Comparative Effectiveness of mRNA-1273 and BNT162b2 COVID-19 Vaccines Among Older Adults: Systematic Literature Review and Meta-Analysis Using the GRADE Framework.

INTRODUCTION: The mRNA vaccines mRNA-1273 and BNT162b2 demonstrated high efficacy against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in phase 3 clinical trials, including among older adults. To inform coronavirus disease 2019 (COVID-19) vaccine selection, this systematic literature review (SLR) and meta-analysis assessed the comparative effectiveness of mRNA-1273 versus BNT162b2 in older adults. METHODS: We systematically searched for relevant studies reporting COVID-19 outcomes with mRNA vaccines in older adults aged ≥ 50 years by first cross-checking relevant published SLRs. Based on the cutoff date from a previous similar SLR, we then searched the WHO COVID-19 Research Database for relevant articles published between April 9, 2022, and June 2, 2023. Outcomes of interest were SARS-CoV-2 infection, symptomatic SARS-CoV-2 infection, severe SARS-CoV-2 infection, COVID-19-related hospitalization, and COVID-19-related death following ≥ 2 vaccine doses. Random effects meta-analysis models were used to pool risk ratios (RRs) across studies. Heterogeneity was evaluated using chi-square testing. Evidence certainty was assessed per GRADE framework. RESULTS: Twenty-four non-randomized real-world studies reporting clinical outcomes with mRNA vaccines in individuals aged ≥ 50 years were included in the meta-analysis. Vaccination with mRNA-1273 was associated with significantly lower risk of SARS-CoV-2 infection (RR 0.72 [95% confidence interval (CI) 0.64‒0.80]), symptomatic SARS-CoV-2 infection (RR 0.72 [95% CI 0.62‒0.83]), severe SARS-CoV-2 infection (RR 0.67 [95% CI 0.57‒0.78]), and COVID-19-related hospitalization (RR 0.65 [95% CI 0.53‒0.79]) but not COVID-19-related death (RR 0.80 [95% CI 0.64‒1.00]) compared with BNT162b2. There was considerable heterogeneity between studies for all outcomes (I2 > 75%) except death (I2 = 0%). Multiple subgroup and sensitivity analyses excluding specific studies generally demonstrated consistent results. Certainty of evidence across outcomes was rated as low (type 3) or very low (type 4), reflecting the lack of randomized controlled trial data. CONCLUSION: Meta-analysis of 24 observational studies demonstrated significantly lower risk of asymptomatic, symptomatic, and severe infections and hospitalizations with the mRNA-1273 versus BNT162b2 vaccine in older adults aged ≥ 50 years.

New Vaccine Platforms-Novel Dimensions of Economic and Societal Value and Their Measurement.

The COVID-19 pandemic's dramatic impact has been a vivid reminder that vaccines-especially in the context of infectious respiratory viruses-provide enormous societal value, well beyond the healthcare system perspective which anchors most Health Technology Assessment (HTA) and National Immunization Technical Advisory Group (NITAG) evaluation frameworks. Furthermore, the development of modified ribonucleic acid-based (mRNA-based) and nanoparticle vaccine technologies has brought into focus several new value drivers previously absent from the discourse on vaccines as public health interventions such as increased vaccine adaptation capabilities, the improved ability to develop combination vaccines, and more efficient vaccine manufacturing and production processes. We review these novel value dimensions and discuss how they might be measured and incorporated within existing value frameworks using existing methods. To realize the full potential of next-generation vaccine platforms and ensure their widespread availability across populations and health systems, it is important that value frameworks utilized by HTAs and NITAGs properly reflect the full range of benefits for population health and well-being and cost efficiencies that these new vaccines platforms provide.

A qualitative concept elicitation study to understand patient-reported symptoms and impacts of Neisseria gonorrhoeae infections in the United States.

BACKGROUND: Gonorrhea is the second most common bacterial sexually-transmitted infection in the United States (US), with rising rates. Emerging antimicrobial resistance threatens public health; and vaccines are in development. This study documents patient-reported gonorrhea symptoms and health-related quality of life (HRQoL) impact, in women who have sex with men (WSM), men who have sex with women (MSW) and men who have sex with men (MSM). METHODS: Semi-structured qualitative interviews were conducted (April 2021-March 2022) among US adults with recent (≤6 months) confirmed gonorrhea. Concept saturation was achieved, confirming adequate participant numbers to meet objectives. Elicited symptom and HRQoL impacts were used to develop a conceptual disease model. Common patient-reported outcome measure (PROM) items were compared to elicited concepts. RESULTS: 32 participants (15 WSM, 8 MSW and 9 MSM) were included. Eight were asymptomatic; six had repeat infections; five women and four men had complications (i.e., infertility or pelvic inflammatory disease [PID], and urethritis, respectively).The most frequently reported symptoms were vaginal discharge (n = 11/12), dysuria (n = 10/12), and abdominal/vaginal pain (n = 9/12) for symptomatic WSM; dysuria (n = 5/6) and penile discharge (n = 4/6) for symptomatic MSW; and throat, testicular or rectal pain (n = 4/6) for symptomatic MSM. All (symptomatic and asymptomatic) participants reported HRQoL impacts including negative emotional experiences (n = 31/32), and interference with sexual activity (n = 30/32), relationships (n = 24/32) and social life (n = 17/32). Concepts were poorly represented in existing PROMs. CONCLUSION: Participants reported a diverse range of symptoms and HRQoL impacts, to help inform the value of new treatment and prevention options. More research is needed to quantify patient burden and develop PROMs.

Lifecycle model-based evaluation of infant 4CMenB vaccination in the UK.

OBJECTIVES: Invasive meningococcal disease, an uncommon but severe disease, imposes catastrophic health and economic burdens. Cost-utility analysis (CUA) assumes separability in lifetime health and economic variables and cannot capture the full value of preventing such burdens. We overcome these limitations with a retrospective societal perspective cost-benefit analysis (CBA) of meningococcal serogroup B vaccination (4CMenB) of one infant cohort in the United Kingdom using a health-augmented lifecycle model (HALM) incorporating health's interactions with consumption, earnings, non-market time and financial risk. METHODS: We used a static Markov model of vaccination's health impact and an HALM to estimate the private willingness to pay (PWTP) for the intrinsic and instrumental value of health under perfect capital markets, financial risk protection in the absence of insurance against permanent disability, parental spillovers, and acute phase disability. We estimated social WTP (SWTP) incorporating social severity preferences. We estimated rates of return that inform health payer reimbursement decisions, finance ministry budgeting decisions, and legislature taxation decisions. An expert Advisory Board investigated the validity of applying the HALM to infant 4CMenB. RESULTS: The PWTP for a 2 + 1 vaccination schedule is £395, comprising £166 of disability insurance value, £79 of positive parental spillover value, £28 in the value of averting acute phase disability, and £122 in residual intrinsic and instrumental value of health. SWTP is £969. CONCLUSIONS: HALM-based CBA provides an empirically richer, more utility-theoretically grounded approach to vaccine evaluation than CUA, demonstrating good value for money for legislatures (based on private values) and for all decision-makers (based on social values).

Clinical impact and cost-effectiveness of the updated COVID-19 mRNA Autumn 2023 vaccines in Germany.

OBJECTIVES: To assess the potential clinical impact and cost-effectiveness of coronavirus disease 2019 (COVID-19) mRNA vaccines updated for Autumn 2023 in adults aged ≥60 years and high-risk persons aged 30-59 years in Germany over a 1-year analytic time horizon (September 2023-August 2024). METHODS: A compartmental Susceptible-Exposed-Infected-Recovered model was updated and adapted to the German market. Numbers of symptomatic infections, a number of COVID-19 related hospitalizations and deaths, costs, and quality-adjusted life-years (QALYs) gained were calculated using a decision tree model. The incremental cost-effectiveness ratio of an Autumn 2023 Moderna updated COVID-19 (mRNA-1273.815) vaccine was compared to no additional vaccination. Potential differences between the mRNA-1273.815 and the Autumn Pfizer-BioNTech updated COVID-19 (XBB.1.5 BNT162b2) vaccines, as well as societal return on investment for the mRNA-1273.815 vaccine relative to no vaccination, were also examined. RESULTS: Compared to no autumn vaccination, the mRNA-1273.815 campaign is predicted to prevent approximately 1,697,900 symptomatic infections, 85,400 hospitalizations, and 4,100 deaths. Compared to an XBB.1.5 BNT162b2 campaign, the mRNA-1273.815 campaign is also predicted to prevent approximately 90,100 symptomatic infections, 3,500 hospitalizations, and 160 deaths. Across both analyses we found the mRNA-1273.815 campaign to be dominant. CONCLUSIONS: The mRNA-1273.815 vaccine can be considered cost-effective relative to the XBB.1.5 BNT162b2 vaccine and highly likely to provide more benefits and save costs compared to no vaccine in Germany, and to offer high societal return on investment.

The potential clinical impact and cost-effectiveness of the updated COVID-19 mRNA fall 2023 vaccines in the United States.

AIMS: To assess the potential clinical impact and cost-effectiveness of COVID-19 mRNA vaccines updated for fall 2023 in adults aged ≥18 years over a 1-year analytic time horizon (September 2023-August 2024). MATERIALS AND METHODS: A compartmental Susceptible-Exposed-Infected-Recovered model was updated to reflect COVID-19 cases in summer 2023. The numbers of symptomatic infections, COVID-19-related hospitalizations and deaths, and costs and quality-adjusted life-years (QALYs) gained were calculated using a decision tree model. The incremental cost-effectiveness ratio (ICER) of a Moderna updated mRNA fall 2023 vaccine (Moderna Fall Campaign) was compared to no additional vaccination. Potential differences between the Moderna and the Pfizer-BioNTech fall 2023 vaccines were also examined. RESULTS: Base case results suggest that the Moderna Fall Campaign would decrease the expected 64.2 million symptomatic infections by 7.2 million (11%) to 57.0 million. COVID-19-related hospitalizations and deaths are expected to decline by 343,000 (-29%) and 50,500 (-33%), respectively. The Moderna Fall Campaign would increase QALYs by 740,880 and healthcare costs by $5.7 billion relative to no vaccine, yielding an ICER of $7700 per QALY gained. Using a societal cost perspective, the ICER is $2100. Sensitivity analyses suggest that vaccine effectiveness, COVID-19 incidence, hospitalization rates, and costs drive cost-effectiveness. With a relative vaccine effectiveness of 5.1% for infection and 9.8% for hospitalization for the Moderna vaccine versus the Pfizer-BioNTech vaccine, use of the Moderna vaccine is expected to prevent 24,000 more hospitalizations and 3300 more deaths than the Pfizer-BioNTech vaccine. LIMITATIONS AND CONCLUSIONS: As COVID-19 becomes endemic, future incidence, including patterns of infection, are highly uncertain. The effectiveness of fall 2023 vaccines is unknown, and it is unclear when a new variant that evades natural or vaccine immunity will emerge. Despite these limitations, our model predicts the Moderna Fall Campaign vaccine is highly cost-effective across all sensitivity analyses.

The potential public health impact of adolescent 4CMenB vaccination on Neisseria gonorrhoeae infection in England: a modelling study.

INTRODUCTION: Diagnoses of gonorrhoea in England rose by 26% between 2018 and 2019. Recent evidence that a vaccine against meningococcal B disease currently offered to infants in the UK (4CMenB) could additionally protect (with 31% efficacy) against gonorrhoea has led to renewed hope for a vaccine. A Phase 2 proof-of-concept trial of 4CMenB vaccination against gonorrhoea in adults is currently underway. OBJECTIVES: To investigate the potential public health impact of adolescent gonorrhoea vaccination in England, considering different implementation strategies. METHODS: We developed a deterministic transmission-dynamic model of gonorrhoea infection among heterosexual 13-64-year-olds stratified by age, sex and sexual activity. We explored the impact of a National Immunisation Programme (NIP) among 14-year-olds for a vaccine with 31% efficacy, 6 years' duration of protection, and 85% uptake. We also explored how impact might change for varying efficacy (20-50%) and uptake (75-95%), the addition of a catch-up programme, the use of boosters, and varying duration of protection. RESULTS: An NIP against gonorrhoea could lead to 50,000 (95% credible interval, CrI 31,000-80,000) and 849,000 (95%CrI 476,000-1,568,000) gonorrhoea infections being averted over 10 and 70 years, respectively, in England, for a vaccine with 31% efficacy and 85% uptake. This is equivalent to 25% (95%CrI 17-33%) of heterosexual infections being averted over 70 years. Vaccine impact is predicted to increase over time and be greatest among 13-18-year-olds (39% of infections 95%CrI 31-49% averted) over 70 years. Varying vaccine efficacy and duration of protection had a noticeable effect on impact. Catch-up and booster vaccination increased the short- and long-term impact, respectively. CONCLUSIONS: A partially-effective vaccine against gonorrhoea infection, delivered to 14-year-olds alongside the MenACWY vaccine, could have an important population impact on gonorrhoea. Catch-up and booster vaccination could be considered alongside cohort vaccination to increase impact.

Capturing the value of vaccination: impact of vaccine-preventable disease on hospitalization.

Evidence from epidemiological studies suggests that vaccine-preventable disease (VPD) such as influenza or herpes zoster contribute significantly to the increased risk of older adults for cardiovascular, cerebrovascular, neurological, and renal complications in the period after illnesses. However, since the period of elevated risk can persist well beyond the duration of the acute illness, the connection is not always recognized. To obtain insights into the relationship between diagnoses for vaccine-preventable disease and for other conditions, we analyzed principal and secondary diagnoses for 3,127,768 inpatient admissions of adults 50 years and older in the United States, using medical insurance claims drawn from the IBM® MarketScan® Research Databases (Marketscan). The Marketscan data indicated that overall, 3.1% of these hospitalizations had a principal diagnosis of VPD with variation by month of admission, and age. However, hospitalizations with a principal non-VPD diagnosis but secondary VPD diagnoses were 2.8 times more frequent, with particularly high rates in those whose principal diagnoses were non-VPD respiratory or circulatory disease. Hospitalized patients with a secondary VPD diagnosis tended to have poorer discharge outcomes, and longer length of stay in comparison to hospitalized patients without a secondary VPD diagnosis. In total, these data are consistent with suggestions that VPDs play a significant and potentially under-estimated role in hospitalization and outcomes, which may be potentially preventable by improved vaccination coverage.

Capturing the value of vaccination within health technology assessment and health economics: Literature review and novel conceptual framework.

BACKGROUND: Vaccination provides significant health gains to individuals and society and can potentially improve health equity, healthcare systems and national economies. Policy decisions, however, are rarely informed by comprehensive economic evaluations (EE) including vaccination's wide-ranging value. The objective of this analysis was to focus on health technology assessment systems to identify relevant value concepts in order to improve current EE of non-pandemic vaccines. METHODS: Following a literature review, a novel Value of Vaccination (VoV) framework was developed with experts in vaccine EE from developed countries with established health technology assessment systems. RESULTS: Forty-four studies presenting value frameworks or concepts applicable to vaccination were included. Eighteen unique value concepts relevant to EE were identified and defined. These were categorised within the VoV framework using three dimensions, moving from a narrow payer perspective to a more expansive and societal perspective. The dimensions were: (I) conventional payer perspective concepts (e.g., health gains in vaccinees, direct medical costs); (II) conventional societal perspective concepts (e.g., indirect health/economic gains to caregivers/households, productivity in vaccinees); and (III) novel societal concepts (e.g., financial risk protection, peace of mind, societal health gains, healthcare systems security, political stability, social equity and macroeconomic gains). While good quality evidence and methods are available to support concepts in Dimensions I and II, further work is needed to generate the required evidence for vaccination impact on Dimension III concepts. CONCLUSIONS: The devastating effect on nations of the COVID-19 pandemic has helped to highlight the potential far-reaching benefits that many vaccination programmes can offer. This VoV framework is particularly relevant to policy decisions considering EE, and the potential future expansion of non-pandemic vaccination value considerations. The framework helps to understand and compare current value considerations across countries and payer versus societal perspectives. It provides decision-makers with a transparent and logical path to broaden consideration of VoV in EE.

Capturing the value of vaccination within health technology assessment and health economics: Country analysis and priority value concepts.

BACKGROUND: A value of vaccination framework for economic evaluation (EE) identified unique value concepts for the broad benefits vaccination provides to individuals, society, healthcare systems and national economies. The objectives of this paper were to work with experts in developed countries to objectively identify three priority concepts to extend current EE. METHODS: The previously developed classification of value concepts in vaccination distinguished 18 concepts, categorised as conventional payer and societal perspective concepts and novel broader societal concepts. Their inclusion in current EE guidelines was assessed. Experts identified eight criteria relevant to decision-making and measurement feasibility, which were weighted and used to score each concept. The relative ranking of concepts by importance and the gaps in guidelines were used to identify three priority concepts on which to focus immediate efforts to extend EE. RESULTS: The EE guidelines review highlighted differences across countries and between guidelines and practice. Conventional payer perspective concepts (e.g., individual and societal health gains and medical costs) were generally included, while gaps were evident for conventional societal perspective concepts (e.g., family/caregiver health and economic gains). Few novel broader societal benefits were considered, and only in ad hoc cases. The top-three concepts for near-term consideration: macroeconomic gains (e.g., benefiting the economy, tourism), social equity and ethics (e.g., equal distribution of health outcomes, reduced health/financial equity gaps) and health systems strengthening, resilience and security (e.g., efficiency gains, reduced disruption, increased capacity). CONCLUSIONS: Gaps, inconsistencies and limited assessment of vaccination value in EE can lead to differences in policy and vaccination access. The three priority concepts identified provide a feasible approach for capturing VoV more broadly in the near-term. Robust methods for measuring and valuing these concepts in future assessments will help strengthen the evidence used to inform decisions, improving access to vaccines that are demonstrably good value for money from society's point of view.

Care pathways in invasive meningococcal disease: a retrospective analysis of the French national public health insurance database.

Invasive meningococcal disease (IMD) carries a high burden in terms of mortality, long-term complications, and cost, which can be significantly reduced by vaccination. The objectives of this case-control study were to document the care pathways of patients with IMD before, during, and after hospitalization and to assess in-hospital complications and long-term sequelae. Cases consisted of all people hospitalized for IMD in France between 2012 and 2017. Controls were matched by age, gender, and district of residence. Data were extracted from the French national public health insurance database on demographics, hospitalizations, mortality and potential sequelae of IMD. Overall, 3,532 cases and 10,590 controls were assessed and followed up for 2.8 years (median). During hospitalization, 1,577 cases (44.6%) stayed in an intensive care unit, 1,238 (35.1%) required mechanical ventilation, and 43 (1.2%) underwent amputation; 293 cases (8.3%) died in hospital and a further 163 (4.6%) died following discharge; 823 cases (25.4% of survivors) presented ≥1 sequela and 298 (9.2%) presented multiple sequelae. The most frequently documented sequelae were epilepsy (N = 205; 5.8%), anxiety (N = 196; 5.5%), and severe neurological disorders (N = 193; 5.5%). All individual sequelae were significantly more frequent (p < .0001) in cases than controls. Hearing/visual impairment and communication problems were conditions that presented the highest risk for cases compared to controls (risk ratios >20 in all cases). In conclusion, this study highlights the importance of providing optimal medical care for patients with IMD, of minimizing the delay before hospitalization, and of effective prevention through comprehensive vaccination programs.

Benefits of providing optimal medical care for IMD patients.Importance of minimising the delay before hospitalization.IMD remains challenging to diagnose, and vaccination is the most efficient way to prevent the disease and its complications.

Country score tool to assess readiness and guide evidence generation of immunization programs in aging adults in Europe.

Objectives: Delaying of policies for immunization of aging adults, low vaccine uptake, and the lack of supportive evidence at the national level could diminish the value in health and economics of such programs. This study aims to develop a "country score tool" to assess readiness and to facilitate evidence generation for aging adult immunization programs in Europe, and examine the comprehensiveness, relevance, acceptability, and feasibility of the tool. Methods: The tool was developed in two phases. First, a modified Delphi process was used to construct the tool. The process included a literature review, stakeholder consultations, and a three-round Delphi study. The Delphi panel included researchers, supra-national and national decision-makers of immunization programs recruited from five countries, using snowball sampling method. The consensus was predefined at the agreement rate of 70%. Pilot testing of the tool was conducted in the Netherlands, Germany, Serbia, and Hungary involving researchers in the field of health technology assessment. After assessing the countries' readiness, researchers evaluated four features, namely comprehensiveness, relevance, acceptability, and feasibility of the tool via an online survey that included 5-scale Likert questions. The percentages of affirmative answers including "agree" and "totally agree" choices were presented. Results: The review identified 16 tools and frameworks that formed the first version of our tool with 14 items. Eight experts were involved in the Delphi panel. Through three Delphi rounds, four items were added, one was dropped, and all others were amended. The consensus was achieved on the tool with 17 items divided into decision-making and implementation parts. Each item has a guiding question, corresponding to explanations and rationales to inform assessment with readiness scores. Eight researchers completed the pilot testing. The tool was rated as comprehensive (75%), relevant (100%), acceptable (75%), and feasible (88%) by participants. Conclusion: Through a thorough and transparent process, a country score tool was developed helping to identify strengths, weaknesses, and evidential requirements for decision-making and implementation of immunization programs of aging adults. The tool is relevant for different European contexts and shows good comprehensiveness, acceptability, and feasibility.

Long-Term Mortality and State Financial Support in Invasive Meningococcal Disease-Real-World Data Analysis Using the French National Claims Database (SNIIRAM).

OBJECTIVES: Invasive meningococcal disease (IMD) is an uncommon disease known for its acute phase mortality and long-term sequelae. The objective was to assess the impact of IMD on post-discharge mortality risk and dependence on the French state for financial aid. METHODS: A 6-year retrospective analysis in the national insurance database (SNIIRAM) assessed mortality in IMD cases (both during acute phase and post-discharge) and matched controls as well as benefit claims (i.e., for salary loss compensation [SLC], long-term sickness [ALD] and complementary health insurance [CMUc]). Observed survival data were extrapolated to estimate lifetime life expectancy following IMD. RESULTS: Between 2012 and 2017, 3532 incident IMD cases were hospitalised in France (peak in < 2 years and 15-24 year olds), of which 23.3% developed sequelae. With an average follow-up of 2.8 years, 12.9% of cases vs. 3.2% of controls died (p < 0.0001), with significantly more cases than controls dying both during the acute phase and post-discharge. Around a third of these deaths occurred post-discharge. Extrapolation to lifetime life expectancy estimated that having IMD at any age significantly reduces life expectancy in survivors of the acute disease phase, e.g., by around 16 years for cases aged 0-50 years. IMD cases in France were significantly more likely to receive state-funded SLC (relative risk [RR] 3.9, 95% confidence interval [95% CI] 2.3-6.4) and ALD benefits (RR 1.85, 95% CI 1.71-2.00). CONCLUSIONS: IMD has a significant impact on mortality post-discharge, expected to persist over a lifetime. In addition to long-term sequelae, the financial burden extends beyond the healthcare sector. These results highlight the importance of IMD prevention (e.g., vaccination).

Invasive meningococcal disease (IMD) is an uncommon disease mainly affecting children, with severe consequences such as a risk of dying within hours of symptoms and a risk of developing long-term conditions affecting health, learning and ability to work. Little is known of the risk of dying in survivors after discharge from hospital or of survivors' financial support needs. The French national insurance claims database (SNIIRAM) was reviewed for data on IMD patients hospitalised between 2012 and 2017 and matched controls without IMD. Data, available following IMD hospitalisation for an average of around 3 years, were extrapolated to estimate the lifelong impact of the disease. Among 3532 hospitalised IMD cases, the study found that nearly 13% died, of which a third of deaths occurred post-discharge. The cases who survived the acute disease phase were also more likely to require government funds because of loss of salary or to cover long-term healthcare costs. In addition to the well-known acute phase burden of IMD, this study has shown that there is a long-term effect on risk of dying and on need for government support. This demonstrates the importance of prevention, for example, by vaccination.

Public Health Impact and Cost-Effectiveness Analysis of Routine Infant 4CMenB Vaccination in Germany to Prevent Serogroup B Invasive Meningococcal Disease.

INTRODUCTION: Invasive meningococcal disease (IMD) is an uncommon, severe, life-threatening disease primarily affecting infants, with potential lifelong sequelae. Neisseria meningitidis (Nm) serogroup B (MenB) causes most IMD cases in Germany, many of which can be prevented with four-component MenB (4CMenB) vaccination. The potential public health and economic impact of introducing routine 4CMenB infant vaccination in Germany was assessed. METHODS: A dynamic transmission-based cost-effectiveness model adapted for Germany assessed the impact of infant 4CMenB universal mass vaccination (UMV) versus no vaccination. The model included the latest real-world evidence on vaccine effectiveness, the comprehensive burden of disease on patients (sequelae) and their family (quality of life impact), comprehensive German IMD costs, and vaccination uptake assumptions. RESULTS: The largest public health impact was predicted in children: a rapid decline, 5 years after UMV implementation, of 39.9% (34.7%) for MenB (all IMD) cases aged 0-4 years and 42.4% (36.8%) in infants. Over lifetime (100-year time horizon), 4CMenB could prevent 3154 MenB (3303 all IMD) cases, 291 MenB (304 all IMD) deaths and 1370 MenB (1435 all IMD) long-term sequelae. 4CMenB saved 25,878 quality-adjusted life-years (QALYs), at a cost of €188,762 per QALY gained in the base case (societal perspective including lost productivity). Scenarios including potential Nm carriage protection (enabling herd protection) or societal preferences for the prevention of severe diseases led to more cost-effective results, while a scenario excluding IMD impact beyond the patient with increased discounting of vaccination health benefits produced less cost-effective results. CONCLUSIONS: MenB IMD is a vaccine-preventable disease. This analysis for Germany can inform decision-makers on the potential impact of introducing infant 4CMenB UMV. The program is predicted to rapidly produce health benefits (reduction in child cases, deaths and sequelae) at a cost per QALY to society of around €190,000 (base case), decreasing to around €78,000 when considering societal preferences and IMD underreporting.

Invasive meningococcal disease (IMD) is an uncommon but severe infection, usually presenting as meningitis and/or sepsis, caused by the bacteria Neisseria meningitidis. Most cases occur in infants, young children and adolescents. Patients who survive the disease can develop lifelong sequelae, such as physical, neurological and psychological/behavioural problems that impact their quality of life and that of their family/caregivers. This disease can be prevented by vaccination. The use of the four-component meningococcal serogroup B vaccine (4CMenB) in countries like Germany can prevent the most common form of this disease, IMD caused by serogroup B. This study assessed the public health and economic impact of infant vaccination in Germany with 4CMenB. For this, the authors used an economic model that measured the lifetime impact of the disease on patients but also on their families. The model predicted that after 5 years of vaccination, the number of cases and deaths in infants and young children aged 0­4 years would rapidly decrease by almost 40%. Over a long-term horizon of 100 years, this number was predicted to remain stable. Due to the reduced number of cases, vaccination would also result in fewer deaths and patients with sequelae, as well as cost savings for the healthcare system and society due to the reduced loss of productivity. In conclusion, in Germany, IMD caused by serogroup B is preventable through vaccination, and the 4CMenB vaccine in German infants is predicted to rapidly reduce the disease burden, save lives and prevent healthcare costs.

Applying a novel approach to scoping review incorporating artificial intelligence: mapping the natural history of gonorrhoea.

BACKGROUND: Systematic and scoping literature searches are increasingly resource intensive. We present the results of a scoping review which combines the use of a novel artificial-intelligence-(AI)-assisted Medline search tool with two other 'traditional' literature search methods. We illustrate this novel approach with a case study to identify and map the range of conditions (clinical presentations, complications, coinfections and health problems) associated with gonorrhoea infection. METHODS: To fully characterize the range of health outcomes associated with gonorrhoea, we combined a high yield preliminary search with a traditional systematic search, then supplemented with the output of a novel AI-assisted Medline search tool based on natural language processing methods to identify eligible literature. RESULTS: We identified 189 health conditions associated with gonorrhoea infection of which: 53 were identified through the initial 'high yield' search; 99 through the systematic search; and 124 through the AI-assisted search. These were extracted from 107 unique references and 21 International Statistical Classification of Diseases and Related Health Problems Ninth and Tenth Revision (ICD 9/10) or Read codes. Health conditions were mapped to the urogenital tract (n = 86), anorectal tract (n = 6) oropharyngeal tract (n = 5) and the eye (n = 14); and other conditions such as systemic (n = 61) and neonatal conditions (n = 7), psychosocial associations (n = 3), and co-infections (n = 7). The 107 unique references attained a Scottish Intercollegiate Guidelines Network (SIGN) score of ≥2++ (n = 2), 2+ (14 [13%]), 2- (30 [28%]) and 3 (45 [42%]), respectively. The remaining papers (n = 16) were reviews. CONCLUSIONS: Through AI screening of Medline, we captured - titles, abstracts, case reports and case series related to rare but serious health conditions related to gonorrhoea infection. These outcomes might otherwise have been missed during a systematic search. The AI-assisted search provided a useful addition to traditional/manual literature searches especially when rapid results are required in an exploratory setting.

Vaccine market access pathways in the EU27 and the United Kingdom - analysis and recommendations for improvements.

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

Systematic Literature Review and Quantitative Analysis of Health Problems Associated with Sexually Transmitted Neisseria gonorrhoeae Infection.

OBJECTIVE: Neisseria gonorrhoeae (Ng) is the second most common sexually transmitted bacterial infection (STI), leading to serious health problems in men, women and newborns. While early antibiotic treatment is effective, infections are increasingly antibiotic-resistant. No systematic reviews present health problems associated with Ng infections or their likelihood of occurrence. The objective, therefore, was to conduct a systematic literature review to address these gaps. METHODS: A systematic literature review was conducted of all studies with an English abstract published since 1950 (Pubmed)/1966 (Embase). The search included patients with a history of/current sexually transmitted Ng infection. Expected outcomes were defined from published reviews of gonorrhoea health problems. Observational studies with a control group were included. A decision tree determined the best quality studies for each outcome, prioritising generalisable populations, laboratory-confirmed diagnosis, clearly defined outcomes, no STI co-infections, adjusted analyses and risk estimates. Where feasible, a meta-analysis was performed; otherwise, the best quality study estimates were identified. FINDINGS: In total, 46 studies were included, and 22 health problems were identified. Of these problems, Ng infection was statistically significantly associated with preterm premature ruptures of membranes, preterm birth, low birth weight, stillbirth, infant death, neonatal ophthalmia, schizophrenia in offspring, pelvic inflammatory disease and subsequent tubal infertility, human immunodeficiency virus and prostate cancer/problems. High-quality evidence was generally lacking, with high heterogeneity across studies, and limited or inconclusive data on other health problems. CONCLUSION: Ng infection is associated with severe health problems in women, men and newborns. More high-quality comparative studies are needed to address the limitations in current knowledge.