Efficacy and safety of mRNA1273 SARS-CoV-2 vaccination in hematopoietic stem cell transplant recipients: Single center experience

Background: COVID-19 represents a worldwide pandemic and vaccination remains the most effective preventive strategy. Among hematological patients, COVID-19 has been associated with a high mortality rate. Vaccination against SARS-CoV-2 has shown high efficacy in reducing community transmission, hospitalization and deaths related to severe COVID-19 disease. However, patients with impaired immunity may have lower sero-responsiveness to vaccination.MethodsThis study focuses on hematopoietic stem cell transplantation (HSCT) recipients. We performed a unicenter, prospective, observational study of a cohort of 31 allogeneic and 56 autologous-HSCT recipients monitored between March 2021 and May 2021 for serological response after COVID-19 vaccination with two doses of mRNA1273 vaccine (Moderna). In order to determine seroconversion, serological status before vaccination was studied.ResultsAt a median range of 75 days after the second vaccine dose, seroconversion rates were 84% and 85% for the autologous and allogeneic-HSCT groups, respectively. We confirmed some potential risk factors for a negative serological response, such as receiving anti-CD20 therapy in the previous year before vaccination, a low B-lymphocyte count and hypogammaglobulinemia. Neutralizing antibodies were quantified in 44 patients, with a good correlation with serological tests. Adverse events were minimal.ConclusionmRNA1273 vaccination is safe and effective in HSCT recipients, especially in those presenting recovered immunity. (AU)

Introducción: Entre los pacientes hematológicos, la COVID-19 se ha asociado a una mayor mortalidad. La vacunación frente a SARS-CoV-2 es la principal estrategia de prevención y ha demostrado eficacia en la reducción de la transmisión, de la hospitalización y de la tasa de mortalidad. Aun así, los pacientes oncohematológicos con un sistema inmunológico disfuncional podrían presentar una respuesta menor a la vacunación.MétodosEstudio unicéntrico, prospectivo y observacional, con una cohorte de 31 receptores de un trasplante alogénico de progenitores hematopoyéticos y de 56 receptores de un trasplante autólogo que recibieron la vacunación frente a SARS-CoV-2 entre marzo de 2021 y mayo de 2021, con 2 dosis de la vacuna mRNA1273 (Moderna). Para poder determinar la tasa de seroconversión, se determinó el estado serológico previamente a la vacunación y posteriormente se monitorizó la respuesta serológica.ResultadosCon un tiempo medio de seguimiento de 75 días después de la segunda vacuna, la tasa de seroconversión fue del 84%, y del 85% en el grupo receptor de trasplante autólogo y alogénico, respectivamente. Se confirmaron algunos potenciales factores de riesgo para la ausencia de respuesta serológica, como haber recibido terapias anti-CD20, un recuento bajo de linfocitos B y la hipogammaglobulinemia. En 44 pacientes se cuantificaron títulos de anticuerpos neutralizantes, con buena correlación con los test serológicos. Los efectos adversos de la vacuna fueron mínimos.ConclusiónLa vacunación con mRNA1273 es segura y efectiva en los pacientes receptores de un trasplante de progenitores hematopoyéticos, especialmente en los que presentan reconstitución inmune previa. (AU)

COVID-19 Vaccine Injury Compensation Program: Lessons Learned From a Review of 10 Implementing Countries.

National vaccine injury compensation serves as a crucial and significant safety net for individuals affected by government-recommended vaccines during a pandemic, contributing to the community's overall safety. In the Republic of Korea, compensation for adverse events resulting from coronavirus disease 2019 (COVID-19) vaccinations has been provided through the National Vaccine Injury Compensation Program introduced in 1995. However, there have been limitations with these measures during the COVID-19 pandemic owing to strict criteria for substantiating causality between the vaccine and injury, its nontransparent process of determining whether to compensate, and the compensation amount that is not practically calculated. This article reviewed the Vaccine Injury Compensation Programs in 10 major countries to present implications for improving the Korean system. Expanding the scope of national accountability is essential to compensate for the consequences of adhering to national policies during public health crises. Therefore, valuable insight can be obtained from examining the systems in Germany, Japan, and Taiwan, which have implemented more relaxed criteria for determining causality in compensation cases; Thailand's system, which provides the mandatory payment of preliminary compensation for damage caused by vaccination; systems in Germany, France, and Japan, which offer compensation for vaccine injuries from a practical perspective; and systems in France and the United Kingdom, which have a process allowing the assessment records to be shared with the claimants. Furthermore, a dedicated agency for vaccine injury compensation, as seen in France, the United Kingdom, and Australia, is necessary to enhance the efficiency of the Korean system.

Collaboration within the global vaccine safety surveillance ecosystem during the COVID-19 pandemic: lessons learnt and key recommendations from the COVAX Vaccine Safety Working Group.

This analysis describes the successes, challenges and opportunities to improve global vaccine safety surveillance as observed by the Vaccine Safety Working Group from its role as a platform of exchange for stakeholders responsible for monitoring the safety of vaccines distributed through the COVAX mechanism. Three key elements considered to be essential for ongoing and future pandemic preparedness for vaccine developers in their interaction with other members of the vaccine safety ecosystem are (1) the availability of infrastructure and capacity for active vaccine safety surveillance in low-income and middle-income countries (LMICs), including the advancement of concepts of safety surveillance and risk management to vaccine developers and manufacturers from LMICs; (2) more comprehensive mechanisms to ensure timely exchange of vaccine safety data and/or knowledge gaps between public health authorities and vaccine developers and manufacturers; and (3) further implementation of the concept of regulatory reliance in pharmacovigilance. These aims would both conserve valuable resources and allow for more equitable access to vaccine safety information and for benefit/risk decision-making.

The Vaccine Training Barometer: Assessing healthcare providers' confidence to answer vaccine-related questions and their training needs.

Healthcare providers (HCP) are seen by the public as the most trustworthy source of information about vaccination. While HCPs could be a valuable partner to increase vaccine confidence in general, it is not clear whether they feel confident themselves to address questions concerning vaccination. In the context of the EU Joint Action on Vaccination (EU-JAV), the Vaccine Training Barometer, an online survey tool, was developed to assess how frequently HCPs receive questions about vaccination, how confident they feel to answer these questions, and to what extent they are willing to follow extra training. After a pilot test in Flanders, Belgium, the Barometer was launched and completed by 833 HCPs in Flanders and 291 HCPs in the Spanish regions of Catalonia, Navarre and Valencian Community from November 2020 until January 2021, during the COVID-19 pandemic, just before and during the start of the first COVID-19 vaccination campaigns. In both countries, HCPs frequently received questions about vaccination (mostly on a daily or weekly basis), and about two thirds of them indicated that the frequency of questions had increased during the three months prior to completing the survey. Most questions were about the side effects and safety of vaccines. In both countries, a considerable proportion of HCPs did not feel confident to answer vaccine-related questions (31.5% felt confident in Flanders, 21.6% in Spain). A large proportion of HCPs received questions in the last three months before the survey that they could not answer (52.4% of respondents in Flemish sample, 41.5% in Spanish sample). Only 11.4% (Flanders) and 11.3% (Spain) of the respondents felt they gained sufficient knowledge through their standard education to be able to answer questions about vaccination. Almost all respondents were willing to follow extra training on vaccination (Flanders: 95.4%, Spain: 96.6%). The Vaccine Training Barometer is thus a useful tool to monitor HCPs' confidence to answer questions about vaccination and to capture their training needs.

Adverse events following immunisation: Prospective cohort study evaluating Australian children presenting to specialist immunisation clinics.

OBJECTIVE: Prior experience of an adverse event following immunisation is a known barrier to vaccination. Limited Australian data evaluating adverse event recurrence among children exists to inform clinical decisions. We aimed to assess adverse event following immunisation recurrence among children with prior adverse events and to evaluate if family history increased adverse event risk. METHODS: A prospective cohort study was conducted from March 3rd until August 18th, 2023. Children ≤ 16 years with prior adverse events following immunisation in themselves or family were recruited from specialist immunisation clinics at two quaternary paediatric hospitals. Adverse event outcomes were collected via surveys administered at presentation, three, and eight days post vaccination, and analysed by key characteristics and potential risk factors. RESULTS: Forty three of forty nine (43/49, 87.8 %) children enrolled received further vaccines. Of those who completed the follow up surveys, 50.0 % (16/32) reported an adverse event. Recurrence of prior adverse events occurred for 23.3 % (10/43, 95 % CI: 11.8 % - 38.6 %) of the cohort. Two of twelve (2/12, 16.7 %) participants with prior serious adverse events who received further vaccines reported a serious adverse event recurrence. No post review serious adverse events were observed in children with prior non serious adverse events. Neurological conditions were a risk factor for prior (neurological condition 3/3 versus no neurological condition 2/40, p < 0.001) and post review (neurological condition 2/3 versus no neurological condition 0/28, p = 0.006) post vaccination seizures. Family history had no relationship to post review adverse events (family history 5/8 versus no family history 11/23, p = 0.685). CONCLUSION: Revaccination is safe for the majority of children with a personal or family history of adverse event following immunisation.

Development and validation of VaxConcerns: A taxonomy of vaccine concerns and misinformation with Crowdsource-Viability.

We present VaxConcerns, a taxonomy for vaccine concerns and misinformation. VaxConcerns is an easy-to-teach taxonomy of concerns and misinformation commonly found among online anti-vaccination media and is evaluated to produce high-quality data annotations among crowdsource workers, opening the potential adoption of the framework far beyond just academic or medical communities. The taxonomy shows high agreement among experts and outperforms existing taxonomies for vaccine concerns and misinformation when presented to non-expert users. Our proof-of-concept study on the changes in anti-vaccination content during the COVID-19 pandemic indicate impactful future use cases, such as longitudinal studies of the shift in vaccine concerns over time.

Thrombosis with thrombocytopenia syndrome (TTS) and vaccine-induced immune thrombocytopenia and thrombosis (VITT): Brighton Collaboration case definitions and guidelines for data collection, analysis, and presentation of immunisation safety data.

This is a revision of the online November 2021 Brighton thrombosis with thrombocytopenia syndrome (TTS) case definition and a new Brighton Collaboration case definition for vaccine-induced immune thrombocytopenia and thrombosis (VITT). These case definitions are intended for use in clinical trials and post-licensure pharmacovigilance activities to facilitate safety data comparability across multiple settings. They are not intended to guide clinical management. The case definitions were developed by a group of subject matter and Brighton Collaboration process experts as part of the Coalition for Epidemic Preparedness Innovations (CEPI)-funded Safety Platform for Evaluation of vACcines (SPEAC). The case definitions, each with defined levels of diagnostic certainty, are based on relevant published evidence and expert consensus and are accompanied by specific guidelines for TTS and VITT data collection and analysis. The document underwent peer review by a reference group of vaccine safety stakeholders and haematology experts to ensure case definition useability, applicability and scientific integrity.

Misinformation and the Vaccine Adverse Event Reporting System.

This Viewpoint posits that to improve public understanding of the system, the Vaccine Adverse Event Reporting System (VAERS) could use a more accurate name, well-defined guidance about the reporting system's nature and use, and comprehensible information about an event's verification status.

The risk of acute disseminated encephalomyelitis (ADEM) following covid-19 vaccination in England: A self-controlled case-series analysis.

Acute disseminated encephalomyelitis (ADEM) has been identified as an Adverse Event of Special Interest in the COVID-19 vaccine programme due to its long-standing temporal association with a wide range of other vaccines. Case reports of ADEM shortly following COVID-19 vaccination have now been documented. There were 217 ADEM admissions in 215 individuals in the period 8th December 2020 to 31st March 2023. An increased risk of ADEM following the first dose of ChAdOx1 vaccine was observed (relative incidence (RI) = 3.13, 95% Confidence Interval (CI) [1.56-6.25]) with a vaccine attributable risk of 0.39 per million doses. When doses 1 and 2 were combined this increased risk remained just significant (1.96 [95%CI 1.01-3.82]). No significant increased risk was observed with any other vaccine or dose. This small, elevated risk after the first dose of ChAdOx1-S vaccine demonstrates how large national electronic datasets can be used to identify very rare risks and provides reassurance that any risk of ADEM following the ChAdOx1-S COVID-19 vaccination is extremely small. Given the rarity of this risk, further studies in settings with access to data on large populations should be carried out to verify these findings.

Obstetric and neonatal outcomes in South Africa.

BACKGROUND: Background epidemiologic population data from low- and middle-income countries (LMIC), on maternal, foetal and neonatal adverse outcomes are limited. We aimed to estimate the incidence of maternal, foetal and neonatal adverse outcomes at South African maternal vaccine trial sites as reported directly in the clinical notes as well as using the 'Global Alignment of Immunization Safety Assessment in Pregnancy' case definitions (GAIA-CDs). GAIA-CDs were utilized as a tool to standardise data collection and outcome assessment, and the applicability and utility of the GAIA-CDs was evaluated in a LMIC observational study. METHODS: We conducted a retrospective record review of maternity and neonatal case records for births that occurred in Soweto, Inner City- Johannesburg and Metro-East Cape Town, South Africa, between 1st July 2017 and 30th June 2018. Study staff abstracted data from randomly selected medical charts onto standardized study-specific forms. Incidence (per 100,000 population) was calculated for adverse maternal, foetal and neonatal outcomes, which were identified as priority outcomes in vaccine safety studies by the Brighton Collaboration and World Health Organization. Outcomes reported directly in the clinical notes and outcomes which fulfilled GAIA-CDs were compared. Incidence of outcomes was calculated by combining cases which were either reported in clinical notes by attending physicians and/ or fulfilled GAIA-CDs. FINDINGS: Of 9371 pregnant women enrolled, 27·6% were HIV-infected, 19·9% attended antenatal clinic in the 1st trimester of pregnancy and 55·3% had ≥1 ultrasound examination. Fourteen percent of women had hypertensive disease of pregnancy, 1·3% had gestational diabetes mellitus and 16% experienced preterm labour. There were 150 stillbirths (1·6%), 26·8% of infants were preterm and five percent had microcephaly. Data available in clinical notes for some adverse outcomes, including maternal- & neonatal death, severe pre-eclampsia/ eclampsia, were able to fulfil GAIA-CDs criteria for all of the clinically-reported cases, however, missing data required to fulfil other GAIA-CD criteria (including stillbirth, gestational diabetes mellitus and gestational hypertension) led to poor correlation between clinically-reported adverse outcomes and outcomes fulfilling GAIA-CDs. Challenges were also encountered in accurately ascertaining gestational age. INTERPRETATION: This study contributes to the expanding body of data on background rates of adverse maternal and foetal/ neonatal outcomes in LMICs. Utilization of GAIA-CDs assists with alignment of data, however, some GAIA-CDs require amendment to improve the applicability in LMICs. FUNDING: This study was funded by Pfizer (Inc).

Lessons learned from COVID-19, H1N1, and routine vaccine pharmacovigilance in the United States: a path to a more robust vaccine safety program.

INTRODUCTION: Vaccine pharmacovigilance is an essential component of vaccine safety programs. Vaccine pharmacovigilance refers to detecting uncommon adverse events following immunization (AEFI), determining whether they are due to the vaccine or are only a coincidence, and, for those AEFI considered related to vaccination, characterizing them further. When AEFI are due to vaccination, it is important to characterize the attributable risk and ascertain the biological mechanism causing the adverse reaction to inform efforts to prevent or mitigate the risk. A robust post-authorization safety system is necessary for vaccine decision-making, clinical recommendations, vaccine compensation, and vaccine communication and confidence. AREAS COVERED: This paper describes the key characteristics of vaccine pharmacovigilance programs, reviews US vaccine pharmacovigilance for routine vaccination programs, COVID-19, and H1N1, and makes recommendations for improving future vaccine safety systems. EXPERT OPINION: The key characteristics of vaccine pharmacovigilance programs include passive surveillance, active surveillance, clinical investigation and special studies, and causality assessment. Recent examples illustrate the strengths of US pharmacovigilance systems, including systems for passive and active surveillance, as well as areas for improvement, including study of pathogenesis, consistent funding, and leadership. We make recommendations that would, if implemented, further strengthen the vaccine safety system for future routine and pandemic immunizations.

Adverse events following immunization reported with COVID-19 vaccines in Burkina Faso: Analysis of spontaneous reports / Manifestations post-vaccinales indésirables rapportées avec les vaccins anti-COVID-19 au Burkina Faso : analyse des notifications spontanées

The rapid deployment of COVID-19 vaccines to a large proportion of the population requires a focus on safety. However, few studies have assessed the safety of COVID-19 vaccines in Africa. In Burkina Faso, this issue has not yet been addressed. The objective of this study was to contribute to the description of the characteristics of adverse events following immunization (AEFIs) related to COVID-19 vaccines in Burkina Faso. This was a cross-sectional descriptive retrospective study of spontaneous reports of COVID-19 vaccine-related AEFIs recorded in VigiBase® between June 2021 and November 2022 in Burkina Faso. Individual case safety reports (ICSRs) were extracted from VigiBase® using the Anatomical Therapeutic Chemical level 2 (ATC2) code. The proportion of ICSRs according to the reporter's qualification, the reporting rate, the time taken to submit and record ICSRs, and the completeness score were calculated. A total of 973 ICSRs concerned COVID-19 vaccines and represented 32.6% of all 2,988 reports in VigiBase®. Overall, 82.0% of the reporters were nurses/midwives, 7.8% were physicians, 6.7% were pharmacists, and 3.4% were patients. The median time between the onset of AEFIs and the submission of the report to the Pharmacovigilance Center was 180 days (IQR: 136; 281). The median registration time was 188 days (IQR: 149; 286). The mean ICSR completeness score was 0.8 (standard deviation = 0.1). The overall AEFI reporting rate was 27.8 per 100,000 vaccine doses. The AEFI reporting rates for the ChAdOx1-nCoV-19, JNJ 78436735, Elasomeran, Tozinameran, and HB02 vaccines were 454.2, 17.4, 11.0, 10.2, and 0.4 per 100,000 vaccine doses, respectively. The majority of AEFIs were systemic in nature (90.1%). Headache (21.2%), fever (19.4%), and myalgia (11.0%) were the most frequently reported AEFIs. Eighteen cases (1.8%) of serious AEFIs (9 hospitalizations, 4 life threatening, 3 temporary disabilities, and 2 others unspecified) were reported. The majority of AEFIs reported were systemic in nature and mild. However, there have been reports of serious AEFIs. The overall AEFI reporting rate was low. There is a need to strengthen the monitoring of these vaccines to better organize strategies to optimize the adherence of the population of Burkina Faso.

Le déploiement rapide des vaccins anti COVID-19 sur une grande partie de la population nécessite de mettre l'accent sur la sécurité. Cependant, peu d'études ont évalué la sécurité des vaccins anti COVID-19 en Afrique. Au Burkina Faso, cette question n'a pas encore été abordée. La présente étude avait pour objectif de contribuer à la description des caractéristiques des manifestations post-vaccinales indésirables (MAPI) liées aux vaccins anti COVID-19 au Burkina Faso. Il s'est agi d'une étude transversale rétrospective ayant porté sur les notifications de MAPI liées aux vaccins anti COVID-19 enregistrées dans VigiBase® entre juin 2021 et novembre 2022 au Burkina Faso. Les cas individuels de rapports de sécurité (CIRS) ont été extraits de VigiBase® à l'aide du code Anatomical Therapeutic Chemical niveau 2 (ATC2). La proportion de CIRS selon la qualification du notificateur, le taux de notification, le délai de transmission et d'enregistrement des CIRS et le score d'exhaustivité ont été calculés. Au total 973 CIRS concernaient les vaccins anti COVID-19 et représentaient 32,6 % des 2 988 rapports enregistrés dans VigiBase®. La répartition des notifications en fonction de la qualification du notificateur a montré que 82,0 % étaient des infirmiers/sage femmes, 7,8 % des médecins, 6,7 % des pharmaciens et 3,4 % des patients. Le délai médian entre l'apparition des MAPI et la transmission du rapport au Centre de pharmacovigilance était de 180 jours (IQR : 136 ; 281). Le délai médian d'enregistrement était de 188 jours (IQR : 149 ; 286). Le score d'exhaustivité moyen des CIRS était de 0,8 (écart type = 0,1). Le taux global de notifications des MAPI était de 27,8 pour 100 000 doses de vaccins. Les taux de notification des MAPI pour les vaccins ChAdOx1-nCoV-19, JNJ 78436735, Elasomeran, Tozinameran et HB02 étaient de 454,2 ; 17,4 ; 11,0 ; 10,2 et 0,4 pour 100 000 doses, respectivement. La majorité des MAPI était de manifestation systémique (90,1 %). Les céphalées (21,2 %), la fièvre (19,4 %) et les myalgies (11,0 %) étaient les MAPI les plus fréquemment notifiés. Dix-huit cas (1,8 %) de MAPI graves (9 hospitalisations, 4 mises en jeu du pronostic vital, 3 incapacités temporaires et 2 autres non précisés) ont été rapportés. La majorité des cas notifiés dans le cadre de la surveillance des MAPI était de manifestation systémique et de nature bénigne. Néanmoins, des cas de MAPI graves ont été notifiés. Le taux global de notification des MAPI était faible. Il est nécessaire de renforcer la surveillance de ces vaccins pour mieux organiser les stratégies visant à optimiser l'adhésion de la population burkinabé.

The Role of the European Medicines Agency in the Safety Monitoring of COVID-19 Vaccines and Future Directions in Enhancing Vaccine Safety Globally.

The European Union (EU) regulatory network was at the forefront of the safety monitoring of COVID-19 vaccines during the pandemic. An unprecedented number of case reports of suspected adverse reactions after vaccination called for huge efforts for the assessment of this safety information, to ensure that any possible risks were detected and managed as early as possible, while ruling out coincidental but temporally related adverse health outcomes. We describe the role of the European Medicines Agency alongside the EU regulatory network in the safety monitoring of the COVID-19 vaccines, and provide an insight into challenges, particularities and outcomes of the scientific assessment and regulatory decisions in the complex, dynamic international environment of the pandemic. We discuss the flexible procedural tools that were used to ensure an expedited scientific assessment of safety issues, and subsequent updates of the product information (i.e., labelling) when available evidence (e.g., spontaneous reports, findings from observational studies and/or scientific literature) suggested that causal association is at least a reasonable possibility. The safety monitoring was accompanied by enhanced transparency measures, proactive communication, and easy access to information, which played a key role in public reassurance. The pandemic has been a powerful booster for worldwide collaboration, exchange of information and work-sharing. The safety monitoring of COVID-19 vaccines continues, and the lessons learned will be applied in future safety reviews, as well as future health emergencies.

Cryptic vaccine-associated adverse events: The critical need for a new vaccine safety surveillance paradigm to improve public trust in vaccines.

Vaccination is one of the most important public health tools in the prevention of infectious diseases, and in preserving life and health. While vaccines are generally safe and usually produce only transient side effects, other types of vaccine-associated adverse events do occur. Some of these reactions are immediate and easily observable or measurable, such as swelling at the injection site or a transient fever. Others however are not immediately obvious, or are even clinically "silent" or cryptic, making them challenging to identify and link directly to a vaccine. It is critical to be vigilant about rare, silent, or subtle reactions. Public health agencies and healthcare providers can play a much more favorable and vital role in establishing vaccine trust by enlarging the current vaccine safety paradigm, and in publishing and communicating, in full, these risks and benefits transparently to the public. While there are challenges in collecting and studying cryptic adverse events characterized by subjective symptoms without biomarkers, rigorous pharmacovigilance, continued research, and high-quality study designs can assist in better understanding and addressing these concerns - and in building public trust about vaccines and vaccine safety surveillance completeness.

Safety signal detection with control of latent factors.

Postmarket drug safety database like vaccine adverse event reporting system (VAERS) collect thousands of spontaneous reports annually, with each report recording occurrences of any adverse events (AEs) and use of vaccines. We hope to identify signal vaccine-AE pairs, for which certain vaccines are statistically associated with certain adverse events (AE), using such data. Thus, the outcomes of interest are multiple AEs, which are binary outcomes and could be correlated because they might share certain latent factors; and the primary covariates are vaccines. Appropriately accounting for the complex correlation among AEs could improve the sensitivity and specificity of identifying signal vaccine-AE pairs. We propose a two-step approach in which we first estimate the shared latent factors among AEs using a working multivariate logistic regression model, and then use univariate logistic regression model to examine the vaccine-AE associations after controlling for the latent factors. Our simulation studies show that this approach outperforms current approaches in terms of sensitivity and specificity. We apply our approach in analyzing VAERS data and report our findings.

Interdisciplinary Learning Health System Response to Public Vaccine Concerns.

In Victoria, Australia, jurisdictional vaccine safety service is conducted by SAEFVIC (Surveillance of Adverse Events Following Vaccination in the Community). SAEFVIC developed a public Vaccine Safety Report (saefvic.online/vaccinesafety) to present key surveillance information. This study applies an interdisciplinary learning health system approach to evaluate the report, taking into consideration public expressions of concern on social media.

Issues with infectious disease vaccine introduction into routine vaccination in Japan, and considerations for accelerating the process.

Routine vaccinations help prevent the outbreak and spread of infectious diseases; however, it can take up to ten years from vaccine approval to introduction into routine vaccination schedules in Japan. Here, we investigate the information required to introduce an approved vaccine into routine vaccination schedules and the reasons why it takes so long. Based on the published data of the Immunization and Vaccine Committee of the Health Science Council, we set out to explore ways to facilitate discussion on this topic. The following issues were identified as discussion points: disease burden, efficacy and safety, and cost-effectiveness. Until now, epidemiological information has been used to evaluate the efficacy of vaccines, and also to evaluate the safety in the presence of notable adverse reactions. However, in some cases, it took a long time to obtain epidemiological information regarding the frequency of rare but serious adverse reactions and the need for a booster dose. Given the risk of spreading infectious diseases due to delays in decision-making, vaccines may have to be introduced into routine vaccination schedules based on the results of clinical trials that can be obtained in a relatively short period. In contrast, epidemiological information is necessary to evaluate the disease burden, frequency of adverse reactions, and the necessity of booster doses. Therefore, developing an epidemiological information collection system is urgently required.