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Article

Health Technology Assessment of Vaccines in Italy: History and Review of Applications

by
Sara Boccalini
1,*,
Rosalia Ragusa
2,
Donatella Panatto
3,4,
Giovanna Elisa Calabrò
5,
Paolo Angelo Cortesi
6,
Gabriele Giorgianni
7,
Carlo Favaretti
8,
Paolo Bonanni
1,
Walter Ricciardi
5 and
Chiara de Waure
9
1
Department of Health Sciences, University of Florence, 50134 Florence, Italy
2
HTA Committee, Azienda Ospedaliero Universitaria Policlinico “G. Rodolico-San Marco”, 95123 Catania, Italy
3
Department of Health Sciences (DISSAL), University of Genoa, 16132 Genoa, Italy
4
Interuniversity Research Centre on Influenza and Other Transmissible Infections (CIRI-IT), 16132 Genoa, Italy
5
Section of Hygiene, Department of Life Sciences and Public Health, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
6
Research Centre on Public Health (CESP), University of Milano-Bicocca, 20132 Monza, Italy
7
UOS Coordinamento Operativo delle Attività Vaccinali Metropolitane e Provinciali–ASP 3 Catania, 95128 Catania, Italy
8
Centre on Leadership in Medicine, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
9
Department of Medicine and Surgery, University of Perugia, 06123 Perugia, Italy
*
Author to whom correspondence should be addressed.
Vaccines 2024, 12(10), 1090; https://doi.org/10.3390/vaccines12101090
Submission received: 9 August 2024 / Revised: 20 September 2024 / Accepted: 23 September 2024 / Published: 24 September 2024
(This article belongs to the Special Issue Vaccination and Public Health in the 21st Century)
Versions Notes

Abstract

:
Background/Objectives. Many vaccines have been developed in recent decades, and many more will be available in the future. When new safe and effective vaccines are available, decision-makers must extensively assess them before including them in the national immunization plan and issuing recommendations. The Health Technology Assessment (HTA) could be an objective, transparent, and comprehensive approach to guiding the decision-making process for the use of vaccines. Objectives and Methods. The aim of this study was to review the indications for HTA use contained in Italian institutional documents on vaccination, namely the National Immunization Plans (NIPs) and available full Italian HTA reports on vaccines, assessing their availability at the time of national recommendations’ introductions. Results. HTA has been recognised as an eligible approach to deciding upon the introduction of vaccines through the NIPs of 2012–2014 and 2017–2019, and the last NIP, of 2023–2025, highlights the lack of funding dedicated to the production of independent HTA reports that can be used for issuing recommendations. In 2007–2023, twenty full HTA reports on vaccines were published in Italy: eight reports on influenza vaccines, five on Human Papilloma Virus (HPV), three each on meningococcal and pneumococcal vaccines, and one on rotavirus vaccine. HTA was applied with different purposes, namely the evaluation of new vaccines or their re-assessment, but it was not always timely with respect to both the marketing authorisation and the issuing of national recommendations for use. Conclusions. As HTA can be considered the best tool to disentangle the overall value of vaccines, it would be desirable for it to be used more and more to provide the evidence for efficient resource use. This calls for action to improve the transfer of HTA results to decision-makers, to try to fill the gap between research and decision and foster evidence-based recommendations.

1. Introduction

Vaccines are the health intervention with the most effect on mortality reduction and population growth, after safe water [1,2,3,4,5,6,7,8,9]. Many vaccines have developed in recent decades, and many more will be available in the future [10,11,12,13,14,15]. When new safe and effective vaccines are available, decision-makers must extensively assess them before issuing recommendations on their inclusion in national or regional immunization plans.
There are four basic values considered in the assessment of vaccines and in the subsequent decision-making process behind the issuing of recommendations. These core values are the incidence of the vaccine-preventable disease, its lethality, its severity, and the cost-effectiveness of vaccination [16,17]. However, other issues, such as the impact on non-health outcomes, societal impact, and pragmatic issues should be considered in the decision-making process, as suggested by the World Health Organization [18,19,20].
An objective, transparent, and comprehensive approach that is useful for addressing all these issues and supports the National Immunization Advisory Group (NITAG) is the Health Technology Assessment (HTA). HTA is a systematic and multidisciplinary evaluation of health technologies that addresses the potential direct and indirect consequences of their use. It aims to determine the value of a health technology and to inform how it can be used in the best way in health systems. HTA relies on the collection and synthesis of evidence regarding the medical–clinical, social, organisational, economic, ethical, and legal implications of a health technology, evaluating multiple dimensions such as efficacy/effectiveness, safety, cost, and social–organisational impact. Therefore, HTA can be used to support the decision-making process in health care by providing evidence about given technologies [21,22,23,24,25,26].
HTA has reached a juncture where relevant and impactful changes for European citizens are expected. The HTA Regulation 2021/2282 [27] will apply as of January 2025 and will call for a harmonized HTA among member states to improve access to health technologies. Vaccines will adhere to this HTA Regulation starting from 2030. Actually, a deep heterogeneity in the assessment of vaccines is emerging among NITAGs [28,29]. In Italy, the NITAG was established only recently and did not immediately reach the target of becoming a reference point for Italian vaccination policies [30]. Nevertheless, a long-lasting history regarding HTAs of vaccines is in place in Italy, with the first HTA report being published 10 years ahead of the establishment of the NITAG. The inclusion of a vaccine in the Italian National Immunization Plan (NIP) is decided by the Ministry of Health, as in other European countries, representing a critical step for Italy due to the need for unanimous regional consensus [31]. To date, the interlinkages between HTAs and vaccination recommendations issued at a national level have not been extensively addressed in the literature. Several works have focused on aspects used by NITAGs or HTA bodies to issue recommendations on specific vaccines, providing a more methodological view of the topic [32,33,34]. In this light, studies in countries from which information on HTAs of health technologies other than medicines is less common are appropriate [35]. As a matter of fact, HTAs on vaccines are uncommon relative to clinical interventions or other public health activities [36].
The aim of this study was to evaluate the use of HTA in the landscape of vaccines in Italy though an overview of the official indications provided by vaccine-relevant Italian institutional documents and of the available full Italian HTA reports on vaccines, assessing their availability at the time of national recommendations’ introductions.

2. Materials and Methods

The study was performed in two steps. In the first phase we retrieved official indications for the use of HTA in the vaccine-related decision-making process. Therefore, we collected vaccine-relevant institutional documents, namely Italian NIPs, and searched for “HTA” or “Health Technology Assessment” or “valutazione delle tecnologie sanitarie” to extract any information on the use of HTA. In the presentation of the results, we described whether HTA was reported as an evaluation approach for the assessment of vaccines, and we reported any change in this topic that occurred over time. NIPs were chosen because they are national programmes addressing vaccine-preventable disease control that are issued by the Italian Ministry of Health, which is the main institution responsible for public health at the national level. All the available NIPs from 2000 to June 2024 were considered for this study. The year 2000 was chosen as the 1999 reform of the Italian National Health Service reaffirmed the central role of the government in setting the national health policy agenda [37]. In the second phase we systematically searched and collected full HTA reports on vaccines published in Italy from 2000 to the present. Particularly, a hand search was performed on the websites of two journals (Italian Journal of Public Health and Journal of Preventive Medicine and Hygiene) using a combination of keywords including “HTA”, “Health Technology Assessment”, “valutazione delle tecnologie sanitarie”, “vaccino”, “vaccinazione” [38,39]. These two journals were selected as they are committed to publishing full HTA reports on vaccines in Italy. The hand search of these two journals was also considered a reasonable approach because national HTA reports are published in Italian, and the two journals allow the publication of single-issue supplements in Italian. The hand search was performed by one researcher and the results were validated through consultation with all of the working group. HTA reports were considered eligible if they were full reports that described the characteristics and current use of the technology, its safety and efficacy, and its cost-effectiveness, and if they provided information on its costs/financial impact and organisational aspects [40]. The collected HTA reports were grouped together according to the vaccine-preventable disease. The examined vaccine types and target population/vaccination strategy were evaluated following a chronological order. In addition, the year of publication of the reports was related with the year of vaccine marketing authorization issued by the Italian Medicines Agency (Agenzia Italiana del Farmaco—AIFA) and the national recommendation included in the NIPs.

3. Results

3.1. Indications for Using HTA Based on Institutional Documents in Italy

In Italy four NIPs were issued from 2000 to the present: NIP 2005–2007 [41], NIP 2012–2014 [42], NIP 2017–2019 [43], and the current NIP, NIP 2023–2025 [44]. The NIP of 2012–2014 is the first institutional document on vaccinations where HTA is cited as an evaluation approach for the inclusion of vaccines in the NIP. As a matter of fact, this plan highlights the increasing number of vaccines over time and, consequently, the need to make rational use of the limited resources available to maximise the population’s health. To do this, “clear, robust and shared criteria” to support decision-making processes regarding the introduction of vaccines are needed. The HTA was, therefore, recognised as the approach that best meets these evaluation needs [42].
HTA has been confirmed as the most correct and transparent approach to supporting health decision-making by the NIP of 2017–2019. In this document it is also stressed that HTA is important and necessary because vaccinations are a public health intervention carried out on healthy people with intangible benefits that are not always adequately perceived (absence of disease and reductions in health care as well as the direct and indirect costs of the disease). In the assessment, therefore, beyond the costs of vaccines and vaccination, the short-, medium, and long-term benefits should be considered [43].
The current NIP of 2023–2025 specifies that the availability of new vaccines or new indications for existing and used vaccines represents an additional opportunity for the protection of the individual and also of the community. However, the introduction of new vaccines and the implementation of new vaccination strategies may be problematic due to the increased financial commitment (purchase of new vaccines or additional doses of existing vaccines, staff training, communication and dispersing information to the population, etc.) and the impact on the organisational system. The decision-making process leading to the introduction or implementation of a vaccine must, therefore, weigh up many aspects. These aspects may slow down or hinder the inclusion of vaccines in the national recommendations [44].
In addition, the NIP of 2023–2025 highlights the lack of a standardized decision-making process for the inclusion of vaccines in national recommendations and of funding dedicated to the production of independent cost-effectiveness analyses and HTA reports that can be used to issue recommendations by the NITAG and the Ministry of Health [44].

3.2. HTA Reports on Vaccines Published in Italy

The first full HTA report on a vaccine was published in Italy in 2007 [45]. In the time period considered, twenty full HTA reports on vaccines were published either in the Italian Journal of Public Health or in the Journal of Preventive Medicine and Hygiene: eight (40%) reports referred to influenza vaccines, five (25%) to HPV, three each (15%) to meningococcal and pneumococcal vaccines, and one to the rotavirus vaccine (5%). In Table 1 the full HTA reports are reported according to the type of vaccine [45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64].
In Italy, the HTA approach was first applied to assess the new HPV vaccines. As a matter of fact, the tetravalent HPV vaccine (HPV4) was authorized by the AIFA in 2006 [65] while the bivalent HPV vaccine (HPV2) was authorized in 2007 [66]. The HTA report on HPV2 was published in 2007 [45], while the one on HPV4 was published in 2009 [46]. These reports aimed to assess the use of the new and expensive vaccines against cervical cancer. The national HPV vaccination campaign targeting females in their twelfth year of age started in 2007/2008 based on the agreement between the Ministry of Health and the Italian regions and autonomous provinces (Intesa Stato-Regioni del 20 dicembre 2007), and the recommendation on HPV vaccination for female adolescents was then included in the NIP of 2012–2014 [42]. In 2014 the HTA approach was applied to re-assess the HPV vaccination 5 years after its introduction and to evaluate the two-dose schedule [47]. In 2015 the new 9-valent HPV vaccine was authorized in Italy [67] and in 2017 this new vaccine was assessed in an HTA report [48]. In 2019 an HTA report was performed to evaluate the use of the HPV9 vaccine in women treated for HPV-related diseases based on the availability of new evidence on the efficacy of vaccination in this risk group [49]. Nevertheless, this strategy was included only in the NIP of 2023–2025, even though it should be taken into consideration that in 2020 an official guideline on post-treatment vaccination was published [68].
The pneumococcal vaccination was another instance where HTA was applied to assess both new vaccines and their new indications for use in other target groups. The 13-valent conjugated pneumococcal vaccine (PCV13) was authorized by the AIFA for use in the paediatric population in December 2009 [69] and the first HTA report was published in 2010 [50]. Subsequently, based on new evidence, the vaccine was also approved for use in the adult population and a new HTA was published in 2013 [51]. Another conjugate vaccine, namely the 15-valent pneumococcal vaccine (PCV15), was authorized for use in people aged 18 years or older in 2021, and then approved for use in the paediatric population in 2022 [70]. In regard to this vaccine, an HTA report focused on the paediatric population was available one year later, after the marketing authorization [52]. Eventually, the 20-valent pneumococcal vaccine (PCV20) received authorization for use in people aged 18 years or older in 2022, with extension to the paediatric population in the last year [71], but no HTA reports are available yet. In respect to the preferential use of one vaccine over the other, it should be observed that only in the NIP of 2017–2019 we found a reference to administer the vaccine with the greater protection against circulant pneumococcal serotypes in the paediatric population [43]. The last NIP did not specify the type of conjugate vaccine that should be preferably used either in paediatric or in adult and elderly populations [44].
HTA in Italy has a broader application in the field of influenza vaccines. Five HTA reports [53,54,56,58,59] have been performed on different influenza vaccines (quadrivalent egg-based vaccine, adjuvanted vaccine, cellular-based vaccine, live attenuated vaccine, high-dose vaccine). Two reports [57,60] were reassessments of vaccines already evaluated that were conducted based on new indications/formulations. Lastly, a report [55] assessed the introduction of a paediatric vaccination strategy against influenza. All these reports were published from 2015 to 2023. The publication years of the HTA reports are close to the first influenza season in which each vaccine or its new indication were available, except for the adjuvanted trivalent vaccines, which have been used since 1997/1998 and were evaluated through HTA only in 2017 (Table 2).
Rotavirus vaccines were authorized by the AIFA in 2006 [72,73]; however, in this case, the HTA of the live attenuated vaccine was performed only in 2014 [61] and it took about ten years from marketing authorization to the introduction of rotavirus vaccination into the NIP of 2017–2019 [43] (even though many Italian regions had already adopted rotavirus vaccination at that time).
Concerning meningococcal vaccines, the quadrivalent meningococcal B vaccine for newborns was authorized in 2013 [74] and in the same year a specific HTA report was already available [62]. The recommendation for this vaccine was then included in the NIP of 2017–2019 [43], even though some Italian regions had already started to administer it at that time. The bivalent meningococcal B vaccine for adolescents had a different market access pathway: it had marketing authorization in 2017 [75] and an HTA was available in 2019 [63], but to date, there is still not a national recommendation to use it, although, based on the regional autonomy, some regions have started providing the vaccination free of charge. Concerning meningococcal C immunization, this vaccination has been recommended at 13–15 months of life and in adolescents from the 2012–2014 NIP onwards [42]. According to the increasing evidence of protection from meningococcal vaccination waning over time [76,77], and based on the availability of a quadrivalent meningococcal vaccine, a four-cohort strategy (immunization at 13–15 months, 6 years, 11 years, and 19 years of age) with a quadrivalent meningococcal vaccine was assessed in 2021 [64], but this multiple preventive intervention is not included in current recommendations.

4. Discussion

The aim of this study was to make an overview of the indications for the use of HTA in the vaccine-related decision-making process, as well as its actual application in Italy. The findings of our work are relevant to understanding how far the evidence supports the decisions on vaccination at the Italian level. The results are also of interest considering the growing attention to evaluating the functionality, but also the output, of NITAGs worldwide [78]. The results of the work highlight that the HTA approach has been recognized as an invaluable approach to guiding the vaccine-related decision-making process for more than 10 years in Italy. Nevertheless, the actual use of HTA in decision-making shows room for improvement. This could also be due to the history of the Italian NITAG that was established in 2017, dissolved, and then established again in its current composition in 2021 [30]. As a matter of fact, HTA reports on vaccines published in Italy were developed by academic research groups with companies’ unconditional grants, and this could have prevented their timely consideration in the development of recommendations [30]
Delving into specific diseases, we observed that, not surprisingly, HTA was first applied to HPV vaccines, which are very expensive preventive interventions with a great potential to control cancers. In respect to HPV vaccines, HTA was also adopted to reassess the impact of these vaccinations some years after their introduction and in light of new indications. These reassessment exercises are quite relevant to monitoring vaccination policies and for continuous quality improvement. A reassessment exercise was also observed with respect to pneumococcal conjugate vaccines, namely PCV13, based on new indications. As far as pneumococcal vaccines are concerned, one of the last new products, PCV15, was assessed through HTA, although national recommendations were not still impacted by the results of the report. The available HTA reports also belatedly or partially impacted NIPs with respect to rotavirus and meningococcal vaccinations. As a matter of fact, the HTA report on the rotavirus vaccine was performed many years after the marketing authorization and the immunization was included in the NIP. This delay in the introduction of rotavirus vaccination into the NIP could be also attributable to the low perception of the health problem and of its societal impact [79,80,81,82,83,84]. For meningococcal vaccines, the HTA reports are relevant to fully understanding the real impact of infection and immunization in Italy. In fact, in this case, the collection of scientific evidence highlights that, even if the infection has a very low incidence [85,86,87,88,89,90,91], the health impact (complications, short- and long-term sequelae, and deaths) is very significant [62,63,64,92,93,94,95,96,97]. This aspect is relevant in the decision-making process, even though it is not always sufficient to include the different vaccines and vaccination strategies in the national recommendations, probably due to economic issues.
Our findings show that, in Italy, HTA has been applied widely for influenza vaccination. This is related to the many types of vaccines available in recent years, each with specific characteristics. The different HTA reports have made it possible to understand that influenza vaccines are not similar; therefore, they must be administered according to appropriateness criteria [98]. All the HTA reports show that influenza vaccination, with any vaccine, is essential for avoiding complications, hospitalizations, and deaths, but that vaccination with the most suitable product for each type of subject could optimize health outcomes at a very modest additional cost. This kind of information is relevant when pursuing a value-based approach to vaccination and when issuing specific recommendations [99].
Overall, our findings suggest that in Italy decision-makers have not been using HTA to its full potential and this has also been reported in the NIP of 2017–2019 [43].
Potential reasons behind the non-use of HTA reports in Italy could be that they are not delivered by an independent national organization and that there is not a comprehensive and targeted dissemination strategy for their results. As a matter of fact, while in the NIPs of 2012–2014 [42] and 2017–2019 [43] HTA is recognised as the primary assessment approach for the introduction of new vaccines, the current NIP of 2023–2025 [44] highlights the gap in funding dedicated to the production of independent HTAs that can be used for developing vaccination recommendations by the NITAG and the Ministry of Health. Nonetheless, in order to make the best use of HTA, the NITAG, as well as the Ministry of Health and all the involved stakeholders, should be adequately trained [100]. This could also lay the foundation for a stronger collaboration among relevant bodies and entities. Although international efforts already exist in this respect, parallel activities should be carried out at national level [78].
In fact, the importance of HTA in assessing vaccines is unquestionable and supported by the WHO guidelines on the introduction of new vaccines [19]. Furthermore, the European Regulation (EU) 2021/2282 on HTA [27] underlines the importance of HTA as a tool to ensure the timely introduction and use of new technologies, with a view to enhancing sustainability and the promotion of innovation. Prevention measures, including vaccines, are among the health technologies in scope of the regulation. For the clinical domains (the health problem, the current health technology, the technical characteristics of the health technology being evaluated, its safety and relative clinical effectiveness), joint and shared evaluation, namely the Joint Clinical Assessment (JCA), will be expected among European Member States. The latter should give due consideration to JCA, although complementary analyses could also be carried out at a national level. Anyway, the final decision to use health technologies will be entrusted to single Member States that are responsible for defining their health policy and the organisation and provision of health services and medical care. Therefore, non-clinical domains (the cost and economic assessment of health technology and its ethical, organisational, social, and legal aspects) will continue to be assessed at a national level because they are strongly dependent on the national context [27].
HTA will indeed remain a cornerstone of the vaccine-related decision-making process, which is currently complex, lengthy, and heterogeneous across European countries because of their different roles, decision-making criteria, and transparency of NITAGs and HTA bodies [28,31].
The findings of our work allow an overall view of the current maturity level of HTA for vaccines in Italy, in terms of both its conduction and applications.
A limitation of the study that should be considered is that in Italy the NIP is not updated on a regular basis. This can explain the late introduction of some vaccines with respect to the available HTA reports. In this context, some Italian regions also introduce vaccines into their regional immunization plan before the national recommendation, but our study did not capture this aspect. In addition, we only searched full HTA reports, and it should be considered that sometimes decisions are based only on partial evaluations, mostly economic assessment. The considered HTA reports did not issue formal recommendations on the use of specific vaccines, but synthetized the available evidence for different domains. For this reason, we did not include the results of each report, also because the objective was not to determine how the final decision was achieved. The latter is based on the appraisal of the HTA reports that could benefit from deliberative approaches too. Furthermore, in Italy, HTA reports on COVID-19 vaccination were not performed, even though immunization was introduced quickly, as soon as vaccines were available. Another limitation is represented by the choice to conduct the search for information about the use of HTA in the vaccine-related decision-making process using only national planning documents, namely the NIPs. In any case, the purpose of the study was to describe how HTA is considered within the field of national health planning, although it should be kept in mind that, because of local autonomy, regions can develop different vaccination strategies. Nonetheless, the NIP is the common base for the organization of vaccination strategies in all Italian regions. Another limitation is due to the fact that the study relies on a hand search performed on selected national journals that are well known in terms of the provision of such evidence. Eventually, no formal indicators were considered to address the impact of HTA [101,102,103,104,105,106], but this was reasoned by the fact that the work did not have the aim to monitor and evaluate the implementation of vaccination strategies [107]. Anyway, this topic could also merit further investigation with respect to the potential role of HTA in impacting several policy indicators.
The main strength of this study is that it provides an overall evaluation of the use of HTA in the landscape of vaccines that is currently missing in Italy. The findings highlight some critical issues in the application of this approach and can be useful for the future implementation of HTA in the issuing of Italian recommendations for vaccinations.

5. Conclusions

Our results highlight that HTA production in Italy is wide-ranging and continuous and can provide relevant information for the use of new vaccines, but can also be used to reassess already available and used ones. This evidence could respond to the evaluation needs emphasized in the national vaccine-relevant planning documents. Future research should elucidate how to conduct HTAs that fit the purpose of achieving quality and sustainable vaccination programs and provide timely support for vaccine-related decision-making, also considering the improvement of the transfer of HTA results to decision-makers and all relevant stakeholders.

Author Contributions

Conceptualization, S.B. and C.d.W.; methodology, S.B., R.R., D.P., G.E.C., P.A.C., G.G., C.F., P.B., W.R. and C.d.W.; formal analysis, S.B., R.R., D.P., G.E.C., P.A.C., G.G., C.F., P.B., W.R. and C.d.W.; investigation, S.B., R.R., D.P., G.E.C., P.A.C., G.G., C.F., P.B., W.R. and C.d.W.; data curation, S.B., R.R., D.P., G.E.C., P.A.C., G.G., C.F., P.B., W.R. and C.d.W.; writing—original draft, S.B. and C.d.W.; writing—review and editing, S.B., R.R., D.P., G.E.C., P.A.C., G.G., C.F., P.B., W.R. and C.d.W.; supervision, S.B. and C.d.W. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

No new data were created or analyzed in this study. Data sharing is not applicable to this article.

Conflicts of Interest

The authors declare no conflicts of interest.

References

  1. Susan; Plotkin, S. A short history of Vaccination. In Vaccines, 1st ed.; W.B. Saunders: Philadelphia, PA, USA, 1988. [Google Scholar]
  2. Pezzotti, P.; Bellino, S.; Prestinaci, F.; Iacchini, S.; Lucaroni, F.; Camoni, L.; Barbieri, M.M.; Ricciardi, W.; Stefanelli, P.; Rezza, G. The impact of immunization programs on 10 vaccine preventable diseases in Italy: 1900–2015. Vaccine 2018, 36, 1435–1443. [Google Scholar] [CrossRef] [PubMed]
  3. Roush, S.W.; Murphy, T.V.; Vaccine-Preventable Disease Table Working Group. Historical comparisons of morbidity and mortality for vaccine-preventable diseases in the United States. JAMA 2007, 298, 2155–2163. [Google Scholar] [CrossRef] [PubMed]
  4. Yu, W.; Lee, L.A.; Liu, Y.; Scherpbier, R.W.; Wen, N.; Zhang, G.; Zhu, X.; Ning, G.; Wang, F.; Li, Y.; et al. Vaccine-preventable disease control in the People’s Republic of China: 1949–2016. Vaccine 2018, 36, 8131–8137. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
  5. Song, Q.; Li, Y.; Cao, L.; Hao, L.; Wen, N.; Wang, F.; Ma, C.; Zhang, G.; Zheng, H.; Yu, W.; et al. Impact of National Immunization Strategies on Vaccine-Preventable Diseases—China, 1950–2021. China CDC Wkly. 2024, 6, 339–343. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
  6. Martin, L.J.; Galanis, I.; Lepp, T.; Lindstrand, A. Estimated number of reported vaccine-preventable disease cases averted following the introduction of routine vaccination programs in Sweden, 1910–2019. Eur. J. Public Health 2023, 33, 1188–1193. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
  7. Menzies, R.; Turnour, C.; Chiu, C.; McIntyre, P. Vaccine preventable diseases and vaccination coverage in Aboriginal and Torres Strait Islander people, Australia 2003 to 2006. Commun. Dis. Intell. Q. Rep. 2008, 32, S2–S67. [Google Scholar] [PubMed]
  8. Montero, D.A.; Vidal, R.M.; Velasco, J.; Carreño, L.J.; Torres, J.P.; Benachi, O.M.A.; Tovar-Rosero, Y.Y.; Oñate, A.A.; O’Ryan, M. Two centuries of vaccination: Historical and conceptual approach and future perspectives. Front. Public Health 2024, 11, 1326154. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
  9. Shattock, A.J.; Johnson, H.C.; Sim, S.Y.; Carter, A.; Lambach, P.; Hutubessy, R.C.W.; Thompson, K.M.; Badizadegan, K.; Lambert, B.; Ferrari, M.J.; et al. Contribution of vaccination to improved survival and health: Modelling 50 years of the Expanded Programme on Immunization. Lancet 2024, 403, 2307–2316. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
  10. Poria, R.; Kala, D.; Nagraik, R.; Dhir, Y.; Dhir, S.; Singh, B.; Kaushik, N.K.; Noorani, M.S.; Kaushal, A.; Gupta, S. Vaccine development: Current trends and technologies. Life Sci. 2024, 336, 122331. [Google Scholar] [CrossRef] [PubMed]
  11. Vecchio, R.; Gentile, L.; Tafuri, S.; Costantino, C.; Odone, A. Exploring future perspectives and pipeline progression in vaccine research and development. Ann. Ig. 2024, 36, 446–461. [Google Scholar] [CrossRef] [PubMed]
  12. Frost, I.; Sati, H.; Garcia-Vello, P.; Hasso-Agopsowicz, M.; Lienhardt, C.; Gigante, V.; Beyer, P. The role of bacterial vaccines in the fight against antimicrobial resistance: An analysis of the preclinical and clinical development pipeline. Lancet Microbe 2023, 4, e113–e125. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
  13. Brisse, M.; Vrba, S.M.; Kirk, N.; Liang, Y.; Ly, H. Emerging Concepts and Technologies in Vaccine Development. Front. Immunol. 2020, 11, 583077. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
  14. Li, T.; Qian, C.; Gu, Y.; Zhang, J.; Li, S.; Xia, N. Current progress in the development of prophylactic and therapeutic vaccines. Sci. China Life Sci. 2023, 66, 679–710. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
  15. Xue, W.; Li, T.; Gu, Y.; Li, S.; Xia, N. Molecular engineering tools for the development of vaccines against infectious diseases: Current status and future directions. Expert. Rev. Vaccines 2023, 22, 563–578. [Google Scholar] [CrossRef] [PubMed]
  16. Timmis, J.K.; Rigat, F.; Rappuoli, R. Core values for vaccine evaluation. Vaccine 2017, 35 (Suppl. S1), A57–A62. [Google Scholar] [CrossRef] [PubMed]
  17. Timmis, J.K.; Black, S.; Rappuoli, R. Improving accountability in vaccine decision-making. Expert. Rev. Vaccines 2017, 16, 1057–1066. [Google Scholar] [CrossRef] [PubMed]
  18. Donadel, M.; Panero, M.S.; Ametewee, L.; Shefer, A.M. National decision-making for the introduction of new vaccines: A systematic review, 2010–2020. Vaccine 2021, 39, 1897–1909. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
  19. World Health Organization. Principles and Considerations for Adding a Vaccine to a National Immunization Programme. From Decision to Implementation and Monitoring. Available online: https://www.who.int/publications/i/item/9789241506892 (accessed on 26 June 2024).
  20. World Health Organization. Vaccines Introduction Guidelines. Adding a Vaccine to a National Immunization Programme: Decision and Implementation; World Health Organization: Geneva, Switzerland, 2005. [Google Scholar]
  21. World Health Organization. Health Technology Assessment. Available online: https://www.who.int/health-topics/health-technology-assessment#tab=tab_1 (accessed on 29 August 2024).
  22. Agenas. HTA Health Technology Assessment. Available online: https://www.agenas.gov.it/aree-tematiche/hta-health-technology-assessment (accessed on 29 August 2024).
  23. O’Rourke, B.; Oortwijn, W.; Schuller, T.; International Joint Task Group. The new definition of health technology assessment: A milestone in international collaboration. Int. J. Technol. Assess. Health Care 2020, 36, 187–190. [Google Scholar] [CrossRef] [PubMed]
  24. Merlin, T.; Tamblyn, D.; Ellery, B.; INAHTA Quality Assurance Group. What’s in a name? Developing definitions for common health technology assessment product types of the International Network of Agencies for Health Technology Assessment (inahta). Int. J. Technol. Assess. Health Care 2014, 30, 430–437. [Google Scholar] [CrossRef] [PubMed]
  25. Kristensen, F.B.; Lampe, K.; Chase, D.L.; Lee-Robin, S.H.; Wild, C.; Moharra, M.; Garrido, M.V.; Nielsen, C.P.; Røttingen, J.A.; Neikter, S.A.; et al. Practical tools and methods for health technology assessment in Europe: Structures, methodologies, and tools developed by the European Network for Health Technology Assessment, EUnetHTA. Int. J. Technol. Assess. Health Care 2009, 25 (Suppl. S2), 1–8. [Google Scholar] [CrossRef] [PubMed]
  26. Kristensen, F.B.; Lampe, K.; Wild, C.; Cerbo, M.; Goettsch, W.; Becla, L. The HTA Core Model®-10 Years of Developing an International Framework to Share Multidimensional Value Assessment. Value Health 2017, 20, 244–250. [Google Scholar] [CrossRef] [PubMed]
  27. The European Parliament and the Council of the European Union, Regulation (EU) 2021/2282 of the European Parliament and of the Council of 15 December 2021 on Health Technology Assessment and Amending Directive 2011/24/EU2021 22.12.2021. Available online: https://eur-lex.europa.eu/legal-content/EN/TXT/PDF/?uri=CELEX:32021R2282&from=EN (accessed on 14 June 2024).
  28. Martinelli, D.; Quattrone, F.; Fortunato, F.; Di Maggio, E.; Filia, A.; Rota, M.C.; Lopalco, P.L.; Prato, R. Role of the National Immunisation Technical Advisory Groups in 13 European countries in the decision-making process on vaccine recommendations. Euro Surveill. 2023, 28, 2300131. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
  29. Largeron, N.; D’Agostino, P.; Chapman, R.; Danko, D.; Eskola, J.; Godfroid, P.; Feldmajer, G.; Hanley, R.; de Pouvourville, G.; Postma, M.; et al. Guiding Principles for Evaluating Vaccines in Joint Health Technology Assessment in the European Union: Preparing for the EU’s Regulation on HTA for Vaccines. Value Health 2024. ahead of print. [Google Scholar] [CrossRef] [PubMed]
  30. Silenzi, A.; Siddu, A.; D’Amelio, A.C.; Cataldi, S.; Fasano, C.; Maraglino, F.; Rezza, G.; Signorelli, C. The new Italian National Immunization Technical Advisory Group (NITAG) and its commitment to endorse a new efficient National Immunization Plan in COVID-19 times. Ann. Ist. Super. Sanita 2023, 59, 26–30. [Google Scholar] [CrossRef] [PubMed]
  31. Laigle, V.; Postma, M.J.; Pavlovic, M.; Cadeddu, C.; Beck, E.; Kapusniak, A.; Toumi, M. Vaccine market access pathways in the EU27 and the United Kingdom - analysis and recommendations for improvements. Vaccine 2021, 39, 5706–5718. [Google Scholar] [CrossRef] [PubMed]
  32. Bencina, G.; Fues Wahl, H.; Tsoumani, E.; Salomonsson, S. Recommendations and Health Technology Assessment (HTA) landscape evaluation for pediatric pneumococcal conjugate vaccines (PCV) in Europe: A systematic literature review. Hum. Vaccines Immunother. 2022, 18, 2060017. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
  33. Arya, S.; Norton, N.; Kaushik, P.; Brandtmüller, A.; Tsoumani, E. Recent changes to adult national immunization programs for pneumococcal vaccination in Europe and how they impact coverage: A systematic review of published and grey literature. Hum. Vaccines Immunother. 2023, 19, 2279394. [Google Scholar] [CrossRef]
  34. Noharet-Koenig, R.; Lasota, K.; Faivre, P.; Langevin, E. Evolution of Pneumococcal Vaccine Recommendations and Criteria for Decision Making in 5 Western European Countries and the United States. MDM Policy Pract. 2023, 8, 23814683231174432. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
  35. García-Mochón, L.; Espín Balbino, J.; Olry de Labry Lima, A.; Caro Martinez, A.; Martin Ruiz, E.; Pérez Velasco, R. HTA and decision-making processes in Central, Eastern and South Eastern Europe: Results from a survey. Health Policy 2019, 123, 182–190. [Google Scholar] [CrossRef] [PubMed]
  36. Cyr, P.R.; Jain, V.; Chalkidou, K.; Ottersen, T.; Gopinathan, U. Evaluations of public health interventions produced by health technology assessment agencies: A mapping review and analysis by type and evidence content. Health Policy 2021, 125, 1054–1064. [Google Scholar] [CrossRef] [PubMed]
  37. Ricciardi, W.; Tarricone, R. The evolution of the Italian National Health Service. Lancet 2021, 398, 2193–2206. [Google Scholar] [CrossRef] [PubMed]
  38. Italian Journal of Public Health. Available online: https://www.ijph.it/ (accessed on 30 August 2024).
  39. Journal of Preventive Medicine and Hygiene. Available online: https://www.jpmh.org/index.php/jpmh (accessed on 30 August 2024).
  40. The International Network of Agencies for Health Technology Assessment. INAHTA Product Type (IPT) Classifications & Marks. Available online: https://www.inahta.org/hta-tools-resources/ipt-marks/ (accessed on 5 August 2024).
  41. Ministero Della Salute. Piano Nazionale Vaccini 2005–2007. Available online: https://www.salute.gov.it/imgs/C_17_pubblicazioni_543_allegato.pdf (accessed on 30 August 2024).
  42. Ministero Della Salute. Piano Nazionale Prevenzione Vaccinale 2012–2014. Available online: https://www.salute.gov.it/imgs/C_17_pubblicazioni_1721_allegato.pdf (accessed on 14 June 2024).
  43. Ministero Della Salute. Piano Nazionale Prevenzione Vaccinale PNPV 2017–2019. 17 Gennaio 2017. Available online: https://www.salute.gov.it/imgs/C_17_pubblicazioni_2571_allegato.pdf (accessed on 14 June 2024).
  44. Presidenza del Consiglio dei Ministri. Conferenza Permanente per i Rapporti tra lo Stato, le Regioni e le Province Autonome di Trento e di Bolzano. Intesa, ai Sensi Dell’articolo 8, Comma 6, Della Legge 5 Giugno 2003, n. 131, tra il Governo, le Regioni e le Province Autonome di Trento e di Bolzano, sul Documento Recante «Piano Nazionale di Prevenzione Vaccinale (PNPV) 2023–2025» e sul Documento Recante «Calendario Nazionale Vaccinale». (Rep. atti n. 193/CSR del 2 agosto 2023). (23A04685) (G.U. Serie Generale, n. 194 del 21 Agosto 2023). Available online: https://www.trovanorme.salute.gov.it/norme/dettaglioAtto?id=95963&completo=true (accessed on 14 June 2024).
  45. Giuseppe La Torre, G.; Chiaradia, G.; Mannocci, A.; de Waure, C.; Ricciardi, W.; Capri, S.; Bamfi, F.; Bianchi, C.; Lapinet-Vera, J.; Marocco, A.; et al. Health Technology Assessment della vaccinazione anti-HPV. Ital. J. Public Health 2007, 5 (Suppl. S1), S1–S60. [Google Scholar]
  46. La Torre, G.; Chiaradia, G.; de Waure, C.; Nicolotti, N.; Monteduro, A. Report HTA del vaccino quadrivalente anti-HPV Gardasil. Ital. J. Public Health 2009, 6 (Suppl. S2), S1–S64. [Google Scholar]
  47. Favaretti, C.; Di Pietro, M.L.; Kheiraoui, F.; Capri, S.; Specchia, M.L.; Cadeddu, C.; Lovato, E.; Ferriero, A.M.; de Waure, C.; Poscia, A.; et al. Rivalutazione della vaccinazione anti-HPV a 5 anni dalla sua introduzione. HTA 2.0. Ital. J. Public Health 2014, 3, 1–136. [Google Scholar]
  48. Favaretti, C.; Kheiraoui, F.; de Waure, C.; Poscia, A.; Sacchini, D.; De Vincenzo, R.; Bechini, A.; Boccalini, S.; Bonanni, P.; Zanella, B.; et al. Il vaccino anti-HPV 9-valente: Report di Health Technology Assessment (HTA). Ital. J. Public Health 2017, 6, 142. [Google Scholar]
  49. Basile, M.; Bonanni, P.; Calabrò, G.E.; Carini, E.; Cicchetti, A.; Conversano, M.; De Vincenzo, R.; Favaretti, C.; Ghelardi, A.; Tafuri, S. Report di approfondimento e valutazione, con metodologia HTA (Health Technology Assessment), della vaccinazione anti-HPV nelle donne trattate per lesioni HPV-correlate. Ital. J. Public Health 2019, 8, 1–76. [Google Scholar]
  50. La Torre, G.; de Waure, C.; Capizzi, S.; Malaj, A.; Zollo, A.; Mantovani, L.G.; de Portu, S.; Cortesi, P.A.; Belisari, A.; Specchia, M.L.; et al. Rapporto di Health Technology Assessment della vaccinazione anti-pneumococcica con Prevenar 13. Ital. J. Public Health 2010, 7 (Suppl. S1), S1–S72. [Google Scholar]
  51. di Pietro, M.L.; Kheiraoui, F.; de Waure, C.; Specchia, M.L.; Cadeddu, C.; Capizzi, S.; Gualano, M.R.; Sferrazza, A.; Nicolotti, N.; Ferriero, A.M.; et al. Il vaccino pneumococcico 13-valente per la prevenzione delle infezioni da S. pneumoniae in età adulta: Una valutazione di HTA. Ital. J. Public Health 2013, 2, 1–112. [Google Scholar]
  52. Calabrò, G.E.; Vitale, F.; Rizzo, C.; Pugliese, A.; Boccalini, S.; Bechini, A.; Panatto, D.; Amicizia, D.; Domnich, A.; Amodio, E.; et al. Il nuovo vaccino coniugato antipneumococcico 15-valente per la prevenzione delle infezioni da S. pneumoniae in età pediatrica: Una valutazione di HTA [The new 15-valent pneumococcal conjugate vaccine for the prevention of S. pneumoniae infections in pediatric age: A Health Technology Assessment]. J. Prev. Med. Hyg. 2023, 64 (Suppl. S1), E1–E160. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
  53. Kheiraoui, F.; Cadeddu, C.; Quaranta, G.; Poscia, A.; Raponi, M.; de Waure, C.; Boccalini, S.; Pellegrino, E.; Bellini, I.; Pieri, L.; et al. Health Technology Assessment del vaccino antinfluenzale quadrivalente FLU-QIV (Fluarix Tetra®). Ital. J. Public Health 2015, 4, 1–88. [Google Scholar]
  54. Di Pietro, M.L.; Poscia, A.; Specchia, M.L.; de Waure, C.; Zace, D.; Gasparini, R.; Amicizia, D.; Lai, P.L.; Panatto, D.; Arata, L.; et al. Valutazione di Health Technology Assessment (HTA) del vaccino antinfluenzale adiuvato nella popolazione anziana italiana. Ital. J. Public Health 2017, 6, 1–104. [Google Scholar]
  55. Boccalini, S.; Bechini, A.; Innocenti, M.; Sartor, G.; Manzi, F.; Bonanni, P.; Panatto, D.; Lai, P.L.; Zangrillo, F.; Rizzitelli, E.; et al. La vaccinazione universale dei bambini contro l’influenza con il vaccino Vaxigrip Tetra® in Italia: Risultati di una valutazione di Health Technology Assessment (HTA) [The universal influenza vaccination in children with Vaxigrip Tetra® in Italy: An evaluation of Health Technology Assessment]. J. Prev. Med. Hyg. 2018, 59 (Suppl. S1), E1–E86, Italian. [Google Scholar] [PubMed] [PubMed Central]
  56. Calabrò, G.E.; Boccalini, S.; Del Riccio, M.; Ninci, A.; Manzi, F.; Bechini, A.; Bonanni, P.; Panatto, P.; Lai, P.L.; Amicizia, D.; et al. Valutazione di Health Technology Assessment (HTA) del vaccino antinfluenzale quadrivalente da coltura cellulare: Flucelvax Tetra. Ital. J. Public Health 2019, 8, 1–170. [Google Scholar]
  57. Calabrò, G.E.; Boccalini, S.; Bonanni, P.; Bechini, A.; Panatto, D.; Lai, P.L.; Amicizia, D.; Rizzo, C.; Ajelli, M.; Trentini, F.; et al. Valutazione di Health Technology Assessment (HTA) del vaccino antinfluenzale quadrivalente adiuvato: Fluad Tetra. Ital. J. Public Health 2021, 10, 1–168. [Google Scholar]
  58. Cicchetti, A.; Rumi, F.; Basile, M.; Orsini, F.; Gualano, M.R.; Bert, F.; Orsi, A.; Refolo, P.; Sacchini, D.; Casini, M.; et al. Report HTA del vaccino quadrivalente ad alto dosaggio (QIV-HD) EFLUELDA® per la prevenzione dell’influenza stagionale e delle sue complicanze nella popolazione over 65. Ital. J. Public Health 2021, 10, 1–170. [Google Scholar]
  59. Boccalini, S.; Pariani, E.; Calabrò, G.E.; De Waure, C.; Panatto, D.; Amicizia, D.; Lai, P.L.; Rizzo, C.; Amodio, E.; Vitale, F.; et al. Health Technology Assessment (HTA) dell’introduzione della vaccinazione antinfluenzale per la popolazione giovanile italiana con il vaccino Fluenz Tetra® [Health Technology Assessment (HTA) of the introduction of influenza vaccination for Italian children with Fluenz Tetra®]. J. Prev. Med. Hyg. 2021, 62 (Suppl. S1), E1–E118. (In Italian) [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
  60. Calabrò, G.E.; Boccalini, S.; Bechini, A.; Panatto, D.; Domnich, A.; Lai, P.L.; Amicizia, D.; Rizzo, C.; Pugliese, A.; Di Pietro, M.L.; et al. L’Health Technology Assessment come strumento value-based per la valutazione delle tecnologie sanitarie. Reassessment del vaccino antinfluenzale quadrivalente da coltura cellulare: Flucelvax Tetra® 2.0 [Health Technology Assessment: A value-based tool for the evaluation of healthcare technologies. Reassessment of the cell-culture-derived quadrivalent influenza vaccine: Flucelvax Tetra® 2.0]. J. Prev. Med. Hyg. 2023, 63 (Suppl. S1), E1–E140. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
  61. Favaretti, C.; Di Pietro, M.L.; Kheiraoui, F.; Capri, S.; Specchia, M.L.; Cadeddu, C.; Lovato, E.; Di Nardo, F.; Ferriero, A.M.; Mancuso, A.; et al. Health Technology Assessment della vaccinazione anti-rotavirus con il vaccino Rotarix. Ital. J. Public Health 2014, 3, 1–76. [Google Scholar]
  62. di Pietro, M.L.; Capri, S.; Kheiraoui, F.; de Waure, C.; Quaranta, G.; Poscia, A.; Specchia, M.L.; Veneziano, M.A.; Di Nardo, F.; Cadeddu, C.; et al. Health Technology Assessment della vaccinazione contro Meningococco B. Ital. J. Public Health 2013, 2, 1–115. [Google Scholar]
  63. Boccalini, S.; Bechini, A.; Sartor, G.; Paolini, D.; Innocenti, M.; Bonanni, P.; Panatto, D.; Lai, P.L.; Zangrillo, F.; Marchini, F.; et al. Health Technology Assessment (HTA) del vaccino anti-meningococco B (Trumenba®) per gli adolescenti in Italia [Health Technology Assessment of meningococcal B vaccine (Trumenba®) in adolescent in Italy]. J. Prev. Med. Hyg. 2019, 60 (Suppl. S2), E1–E94. (In Italian) [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
  64. Boccalini, S.; Panatto, D.; Mennini, F.S.; Marcellusi, A.; Bini, C.; Amicizia, D.; Lai, P.L.; Micale, R.T.; Frumento, D.; Azzari, C.; et al. Health Technology Assessment (HTA) sull’introduzione di coorti aggiuntive per la vaccinazione contro il meningococco con vaccini quadrivalenti coniugati in Italia [Health Technology Assessment (HTA) of the introduction of additional cohorts for anti-meningococcal vaccination with quadrivalent conjugate vaccines in Italy]. J. Prev. Med. Hyg. 2021, 62 (Suppl. S1), E1–E128. (In Italian) [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
  65. Agenzia Italiana del Farmaco. Gardasil. Riassunto Delle Caratteristiche del Prodotto. Available online: https://medicinali.aifa.gov.it/it/#/it/dettaglio/0000038990 (accessed on 6 August 2024).
  66. Agenzia Italiana del Farmaco. Cervarix. Riassunto Delle Caratteristiche del Prodotto. Available online: https://medicinali.aifa.gov.it/it/#/it/dettaglio/0000040609 (accessed on 6 August 2024).
  67. Agenzia Italiana del Farmaco. Gardasil 9. Riassunto Delle Caratteristiche del Prodotto. Available online: https://medicinali.aifa.gov.it/it/#/it/dettaglio/0000052289 (accessed on 6 August 2024).
  68. Sistema Nazionale Linee Guida dell’Istituto Superiore di Sanità. Linee Guida Condivise per la Prevenzione del Carcinoma Della Cervice Uterina. Follow-Up Post Trattamento CIN2 e CIN3. Raccomandazione: Vaccinazione Anti-HPV Post Trattamento. Linea Guida Pubblicata nel Sistema Nazionale Linee Guida, Roma, 21 Luglio 2020. Available online: https://www.iss.it/documents/20126/8403884/LLGG-197-GISCi_et_al-vaccino-HPV-20luglio_Racc1.pdf/1dd2f10e-0b5c-32d4-d917-bbd5e5ecbb7b?t=1678805433694 (accessed on 6 August 2024).
  69. Agenzia Italiana del Farmaco. Prevenar13. Riassunto Delle Caratteristiche del Prodotto. Available online: https://medicinali.aifa.gov.it/it/#/it/dettaglio/0000043359 (accessed on 6 August 2024).
  70. Agenzia Italiana del Farmaco. Vaxneuvance. Riassunto Delle Caratteristiche del Prodotto. Available online: https://medicinali.aifa.gov.it/it/#/it/dettaglio/0000062486 (accessed on 6 August 2024).
  71. Agenzia Italiana del Farmaco. Apexxna. Riassunto Delle Caratteristiche del Prodotto. Available online: https://medicinali.aifa.gov.it/it/#/it/dettaglio/0000062870 (accessed on 6 August 2024).
  72. Agenzia Italiana del Farmaco. Rotarix. Riassunto Delle Caratteristiche del Prodotto. Available online: https://medicinali.aifa.gov.it/it/#/it/dettaglio/0000038457 (accessed on 7 August 2024).
  73. Agenzia Italiana del Farmaco. RotaTeq. Riassunto Delle Caratteristiche del Prodotto. Available online: https://medicinali.aifa.gov.it/it/#/it/dettaglio/0000039277 (accessed on 7 August 2024).
  74. Agenzia Italiana del Farmaco. Bexero. Riassunto Delle Caratteristiche del Prodotto. Available online: https://medicinali.aifa.gov.it/it/#/it/dettaglio/0000049184 (accessed on 7 August 2024).
  75. Agenzia Italiana del Farmaco. Trumemba. Riassunto Delle Caratteristiche del Prodotto. Available online: https://medicinali.aifa.gov.it/it/#/it/dettaglio/0000054510 (accessed on 7 August 2024).
  76. Pollard, A.J.; Perrett, K.P.; Beverley, P.C. Maintaining protection against invasive bacteria with protein-polysaccharide conjugate vaccines. Nat. Rev. Immunol. 2009, 9, 213–220. [Google Scholar] [CrossRef] [PubMed]
  77. Blanchard-Rohner, G.; Pollard, A.J. Long-term protection after immunization with protein-polysaccharide conjugate vaccines in infancy. Expert. Rev. Vaccines 2011, 10, 673–684. [Google Scholar] [CrossRef] [PubMed]
  78. Hadler, S.C.; Shefer, A.M.; Cavallaro, K.F.; Ebama, M.; Tencza, C.; Kennedy, E.D.; Ndiaye, S.; Shah, A.; Torre, L.; Bresee, J.S. Supporting National Immunization Technical Advisory Groups (NITAGs) in development of evidence-based vaccine recommendations and NITAG assessments—New tools and approaches. Vaccine 2024. ahead of print. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
  79. Napolitano, F.; Ali Adou, A.; Vastola, A.; Angelillo, I.F. Rotavirus Infection and Vaccination: Knowledge, Beliefs, and Behaviors among Parents in Italy. Int. J. Environ. Res. Public. Health 2019, 16, 1807. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
  80. Costantino, C.; Restivo, V.; Tramuto, F.; Casuccio, A.; Vitale, F. Universal rotavirus vaccination program in Sicily: Reduction in health burden and cost despite low vaccination coverage. Hum. Vaccines Immunother. 2018, 14, 2297–2302. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
  81. Mita, V.; Arigliani, M.; Zaratti, L.; Arigliani, R.; Franco, E. Italian Physicians’ Opinions on Rotavirus Vaccine Implementation. Pathogens 2017, 6, 56. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
  82. Marchetti, F.; Vetter, V.; Conforti, G.; Esposito, S.; Bonanni, P. Parents’ insights after pediatric hospitalization due to rotavirus gastroenteritis in Italy. Hum. Vaccines Immunother. 2017, 13, 2155–2159. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
  83. Parez, N.; Giaquinto, C.; Du Roure, C.; Martinon-Torres, F.; Spoulou, V.; Van Damme, P.; Vesikari, T. Rotavirus vaccination in Europe: Drivers and barriers. Lancet Infect. Dis. 2014, 14, 416–425. [Google Scholar] [CrossRef] [PubMed]
  84. Alfonsi, V.; D’Ancona, F.; Giambi, C.; Nacca, G.; Rota, M.C.; Regional Coordinators for Infectious Diseases and Vaccinations. Current immunization policies for pneumococcal, meningococcal C, varicella and rotavirus vaccinations in Italy. Health Policy 2011, 103, 176–183. [Google Scholar] [CrossRef] [PubMed]
  85. Istituto Superiore di Sanità. Sorveglianza Delle Malattie Batteriche Invasive in Italia. Rapporto Consolidato 2017. Available online: https://www.iss.it/documents/20126/0/Rapporto+consolidato+MIB+2017.pdf/2fe47619-8d78-3754-0305-fb13d4ea02bd?t=1616753878331 (accessed on 30 August 2024).
  86. Istituto Superiore di Sanità. Sorveglianza Delle Malattie Batteriche Invasive in Italia. Rapporto Consolidato 2018. Available online: https://www.iss.it/documents/20126/0/Rapporto+consolidato+MIB+2018.pdf/b9a052fe-cfea-44aa-428a-7cd49c5bb3cb?t=1616753973449 (accessed on 30 August 2024).
  87. Istituto Superiore di Sanità. Sorveglianza Delle Malattie Batteriche Invasive in Italia. Rapporto Consolidato 2019. Available online: www.iss.it/documents/20126/0/Rapporto+consolidato+MIB+2019+%282%29.pdf/17f72afc-06df-151f-7265-9a9dc1af6caa?t=1616754116562 (accessed on 30 August 2024).
  88. Istituto Superiore di Sanità. Sorveglianza Delle Malattie Batteriche Invasive in Italia. Rapporto 2020. Available online: https://www.iss.it/documents/20126/0/Rapporto+MaBI+2020.pdf/a2d63000-2b68-56d9-bdf2-b471bd77417d?t=1644488786938 (accessed on 30 August 2024).
  89. Istituto Superiore di Sanità. Sorveglianza Delle Malattie Batteriche Invasive in Italia. Dati 2019–2021. Available online: https://www.iss.it/documents/20126/6996013/RIS-3_2022+new.pdf/e3a1d9b9-482a-6fdd-99af-022112ecf491?t=1674046780101 (accessed on 30 August 2024).
  90. Istituto Superiore di Sanità. Sorveglianza Delle Malattie Batteriche Invasive in Italia. Dati 2020–2022. Available online: https://www.iss.it/documents/20126/6703853/RIS-2_2023.pdf/ab5becbe-d2d8-ca12-b756-1e348b80c5a1?t=1698390273826 (accessed on 30 August 2024).
  91. Istituto Superiore di Sanità. Sorveglianza Delle Malattie Batteriche Invasive in Italia. Rapporto ad Interim. Periodo di Riferimento 1/01/2023–30/06/2023. Available online: https://www.iss.it/documents/20126/0/Rapporto+ad+interim+MaBI-primo+semestre+2023+%281%29.pdf/3d5dbe62-f389-5458-2f7c-c2a7fa952878?t=1710495649787 (accessed on 30 August 2024).
  92. Olbrich, K.J.; Müller, D.; Schumacher, S.; Beck, E.; Meszaros, K.; Koerber, F. Systematic Review of Invasive Meningococcal Disease: Sequelae and Quality of Life Impact on Patients and Their Caregivers. Infect. Dis. Ther. 2018, 7, 421–438. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
  93. Martinón-Torres, F. Deciphering the Burden of Meningococcal Disease: Conventional and Under-Recognized Elements. J. Adolesc. Health 2016, 59, S12–S20. [Google Scholar] [CrossRef] [PubMed]
  94. Tully, J.; Viner, R.M.; Coen, P.G.; Stuart, J.M.; Zambon, M.; Peckham, C.; Booth, C.; Klein, N.; Kaczmarski, E.; Booy, R. Risk and protective factors for meningococcal disease in adolescents: Matched cohort study. BMJ 2006, 332, 445–450. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
  95. Judge, D.; Nadel, S.; Vergnaud, S.; Garralda, M.E. Psychiatric adjustment following meningococcal disease treated on a PICU. Intensive Care Med. 2002, 28, 648–650. [Google Scholar] [CrossRef] [PubMed]
  96. Shears, D.; Nadel, S.; Gledhill, J.; Garralda, M.E. Short-term psychiatric adjustment of children and their parents following meningococcal disease. Pediatr. Crit. Care Med. 2005, 6, 39–43. [Google Scholar] [CrossRef] [PubMed]
  97. Ehrlich, T.R.; Von Rosenstiel, I.A.; Grootenhuis, M.A.; Gerrits, A.I.; Bos, A.P. Long-term psychological distress in parents of child survivors of severe meningococcal disease. Pediatr. Rehabil. 2005, 8, 220–224. [Google Scholar] [CrossRef] [PubMed]
  98. Bonanni, P.; Boccalini, S.; Zanobini, P.; Dakka, N.; Lorini, C.; Santomauro, F.; Bechini, A. The appropriateness of the use of influenza vaccines: Recommendations from the latest seasons in Italy. Hum. Vaccines Immunother. 2018, 14, 699–705. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
  99. Calabrò, G.E.; D’Ambrosio, F.; Fallani, E.; Ricciardi, W. Influenza Vaccination Assessment according to a Value-Based Health Care Approach. Vaccines 2022, 10, 1675. [Google Scholar] [CrossRef]
  100. de Labry Lima, A.O.; Mochon, L.G.; Martínez, A.C.; Ruiz, E.M.; Balbino, J.E. Mapping capacity to conduct health technology assessment in Central, Eastern and South-Eastern Europe. Croat. Med. J. 2016, 57, 66–70. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
  101. Cameron-Blake, E.; Tatlow, H.; Andretti, B.; Boby, T.; Green, K.; Hale, T.; Petherick, A.; Phillips, T.; Pott, A.; Wade, A.; et al. A panel dataset of COVID-19 vaccination policies in 185 countries. Nat. Hum. Behav. 2023, 7, 1402–1413. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
  102. Hale, T.; Angrist, N.; Goldszmidt, R.; Kira, B.; Petherick, A.; Phillips, T.; Webster, S.; Cameron-Blake, E.; Hallas, L.; Majumdar, S.; et al. A global panel database of pandemic policies (Oxford COVID-19 Government Response Tracker). Nat. Hum. Behav. 2021, 5, 529–538. [Google Scholar] [CrossRef] [PubMed]
  103. Yuan, B. The application of policy composite indicators to predicting the health risk and recovery: A global comparative investigation. Public. Health 2023, 224, 209–214. [Google Scholar] [CrossRef] [PubMed]
  104. Chen, Z.; Zheng, W.; Wu, Q.; Chen, X.; Peng, C.; Tian, Y.; Sun, R.; Dong, J.; Wang, M.; Zhou, X.; et al. Global diversity of policy, coverage, and demand of COVID-19 vaccines: A descriptive study. BMC Med. 2022, 20, 130. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
  105. Mathieu, E.; Ritchie, H.; Ortiz-Ospina, E.; Roser, M.; Hasell, J.; Appel, C.; Giattino, C.; Rodés-Guirao, L. A global database of COVID-19 vaccinations. Nat. Hum. Behav. 2021, 5, 947–953. [Google Scholar] [CrossRef] [PubMed]
  106. van Kessel, R.; Forman, R.; Milstein, R.; Mastylak, A.; Czabanowska, K.; Czypionka, T.; Durand-Zaleski, I.; Hirche, A.; Krysinska-Pisarek, M.; Maynou, L.; et al. Divergent COVID-19 vaccine policies: Policy mapping of ten European countries. Vaccine 2023, 41, 2804–2810. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
  107. Marzouk, M.; Omar, M.; Sirison, K.; Ananthakrishnan, A.; Durrance-Bagale, A.; Pheerapanyawaranun, C.; Porncharoen, C.; Pimsarn, N.; Lam, S.T.; Ung, M.; et al. Monitoring and Evaluation of National Vaccination Implementation: A Scoping Review of How Frameworks and Indicators Are Used in the Public Health Literature. Vaccines 2022, 10, 567. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
Table 1. HTA reports on vaccination published in Italy in the period 2007–2023.
Table 1. HTA reports on vaccination published in Italy in the period 2007–2023.
YearHTA ReportVaccineTarget Population/Vaccination StrategyReference
HPV vaccines
2007Health Technology
Assessment of anti-HPV vaccination		HPV2Female adolescents (12 years old)[45]
2009HTA report of the quadrivalent anti-HPV vaccine GardasilHPV4Female adolescents (12 years old)[46]
2014Revaluation of anti-HPV vaccination 5 years after its introduction. HTA 2.0HPVFemale adolescents (12 years old)/two-dose versus three-dose schedule[47]
2017The anti-HPV 9-Valent vaccine: Health Technology Assessment (HTA) reportHPV9Adolescents (12 years old)[48]
2019In-depth report and evaluation, using HTA (Health Technology Assessment) methodology, of anti-HPV vaccination in women treated for HPV-related injuriesHPVWomen treated for HPV-related injuries[49]
Pneumococcal conjugate vaccines
2010Report of Health Technology Assessment of anti-pneumococcal vaccination with Prevenar 13PCV13Paediatric population[50]
2013The 13-valent pneumococcal vaccine for the prevention of adult S. pneumoniae infections: an evaluation of HTAPCV13Older population[51]
2023The new 15-valent antipneumococcic conjugate vaccine for the prevention of S. pneumoniae infections in children: an assessment of HTAPCV15Paediatric population[52]
Influenza vaccines
2015Health Technology Assessment of the FLU-QIV quadrivalent influenza vaccine (Fluarix Tetra)Flu QIVGeneral population/quadrivalent vaccine versus trivalent vaccine [53]
2017Health Technology Assessment (HTA) of the adjuvant influenza vaccine in the elderly Italian populationFlu aTIVOlder population[54]
2018Universal vaccination of children against influenza with the vaccine Vaxigrip Tetra in ItalyFlu QIV paediatric populationPaediatric vaccination[55]
2019Health Technology Assessment (HTA) of the Flucelvax Tetra cell culture quadrivalent influenza vaccineFlu ccQIV General population[56]
2021Health Technology Assessment (HTA) of the adjuvant quadrivalent influenza vaccine: Fluad TetraFlu aQIVOlder population[57]
2021HTA report of the EFLUELDA high-dose quadrivalent vaccine (QIV-HD) for the prevention of seasonal influenza and its complications in the over-65 populationFlu hdQIVOlder population[58]
2021Health Technology Assessment (HTA) of the introduction of flu vaccination for the Italian youth population with the vaccine Fluenz TetraFlu LAIVPaediatric population[59]
2023The Health Technology Assessment as a value-based tool for evaluating healthcare technologies Reassessment of quadrivalent cell culture influenza vaccine: Flucelvax Tetra 2.0Flu ccQIV General population [60]
Rotavirus vaccine
2014Health Technology Assessment of Rotavirus vaccination with the Rotarix vaccineRotavirusInfant population[61]
Meningococcal vaccines
2013Health Technology Assessment of vaccination against Meningococcus BQuadrivalent MenBInfant population[62]
2019Health Technology Assessment of meningococcal B vaccine (Trumenba®) in adolescents in ItalyBivalent MenBAdolescents[63]
2021Health Technology Assessment (HTA) on the introduction of additional cohorts for vaccination against meningococcus with quadrivalent conjugated vaccines in ItalyMenACWY2-cohort strategy (subjects of 13–15 months and 11 years) versus 4-cohort strategy (subjects of 13–15 months, 6 years, 11 years, and 19 years of age)[64]
Note: HPV2: bivalent HPV vaccine; HPV4: quadrivalent HPV vaccine; HPV: HPV vaccine; HPV9: 9-valent HPV vaccine; PCV13: 13-valent conjugate vaccine; PCV15: 15-valent conjugate vaccine; Flu QIV: quadrivalent inactivated influenza vaccine; Flu aTIV: trivalent inactivated adjuvated influenza vaccine; Flu ccQIV: quadrivalent inactivated cellular culture influenza vaccine; Flu aQIV: quadrivalent inactivated adjuvated influenza vaccine; Flu hdQIV: quadrivalent inactivated high dose influenza vaccine; Flu LAIV: live attenuated influenza vaccine; Rotavirus: rotavirus vaccine; Quadrivalent MenB: quadrivalent meningococcal B vaccine; Bivalent MenB: bivalent meningococcal B vaccine; MenACWY: meningococcal ACWY vaccine.
Table 2. HTA reports on influenza vaccination: year of publication, influenza season of vaccine availability, and national recommendation.
Table 2. HTA reports on influenza vaccination: year of publication, influenza season of vaccine availability, and national recommendation.
HTA ReportVaccineYear of Report PublicationFirst Influenza Season of Vaccine Availability and National Recommendation 1Vaccination Program/Extension of the Indications of Use
Assessment of the health technology of the FLU-QIV quadrivalent influenza vaccine (Fluarix Tetra) [53]Flu QIV20152014–2015
Health Technology Assessment (HTA) of the adjuvant influenza vaccine in the elderly Italian population [54]Flu TIVa20171997–1998
Universal vaccination of children against influenza with the vaccine Vaxigrip Tetra in Italy [55]Flu QIV paediatric population2018-Pediatric vaccination program from 2020–2021 influenza season
Health Technology Assessment (HTA) of the Flucelvax Tetra cell culture quadrivalent influenza vaccine [56]Flu QIVcc20192019–2020
Health Technology Assessment (HTA) of the adjuvant quadrivalent influenza vaccine: Fluad Tetra [57]Flu QIVa20212021–2022
HTA report of the EFLUELDA high-dose quadrivalent vaccine (QIV-HD) for the prevention of seasonal influenza and its complications in the over-65 population [58]Flu QIVhd20212020–2021
Health Technology Assessment (HTA) of the introduction of flu vaccination for the Italian youth population with the vaccine Fluenz Tetra [59]Flu LAIV20212021–2022
The Health Technology Assessment as a value-based tool for evaluating healthcare technologies Reassessment of quadrivalent cell culture influenza vaccine: Flucelvax Tetra 2.0 [60]Flu QIVcc20232021–20222021: extension of the indications of use ≥2 years of age
1 Annual Ministerial Circular for the prevention and the control of seasonal influenza.
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Boccalini, S.; Ragusa, R.; Panatto, D.; Calabrò, G.E.; Cortesi, P.A.; Giorgianni, G.; Favaretti, C.; Bonanni, P.; Ricciardi, W.; de Waure, C. Health Technology Assessment of Vaccines in Italy: History and Review of Applications. Vaccines 2024, 12, 1090. https://doi.org/10.3390/vaccines12101090

AMA Style

Boccalini S, Ragusa R, Panatto D, Calabrò GE, Cortesi PA, Giorgianni G, Favaretti C, Bonanni P, Ricciardi W, de Waure C. Health Technology Assessment of Vaccines in Italy: History and Review of Applications. Vaccines. 2024; 12(10):1090. https://doi.org/10.3390/vaccines12101090

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Boccalini, Sara, Rosalia Ragusa, Donatella Panatto, Giovanna Elisa Calabrò, Paolo Angelo Cortesi, Gabriele Giorgianni, Carlo Favaretti, Paolo Bonanni, Walter Ricciardi, and Chiara de Waure. 2024. "Health Technology Assessment of Vaccines in Italy: History and Review of Applications" Vaccines 12, no. 10: 1090. https://doi.org/10.3390/vaccines12101090

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