furthermore, the legal basis and the authority, namely binding or advisory, recognised to them could influence the way how NITAGs work and impact on vaccine policy. Eventually, the final decision is also led by other aspects, including financial and contextual factors that are less standardizable but should be always taken into consideration in health policy. In fact, the final decision on the inclusion of a vaccination into the national immunization program is made by the Ministry of Health also based on the evaluation of HTA bodies working in the country.LessonsConsidering the central role of NITAGs in vaccine policy, some efforts should be done in order to make NITAGs more authoritative and collaborative. This could help, from one side, to make the relationship between final decision and NITAGs recommendations clearer and, on other one, to make it possible to have shared and timely evaluations. In this respect, Joint Clinical Assessment envisaged by the new EU regulation on HTA could prepare the way for a more transparent and timely vaccine policy at European level.

IntroductionStarting from 2030, vaccines in the European Union (EU) require joint clinical assessments (JCAs), and joint scientific consultations (JSCs) can be requested from 2025. Involvement of national immunization technical advisory groups (NITAGs) is crucial to address vaccine specificities. However, NITAGs are currently not considered in the EU health technology assessment (HTA) framework. This study highlights potential risks for non-applicability of vaccine JCA reports nationally.MethodsThis study examined where in the JCA and JSC implementation process NITAGs could play an important role and highlighted the practical challenges of incorporating vaccine JCA reports into already very heterogeneous and complex vaccine access pathways across EU Member States. The EU HTA Regulation process was tested for three countries with different vaccine market access characteristics. This study was conducted using JCA guidance documents, NITAG vaccine assessment guidelines, and communications with the respective decision-making bodies.ResultsThe EU HTA Regulation framework requires adjustments for vaccine-specific considerations. NITAGs across the EU vary in experience, resources, expertise, and influence on decision-making regarding vaccine assessment and inclusion in the national immunization program. In addition to JCA and JSC, the EU HTA framework also covers horizon scanning, which several NITAGs are currently involved with at national level.. However, the EU HTA framework currently lacks explicit requirements for NITAG input in horizon scanning, JSC, and JCA processes. This could lead to unnecessary duplication of work, further complexity of the processes, and lengthening of population time to access to new vaccines.ConclusionsThe EU HTA framework of vaccines aims to avoid duplicate efforts and enhance patient access, but current processes that will be introduced may not achieve this optimally. Early and systematic inclusion of NITAGs in the horizon scanning, JSC, and JCA processes is pivotal to mitigate the risk of non-applicability and to successfully realize the objectives of the EU HTA framework.

Given their crucial role in vaccine assessment, National Immunization Technical Advisory Groups (NITAGs) should be considered in the Regulation on Health Technology Assessment (EU HTAR) to maximize the benefits of the EU HTAR for vaccines. This review and perspective piece identifies the gaps arising from NITAGs potential lack of involvement and proposes strategies for involving them. A targeted literature and guideline review was conducted to evaluate NITAGs' current and future role in relation to the EU HTAR. The impact of the EU HTAR on diverse national HTA frameworks was explored in a three-country case study. Recommendations were developed to leverage strengths and address weaknesses to ensure consistent and cohesive vaccine assessments. The case study revealed potential overlaps between NITAGs and the EU HTAR, particularly regarding horizon scanning and joint scientific consultations. The involvement of NITAGs in national assessments varies, influencing how well joint clinical assessment reports will ultimately align with and be applicable to individual Member States. Stronger consideration of vaccines within the EU HTAR and NITAG involvement can streamline assessments, reduce duplication, and improve alignment between European and national processes. Strategic actions, including capacity building and collaborations between NITAGs, are key in facilitating this process.

Supporting National Immunization Technical Advisory Groups (NITAGs) in development of evidence-based vaccine recommendations and NITAG assessments – New tools and approaches

PNS76 A PAN-EUROPEAN HTA, A SINGLE US PAYER?

In July2024, Health Canada authorized a 21-valent pneumococcal conjugate vaccine (Pneu-C-21) for use in adults. To conduct a systematic review of the cost-effectiveness of Pneu-C-21 for preventing pneumococcal disease in adults. We conducted a systematic search of the literature and National Immunization Technical Advisory Groups' websites on July3, 2024. We included economic evaluations that assessed Pneu-C-21 as a vaccination strategy among adults aged 18years and older. Costs were adjusted to 2023Canadian dollars. We identified 10studies in our search, five of which were summarized in our review. No economic evaluations were conducted in Canada. All economic evaluations used static cohort models and incorporated indirect effects from paediatric pneumococcal conjugate vaccination in primary or sensitivity analyses. Although incremental cost-effectiveness ratios were heterogeneous across included economic evaluations, overall, they qualitatively identified the same vaccination strategies as optimal within the given age and risk groups. Pneu-C-21 is likely to be cost-effective in adults aged 65years and older and adults under the age of 65years with specific high risk conditions. Pneu-C-21 is likely to be cost-effective in adults within specific age and risk groups. The applicability of the included economic evaluations to adults living in Canada is limited because the serotype-specific incidence of pneumococcal disease and the impact of indirect effects from pediatric vaccination varies by region and over time.

In many countries, national vaccination recommendations are developed by independent expert committees, so-called national immunisation technical advisory groups (NITAG). Since the evaluation of vaccines is complex and resource-demanding, collaboration between NITAGs that evaluate the same vaccines could be beneficial. We conducted a cross-sectional survey among 30 European countries in February 2014, to explore basic characteristics and current practices of European NITAGs and identify potential modes and barriers for collaboration. Of 28 responding countries, 26 reported to have a NITAG or an equivalent expert group. Of these, 20 apply a systematic approach in the vaccine decision-making process, e.g. by considering criteria such as country-specific disease epidemiology, vaccine efficacy/effectiveness/safety, health economics, programme implementation/logistics or country-specific values/preferences. However, applied frameworks and extent of evidence review differ widely. The use of systematic reviews is required for 15 of 26 NITAGs, while results from transmission modelling and health economic evaluations are routinely considered by 18 and 20 of 26 NITAGs, respectively. Twenty-five countries saw potential for NITAG-collaboration, but most often named structural concerns, e.g. different NITAG structures or countries’ healthcare systems. Our survey gathered information that can serve as an inventory on European NITAGs, allowing further exploration of options and structures for NITAG collaboration.

National Advisory Groups and their role in immunization policy-making processes in European countries

PNS68 Latin America HTA: Brazil and Argentina Report Card

BackgroundVaccine market access (VMA) pathways across the European Union (EU) and the United Kingdom (UK) are complex, lengthy, and heterogeneous, particularly when compared with pharmaceuticals. The knowledge base to inform recommendations for optimization of VMA is lacking. We therefore conducted a comprehensive evaluation of EU VMA pathways. MethodsResearch in two phases included: (1) mapping VMA pathways in each EU member state (including the UK) based on a literature review, expert interviews, and mathematical archetyping; and (2) interviews with vaccine experts to identify barriers, drivers, and recommendations for regional VMA alignments. ResultsKey steps in VMA across the EU include horizon scanning, early advice, National Immunization Technical Advisory Group (NITAG) recommendation for inclusion in national immunization programs, health technology assessment (HTA), final decision and procurement. We found significant complexity and heterogeneity, particularly for early advice, and in the roles, decision-making criteria, and transparency of NITAGs and HTA bodies. The most important drivers for rapid VMA included demonstration of disease burden and vaccine benefit (e.g., efficacy, safety, economic). Key barriers were budget limitations and complexity/clarity of VMA processes (e.g., need for national-regional consensus, clarity on process initiation, and clarity on the role of HTA). Recommendations for alignment at EU and member-state levels include information sharing, joint clinical assessment, initiatives to address funding and political barriers, and improved transparency by decision-making bodies. Early engagement with vaccine stakeholders was a key recommendation for manufacturers. ConclusionsThere is significant potential for alignment, collaboration, and improvement of VMA across the EU. Roles, responsibilities, and transparency of key bodies can be clarified. The COVID-19 pandemic response should stimulate policies to improve access to all vaccines, including routine ones, and form the foundation upon which a consistent vaccine ecosystem can be created for the EU, one that is resilient, consistent between member states, and fit for purpose.

INTRODUCTION:Historically, many Health Technology Assessment (HTA) bodies were developed with a focus on addressing rapidly rising drug costs and the unique need to evaluate each drug as a de novo entity. The degree to which the unique needs for evaluating technologies vis a vis drugs are reflected in distinct HTA methods and activity is to date understudied.METHODS:We examined HTA's reviews of two technologies: WATCHMAN™, a device to reduce the risk of stroke in certain patients and Alair™, a procedure-based treatment for severe asthma. Both technologies have been extensively reviewed by HTA bodies and payers in many countries. These HTA reviews are compared to a convenience sample of these HTA's bodies reviews of drugs and qualitative differentiators between these two categories explored.RESULTS:The differences and similarities (for example, in rigor and necessity of evidence) between US Section 510(k) clearances, US premarket approval (PMA), and US new drug application (NDA) regulatory pathways have not been clearly understood by HTA or reflected in their methodologies employed. Additionally, emergent methodologies such as Bayesian statistical analyses may encounter challenges within technologies reviews. HTA bodies may not be cognizant of development timelines or the timelines of comparators. Finally, HTA bodies may overestimate device adoption rates.CONCLUSIONS:The differences in evidence requirements for regulatory approval between US 510(k), US PMA, and US NDA pathways have not been reflected in different methodological approaches within HTA bodies reviews. Opportunities and novel methods are needed for HTA bodies to derive imputed comparisons between technologies that may have inherently incongruent timelines. Finally, HTA bodies could benefit from methods to more accurately estimate projected adoption curves. Challenges exist using frameworks, paradigms, and methodologies initially established for, and commonly used for, pharmaceuticals on device evaluations; leaders of HTA methods can improve the situation by providing guidance and recommendations for more appropriate HTA methods to evaluate devices.

IntroductionCanada’s National Advisory Committee on Immunization (NACI) makes recommendations on the use of human vaccines. Provinces and territories subsequently use the advice to make decisions on public funding and program implementation. Traditionally, NACI reviewed vaccine characteristics and burden of illness.With its recent expanded mandate, NACI now considers cost-effectiveness via economic evaluations, among other decision determinants. As such, new processes and guidelines were needed to formalize the incorporation of economic evidence into federal vaccine decision-making.MethodsTwo task groups were convened respectively to develop NACI’s “Economic Process” and “Guidelines for the Economic Evaluation of Vaccination Programs in Canada”. The groups conducted environmental scans to inform their work, as well as engaged with government partners, decision-makers, academics, national immunization technical advisory groups from other countries, health technology assessment agencies, industry, patient groups, among others.ResultsThe Economic Process outlines when and how NACI incorporates economic evidence for vaccine recommendation. For instance, it describes how policy questions are prioritized given institutional capacity constraints for generating economic evidence. It also describes how policy questions are assessed to determine the appropriate type of economic evidence required (i.e., systematic review, economic evaluation, multi-model comparison of external models).The Economic Guidelines provide recommendations in 15 chapters on how to conduct economic evaluations (i.e., from defining the decision problem to reporting). Unlike other health technologies, vaccines have the potential to affect both vaccinated and unvaccinated individuals. Hence, the Guidelines consider population-level impacts such as externalities (e.g., herd immunity, age-shifting of disease) and spillover effects. They also discuss equity considerations and non-health impacts of vaccines such as to productivity, consumption and education.ConclusionsThe Economic Process and Economic Guidelines promote the generation and use of credible and standardized economic evidence. They advocate for transparency, allowing evidence to be used across jurisdictions beyond Canada. Next steps include documentation of user feedback, incorporation of Indigenous considerations, and formal evaluations.

The EU Health Technology Assessment Regulation (HTAR) introduces joint clinical assessments (JCAs) to harmonize clinical evidence evaluation across Member States. JCAs are commencing in 2026 for high-risk medical devices (MD) and in vitro diagnostics (IVD), but little is known about how national health technology assessment (HTA) bodies are preparing for implementation. This study aims to explore how selected European Union (EU)/European Economic Area HTA bodies are planning for JCAs integration and HTAR implementation for high-risk MD/IVD. Semistructured interviews were conducted with 15 participants from 11 different HTA bodies across 11 EU/European Economic Area Member States. Interviews were recorded and transcribed verbatim before being anonymized and coded using NVivo Software. Data were analyzed using thematic analysis. All participants recognized JCAs as a potential tool for improving evidence quality for high-risk devices and highlighted their willingness to use JCA-generated evidence in their clinical assessment. Some HTA bodies have initiated procedural or legislative adaptations; however, many remain in an observational position, waiting for further implementation documents. Key opportunities identified included work sharing, improved evidence standards, and capacity building, particularly in smaller HTA systems that might not have access to high-quality assessments without JCAs. However, substantial challenges were reported, including regulatory uncertainty, timing misalignments, and limited manufacturer preparedness for JCA evidence demands. HTAR is viewed as an opportunity to strengthen HTA practices for high-risk MD/IVD. However, realizing its goals will require further collaboration, alignment of procedural timelines, and investment in national capacity. Further studies are needed after full HTAR implementation for high-risk MD/IVD to capture ongoing experiences.