Introduction & Objective: Older adults and adults with comorbidities, such as metabolic diseases, are at increased risk of severe respiratory syncytial virus (RSV) disease. This study assessed the cost-effectiveness of adjuvanted RSVPreF3 vaccination in adults 50-59 years of age (YOA) with diabetes in the US. Methods: A Markov model was used to estimate costs and health outcomes over a 3-year time horizon from a societal perspective, comparing scenarios with and without one-time adjuvanted RSVPreF3 vaccination. Indirect costs and quality-adjusted life year (QALY) losses due to RSV-related death were modeled over the remaining lifetime. The population included 5,617,227 US adults 50-59 YOA with diabetes. Vaccination coverage of 50.1% was assumed, based on influenza vaccination coverage. Scientific literature and public sources were used to inform model inputs. Incremental cost and health outcomes were reported along with the incremental cost-effectiveness ratio (ICER), comparing adjuvanted RSVPreF3 vaccination to no vaccination. Results: Over the 3-year time horizon, adjuvanted RSVPreF3 vaccination avoided an estimated 180,546 symptomatic RSV acute respiratory illnesses, including 144,676 lower respiratory tract disease cases, 108,392 RSV-related outpatient visits, and 7,841 RSV-related hospitalizations. Vaccination resulted in incremental total societal costs of -$39 million (M), including incremental direct and indirect costs of $623M and -$662M, respectively. Adjuvanted RSVPreF3 vaccination avoided 10,290 QALY losses and 551 RSV-related deaths. With improved health outcomes and lower societal costs, adjuvanted RSVPreF3 vaccination was dominant versus no vaccination (ICER <$0 per QALY gained). Conclusion: One-time adjuvanted RSVPreF3 vaccination resulted in improved health outcomes and reduced societal costs compared to no vaccination, suggesting it is cost-effective for the prevention of RSV in adults 50-59 YOA with diabetes. D. Singer: Employee; GlaxoSmithKline plc. Stock/Shareholder; GlaxoSmithKline plc. E. La: Employee; GlaxoSmithKline plc. Stock/Shareholder; GlaxoSmithKline plc. J. Graham: Research Support; GlaxoSmithKline plc. M. Grace: None. S. Poston: Employee; GlaxoSmithKline plc. D. Molnar: Employee; GlaxoSmithKline plc. GlaxoSmithKline Biologicals SA (VEO-000556)

Respiratory syncytial virus (RSV) is an important cause of lower respiratory tract disease in older adults, resulting in substantial morbidity and mortality. This study estimates the public health impact of vaccination with the adjuvanted RSVPreF3 vaccine among adults aged ≥ 60 years in the United States (US). A static, multi-cohort Markov model was used to estimate RSV-related outcomes over a 3-year time horizon for scenarios with and without one-time RSV vaccination. The base-case analysis assumed the same vaccination coverage as for influenza vaccines, with key epidemiology and vaccine inputs obtained from the published literature and phase 3 clinical trial results for the adjuvanted RSVPreF3 vaccine. Model outcomes included the clinical burden of RSV (symptomatic RSV acute respiratory illness [RSV-ARI] cases [classified as upper or lower respiratory tract disease], pneumonia complications, and mortality) and RSV-related healthcare resource use (hospitalizations, emergency department visits, outpatient visits, and antibiotic prescriptions). In the base-case analysis, approximately 56.7 million adults aged ≥ 60 years received the vaccine, resulting in 2,954,465 fewer symptomatic RSV-ARI cases over 3 years compared with no vaccination, including 321,019 fewer X-ray confirmed pneumonia cases and 16,660 fewer RSV-related deaths. Vaccination also prevented a substantial number of RSV-related hospitalizations (203,891), emergency department visits (164,060), outpatient visits (1,577,586), and antibiotic prescriptions (1,343,915) over the 3-year period. A considerable public health impact was observed across a range of sensitivity analyses. These findings highlight the potential of the adjuvanted RSVPreF3 vaccine to substantially reduce RSV disease burden among US older adults aged ≥ 60 years.

Respiratory syncytial virus (RSV) is a common cause of acute respiratory illness in individuals of all ages, with adults aged ≥60 years and adults with certain chronic conditions at increased risk of severe RSV-related outcomes. This study evaluates the cost-effectiveness of the adjuvanted RSVPreF3 vaccine versus no vaccine in adults aged ≥60 years in the United States (US). A multi-cohort Markov model was developed with a 5-year time horizon and 1-month cycle length to compare outcomes for no vaccination and one-time adjuvanted RSVPreF3 vaccination (assuming the same vaccination as for influenza vaccines). Clinical parameters (e.g., vaccine efficacy) were based on phase 3 clinical trial data over 3 seasons, with all other inputs obtained from public US sources and scientific literature. Outcomes included total and incremental quality-adjusted life year (QALY) losses and costs, as well as incremental cost-effectiveness ratios (ICERs). Sensitivity analyses were conducted to evaluate the sensitivity of results to inputs. In the base case, the model estimated that vaccinating 52.7 million adults aged ≥60 years with the adjuvanted RSVPreF3 vaccine once would result in 244,424 fewer QALY losses and an incremental societal cost of $4.5 billion over 5 years, with vaccination costs partially offset by reduced disease-related costs. From the societal perspective, adjuvanted RSVPreF3 vaccination resulted in an ICER of $18,430 per QALY gained. Results were relatively robust across sensitivity analyses and indicate that adjuvanted RSVPreF3 vaccination is a cost-effective option for the prevention of RSV in US adults aged ≥ 60 years, reducing the substantial burden within this population.

BACKGROUND:Respiratory syncytial virus (RSV), a common respiratory pathogen, can lead to severe symptoms, especially in older adults (OA). A recently developed RSV prefusion F protein (RSVPreF3 OA) vaccine confers high protection against RSV lower respiratory tract disease (LRTD) over two full RSV seasons. The aim of this study was to assess the potential public health impact of RSVPreF3 OA vaccination in the Japanese OA population. RESEARCH DESIGN AND METHODS:A static Markov model was used to estimate the number of symptomatic RSV cases, hospitalizations and deaths in the Japanese population aged ≥ 60 years over a 3-year time horizon. Japan-specific RSV epidemiology and healthcare resource use parameters were used; vaccine efficacy was derived from a phase 3 randomized study (AReSVi-006, NCT04886596). Vaccination coverage was set to 50%. RESULTS:Without vaccination, >5 million RSV acute respiratory illness (ARI) would occur (2.5 million LRTD and 2.8 million upper respiratory tract infections) leading to ~ 3.5 million outpatient visits, >534,000 hospitalizations and ~ 25,500 RSV-related deaths over 3 years. Vaccination could prevent > 1 million RSV-ARI cases, 728,000 outpatient visits, 143,000 hospitalizations and 6,840 RSV-related deaths. CONCLUSIONS:RSVPreF3 OA vaccination is projected to have a substantial public health impact by reducing RSV-related morbidity and mortality in the OA population.

Background: Respiratory syncytial virus (RSV) is a leading cause of acute respiratory illness, with severe outcomes in older adults. Information on the prevalence, hospitalization rate, and impact on the health-related quality of life (HRQoL) of RSV in older adults with acute respiratory infections (ARI) in outpatient settings in Japan is limited. Methods: This multi-center epidemiological study included outpatients aged >= 60 years presenting with ARI between August 2021 and February 2023. Nasal and throat swabs were collected and tested by reverse transcription polymerase chain reaction (RT-PCR). The prevalence of RT-PCR-confirmed RSV (cRSV)-ARI, cRSVlower respiratory tract disease (LRTD), and other respiratory viruses was calculated by season, region, age group, and RSV subtype. HRQoL was assessed via patient-reported outcomes. Results: The study included 923 ARI episodes (cRSV-ARI: N = 24; non-cRSV-ARI: N = 899). In years 1 and 2 (August 2021-July 2022 and August 2022-February 2023), the prevalence of cRSV-ARI was 2.5% and 2.8%, respectively. There was a predominance of RSV-B and RSV-A subtypes in years 1 and 2, respectively. In years 1 and 2 combined, 37.5% of cRSV-ARI cases had lower respiratory tract infection; all cRSV-LRTD cases occurred in those aged 60-74 years. RSV-ARI cases reported throat, chest, and respiratory symptoms, leading to impaired functioning and HRQoL. Conclusions: During the observed study period, RSV was circulating among older adults in Japan. RSV was a leading cause of ARI and LRTD. More data are needed to fully clarify the burden of RSV among older adults in Japan.

ObjectivesOlder adults (OA) are at risk of morbidity and mortality from respiratory syncytial virus (RSV), a major cause of seasonal acute respiratory illness. The first RSV vaccine for OA (RSVPreF3 OA) was recently launched in Japan. With the already large and growing OA population in Japan, and limited RSV treatments, prevention is key. The aim of this study was to assess the cost-effectiveness of introducing RSVPreF3 OA for Japanese adults aged >= 60 years.MethodsA static multicohort Markov model was adapted to assess the cost-effectiveness of a single dose of RSVPreF3 OA versus no vaccination over a three-year time horizon. Deterministic and probabilistic sensitivity analyses were conducted to assess parameter uncertainty.ResultsRSVPreF3 OA vaccination prevented 1,008,499 cases and 6,840 deaths, with 109,119 quality-adjusted life-years (QALYs) gained. The incremental cost-effectiveness ratio was Japanese yen (JPY) 4,180,084/QALY gained from a payer perspective and JPY 4,041,917/QALY gained from a societal perspective (with productivity loss from RSV disease), thus vaccination was considered cost-effective. Base case results were robust to changes in sensitivity and scenario analyses.ConclusionsRSVPreF3 OA vaccination for adults >= 60 years can provide substantial health benefits and is a cost-effective intervention to reduce the RSV burden in Japan.

Background:Respiratory syncytial virus (RSV) is a contagious pathogen causing acute respiratory infections (ARIs). Symptoms range from mild upper respiratory tract infections to potentially life-threatening lower respiratory tract disease (LRTD). In adults ≥60 years old, vaccine efficacy of a candidate vaccine for older adults (RSVPreF3 OA) was 71.7% against RSV-ARI and 82.6% against RSV-LRTD (AReSVi-006/NCT04886596). We present the patient-reported outcomes (PROs) from the same trial at the end of the first RSV season in the northern hemisphere (April 2022). Methods:In this phase 3 trial, adults aged ≥60 years were randomized (1:1) to receive one dose of RSVPreF3 OA vaccine or placebo. PROs were assessed using InFLUenza Patient-Reported Outcome (FLU-PRO), Short Form-12 (SF-12), and EuroQol-5 Dimension (EQ-5D) questionnaires. Peak FLU-PRO Chest/Respiratory scores during the first 7 days from ARI episode onset were compared using a Wilcoxon test. Least squares mean (LSMean) of SF-12 physical functioning (PF) and EQ-5D health utility scores were estimated using mixed effects models. Results:In the RSVPreF3 OA group (N = 12,466), 27 first RSV-ARI episodes were observed versus 95 in the Placebo group (N = 12,494). Median peak FLU-PRO Chest/Respiratory scores were lower in RSVPreF3 OA (1.07) versus Placebo group (1.86); p = 0.0258. LSMean group differences for the PF and EQ-5D health utility score were 7.00 (95% confidence interval [CI]: -9.86, 23.85; p = 0.4125) and 0.0786 (95% CI: -0.0340, 0.1913; p = 0.1695). Conclusions:The RSVPreF3 OA vaccine, in addition to preventing infection, attenuated the severity of RSV-associated symptoms in breakthrough infections, with trends of reduced impact on PF and health utility.

Background: The benefits of preventive interventions lack comprehensive evaluation in standard health technology assessments (HTA), particularly for rare and transmissible diseases. Objective: To identify possible considerations for future HTA using analogies between the treatment and prevention of rare diseases. Study design: An Expert panel meeting assessed whether one HTA assessment framework can be applied to assess both rare disease treatments and preventive interventions. Experts also evaluated the range of value elements currently included in HTAs and their applicability to rare, transmissible, and/or preventable diseases. Results: A broad range of value should be considered when assessing rare, transmissible disease prevention. Although standard HTA can be applied to transmissible diseases, the risk of local outbreaks and the need for large-scale prevention programs suggest a modified assessment framework, capable of incorporating prevention-specific value elements in HTAs. A 'Rule of Prevention' framework was proposed to allow broader value considerations anchored to severity, equity, and prevention benefits in decision-making for preventive interventions for rare transmissible diseases. Conclusion: The proposed prevention framework introduces an explicit initial approach to consistently assess rare transmissible diseases, and to incorporate the broader value of preventive interventions compared with treatment.

Seasonal influenza causes many cases and related deaths in Europe annually, despite ongoing vaccination programs for older adults and people at high-risk of complications. Children have the highest risk of infection and play a key role in disease transmission. Our cost-utility analysis, based on a dynamic transmission model, estimated the impact of increasing the current vaccination coverage with inactivated quadrivalent influenza vaccine in Germany to all (healthy and high-risk) children under 5 years of age (40% uptake), or under 18 years (40% uptake), or only high-risk children under 18 years (90% uptake). Eight influenza complications were modeled, hospitalization and death rates were based on age and risk status. All three vaccination strategies provided more health benefits than the existing vaccination situation, reducing influenza cases, complications, hospitalizations and deaths across the entire population. The strategy targeting all children under 5 years was highly cost-effective (euro6/quality-adjusted life-year gained, payer perspective). The other strategies were cost saving from the payer and societal perspectives. The vaccination strategy targeting all children under 18 years was estimated to provide the most health benefits (preventing on average 1.66 million cases, 179,000 complications, 14,000 hospitalizations and 3,600 deaths due to influenza annually) and the most cost savings (annually euro20.5 million and euro731.3 million from payer and societal perspectives, respectively). Our analysis provides policy decision-makers with evidence supporting strategies to expand childhood influenza vaccination, to directly protect children, and indirectly all other unvaccinated age groups, in order to reduce the humanistic and economic burden on healthcare systems and society. Plain Language Summary What is the context? Every winter, millions of people in Europe become ill due to influenza (flu), and some need to be hospitalized for complications that can sometimes lead to death. While mainly older adults and people with chronic illness are at higher risk of complications from influenza, children have the highest risk of infection and of transmitting the disease. Current vaccination policies in Europe, including Germany, target older adults and high-risk populations (pregnant women, children and other age groups with chronic diseases). What is new? This analysis simulates the effects of expanding current German vaccination programs in high-risk children to include healthy children, and of increasing vaccination coverage rates, for direct protection against infection, and to reduce the disease transmission in the rest of the population. We modeled three vaccination strategies: vaccinating 40% of all (healthy and high- risk) children under 5 years old; vaccinating 40% of all (healthy and high-risk) children under 18 years old; vaccinating 90% of high-risk children under 18 years old. What is the impact? All three strategies resulted in health gains, as more influenza cases, complications and deaths were prevented in all age groups of the population compared to the current situation. The strategies targeting both healthy and high-risk children provided the greatest health benefits. In particular, a vaccination policy targeting all children under 18 years old was predicted to provide the most health benefits as well as the highest cost savings: the increased costs of vaccination were more than offset by the savings in disease management costs as a result of having fewer influenza patients. Vaccinating healthy children against influenza is expected to significantly reduce the disease burden in the total population while saving costs, due to reduced transmission of the disease.

Children have a high burden of influenza and play a central role in spreading influenza. Routinely vaccinating children against influenza may, thus, not only reduce their disease burden, but also that of the general population, including the elderly who frequently suffer severe complications. Using the published individual-based tool 4Flu, we simulated how pediatric vaccination would change infection incidence in Germany. Transmission of four influenza strains was simulated in 100,000 individuals with German demography and contact structure. After initialization with the recorded trivalent influenza vaccination coverage for 20 years (1997–2016), all vaccinations were switched to quadrivalent influenza vaccine (QIV). Scenarios where vaccination coverage of children (0.5-17-year-old) was increased from the current value (4.3%) to a maximum of 10-60% were compared to baseline with unchanged coverage, averaging results of 1,000 pairs of simulations over a 20-year evaluation period (2017–2036). Pediatric vaccination coverage of 10-60% annually prevented 218–1,732 (6.3–50.5%) infections in children, 204–1,961 (2.9–28.2%) in young adults and 95–868 (3.1–28.9%) in the elderly in a population of 100,000 inhabitants; overall, 34.1% of infections in the total population (3.7 million infections per year in Germany) can be prevented if 60% of all children are vaccinated annually. 4.4–4.6 vaccinations were needed to prevent one infection among children; 1.7–1.8 were needed to prevent one in the population. Enhanced pediatric vaccination prevents many infections in children and even more in young adults and the elderly.