Journal of Medical Economics

Aims: COVID-19 and influenza continue to impose a substantial burden on the Canadian healthcare system, particularly among adults aged greater than 65 years. This study compared the clinical and economic outcomes of a Stand-alone vaccination strategy with separate influenza and COVID-19 vaccines versus a Combination strategy incorporating mRNA-1083, an investigational vaccine targeting both infections. Methods: The study adopted the public healthcare payer perspective and adapted a previously published static model to predict COVID-19 and influenza infections across a one-year time horizon. Relative vaccine effectiveness (rVE) for mRNA-1083 against COVID-19 compared with the stand-alone vaccine (SPIKEVAX) was based on the pivotal clinical trial of mRNA-1083s COVID-19 component (mRNA-1283). For influenza, no incremental VE was assumed versus the adjuvanted stand-alone vaccine (FLUAD). Infections were modeled independently. Clinical outcomes included symptomatic infections, hospitalizations, and deaths. The economically justifiable price (EJP) was calculated at the willingness-to-pay (WTP) threshold of $50,000 per quality-adjusted life-year (QALY) gained. mRNA-1083 uptake was assumed to yield absolute increases in COVID-19 and influenza coverage by 10% and 3%, respectively. Results: Compared with the Stand-alone strategy, the Combination strategy was projected to reduce the number of COVID-19-related symptomatic infections, hospitalizations, and deaths (n=71,074; 5,008; 935, respectively), and corresponding influenza outcomes (n=3,985; 362; 69, respectively). The use of mRNA-1083 within the Combination strategy generated a cost-savings of $90,440,471 in vaccine administration fees and an EJP of $304 per dose. Results were sensitive to rVE, coverage, administration fees, mortality and incidence. Limitations: mRNA-1083s rVE is being evaluated in clinical trials and the impact of mRNA-1083 on vaccine coverage and administration fees is uncertain. Conclusions: mRNA-1083 may reduce the burden of COVID-19 and influenza in adults aged greater than 65 years in Canada, while offering good economic value because it has the potential to increase coverage and VE while reducing administration fees.

Breast cancer was the leading cause of cancer-related mortality among women worldwide in 2022. In Kenya, more than a quarter of breast cancer patients have the aggressive Human Epidermal Growth Factor Receptor 2 positive subtype. Trastuzumab is recommended for its treatment, but high costs have limited access. This study evaluated the cost-effectiveness and affordability of trastuzumab-based regimens to inform their adoption and use in Kenya. A cost-utility analysis was conducted from the healthcare payer perspective over a lifetime horizon. Five trastuzumab-based regimens of varying durations (9-week, 6-month, 9-month, 12-month, and 24-month) were compared with chemotherapy alone. Direct medical costs were estimated using a bottom-up micro-ingredient approach. All costs were reported in 2022 USD. A cohort Markov state-transition model with a monthly cycle length was used to estimate the costs and outcomes for an open hypothetical cohort. Scenario, deterministic sensitivity and probabilistic sensitivity analyses were conducted. A budget impact analysis estimated the financial implications of each regimen. The 9-week regimen had the lowest incremental cost-effectiveness ratio (ICER) of USD 3,230 per QALY, while the remaining regimens had ICERs ranging from USD 4,046 to 9,846 per QALY. The findings were most sensitive to the price and quantity utilized per cycle of trastuzumab. A reimbursement cap of KES 40,000 per cycle reduced ICERs by up to 61%. Over five years, the 9-week regimen would account for 1.2% of the projected insurers budget, whereas the current recommended 12-month regimen would consume 2.82%. Although none of the regimens were cost-effective at Kenyas WTP threshold (USD 1054.80), the 9-week regimen may still be considered by policymakers given its greater affordability. Further cost reductions can be achieved through negotiating lower drug prices, improving access to biosimilars, and implementing vial sharing.

BackgroundCell and gene therapies (CGT) represent a transformative class of medical interventions, yet their high production costs limit patient access. Understanding the structure of manufacturing costs is essential for informing policies that can expand access to these therapies. ObjectiveThis study develops and applies a cost-of-goods-sold (COGS) model to analyze the contributors to manufacturing costs for mRNA-based CGT, with application to a wide range of current and future therapies. MethodsAn Excel-based COGS model was constructed based on cost categories for CGT. Two mRNA-based products at commercial scale were used to populate the model: an mRNA vaccine and a therapeutic mRNA gene therapy. Cost inputs were drawn from vendor pricing, peer-reviewed and grey literature, and expert consultation with CGT manufacturing specialists. Three scenarios (worst, base, and best case) were modeled across six cost categories: materials, consumables, capital, labor, licenses, and royalties. A tornado diagram sensitivity analysis was conducted to identify key cost drivers. The mRNA vaccine was used to build and validate the model strucutre using publicly available data sources. The therapeutic mRNA therapy was used as the main use case for illustration and sensitivity analysis. ResultsUnder base-case assumptions, the estimated cost per dose for the therapeutic mRNA product is $56.09, ranging from $3.68 (best case) to $383.22 (worst case). Licensing and royalty fees together account for approximately 83% of total base-case COGS ($6,996,000 and $6,960,000 per production run, respectively, out of $16,825,597 total). Excluding these fees, material costs represent the largest remaining share (61%), followed by consumables (34%), capital (4%), and labor (1%). Sensitivity analysis confirms that licensing and royalty assumptions are the dominant source of uncertainty in the model. ConclusionsLicensing and royalty fees are the primary driver of mRNA-based CGT production costs and represent the greatest opportunity for cost reduction through policy intervention. Strategic priorities for cost reduction should focus on optimizing reagent utilization, increasing platform potency, and expanding use of contract development and manufacturing organizations (CDMOs) to reduce capital and labor costs. Key PointsProducing an example mRNA gene therapy costs about $56 per dose to manufacture, driven almost entirely driven by fees paid to patent holders for the underlying technology. Licensing and royalty fees cost roughly 83 cents of every dollar spent on these new biopharmaceutical products. Until that changes, the gap between what therapies cost to make and what patients and payers are charged will remain very wide.

Background Despite the significant impact of longstanding paediatric pneumococcal conjugate vaccine (PCV) use in the United Kingdom (UK), pneumococcal disease burden remains substantial and is primarily driven by nonPCV13 serotypes. Higher valent vaccines such as the 20 valent PCV (PCV20) may provide additional public health and economic benefits, yet their value in the contemporary UK setting has not been fully assessed using recent data. Methods We updated an age structured dynamic transmission model using post COVID 19 UK epidemiology (2001 to 2023) to compare pediatric PCV20 with PCV13 and PCV15. Over a 10 year horizon, we assessed cost effectiveness and number needed to vaccinate (NNV), capturing invasive and non invasive disease cases, deaths, costs, quality adjusted life years, and incremental cost effectiveness ratios. PCV20 was evaluated under 1+1 and 2+1 schedules; PCV13 and PCV15 were assessed under 1+1. Scenario analyses examined key uncertainties. Results PCV20 was estimated to avert more cases and deaths than PCV13 or PCV15, driven by broader serotype coverage and indirect effects. Both PCV20 schedules were dominant or cost saving versus lower valent comparators, with lower NNVs. PCV20s higher vaccination costs were offset by reductions in downstream healthcare expenditures. Conclusion Paediatric PCV20 implementation in the UK could deliver substantial health gains while improving economic efficiency, supporting timely adoption.

Background Catch-up vaccination will be pivotal for achieving WHOs cervical cancer elimination goals in low- and middle-income countries (LMICs). We assessed the health-economic impact of catch-up HPV vaccination for females in LMICs. Methods Using IARCs METHIS modelling platform and data from 132 LMICs, we simulated HPV catch-up vaccination beyond the primary target age, varying the maximum age up to 30 years. Budget impact was expressed as a share of national five-year immunization budgets and current health expenditure. We conducted cost-effectiveness analyses for a smaller subset of countries for which high-quality cervical cancer treatment costs were available. Findings Catch-up HPV vaccination up to age 30 in LMICs could prevent 9.2 million cervical cancer cases over the lifetime among females aged 9-30 years. Across countries, budget impact ranged from 0.007%-2.24% of five-year health expenditure and 0.002%-236.65% of immunization budgets, with vaccine procurement comprising about 70% of costs. Gavi support could reduce costs by nearly 70% for catch-up up to age 18. Catch-up vaccination up to age 30 was cost-effective in almost all evaluated countries, except in one where cost-effectiveness was achieved up to age 21. Interpretation In LMICs, after achieving adequate coverage in the primary target group (9-14 years), expanding HPV catch-up vaccination would be impactful and cost-effective. Sustainable financing, Gavi support, and cost-minimization strategies are crucial for successful catch-up programmes and progress toward cervical cancer elimination.

Suboptimal rotavirus vaccine effectiveness in low- and middle-income countries (LMICs) highlights the need for next-generation vaccines, such as the neonatal RV3-BB vaccine. However, there is uncertainty in the duration of protection and future price of vaccines in development. We aim to identify the conditions under which switching to RV3-BB is optimal in Malawi and Ghana, where the current immunization programs use 2-dose Rotarix and 3-dose Rotavac schedules, respectively. A full incremental cost-effectiveness analysis was performed using a validated transmission model calibrated to country-specific rotavirus data. Over 2025-2034, introducing RV3-BB resulted in the largest rotavirus-related burden reduction compared with the current country-specific programs. At moderate willingness-to-pay (~0.5 time Gross Domestic Product per capita), RV3-BB was preferred over Rotavac if price per dose was <$1.2 in Malawi and <$2.5 in Ghana, and/or if the average duration of protection exceeded 40 weeks in Malawi. The RV3-BB vaccine is likely to be cost-effective in Malawi and Ghana, as well as other LMICs, based on expected pricing and duration of protection.

ImportanceCesarean delivery is the most common surgery in the US with more than 1 million performed each year; it is also the most significant risk factor for postpartum infection. The Cesarean Section Optimal Antibiotic Prophylaxis trial demonstrated that the addition of azithromycin at the time of cesarean birth performed in labor reduces postpartum infection. ObjectiveTo determine the real-world adoption and effect of this trial on clinical practice and postpartum infections among U.S. pregnant persons undergoing cesarean delivery in labor. DesignDifference-in-differences analysis from 2013-2024. SettingPopulation-based, patient-level analysis using Epic Cosmos, a large longitudinal national electronic health record database of patients seen in health systems using Epic. ParticipantsPregnant individuals who received outpatient prenatal care in the system, who labored and gave birth to a liveborn singleton infant at 24-43 weeks of gestation were included. Exclusion criteria included unknown mode of delivery and intraamniotic infection. ExposuresThe treatment group included those delivered by cesarean and the control group included those who delivered vaginally. The pre-period was defined as 2013-2016, excluding a washout period from trial publication until December 31, 2016, and the post-period was defined from 2017-2024. Main Outcomes and MeasuresThe primary outcomes were perioperative azithromycin administration and postpartum infection within 6 weeks of delivery. Results1,663,341 participants were included in the final analysis. In the pre- and post-periods, azithromycin was administered in 0.01% and 0.04% of vaginal births and in 2.2% and 39.6% of cesarean births, respectively. In the pre- and post-periods, postpartum infection occurred in 2.0% and 2.7% of vaginal births and 9.2% and 8.0% of cesarean births. In the adjusted difference-in-difference analysis, the trial resulted in an absolute increase in azithromycin use by 37.6 percentage points (pp) (95% CI: 33.1 to 42.2 pp); postpartum infection decreased by 2.0 pp (95% CI: -2.5 to -1.4 pp), a relative decrease of 20%. Conclusions and RelevanceOutside the clinical trial setting, this study provides evidence that azithromycin significantly reduces postpartum infection among pregnant persons undergoing a cesarean delivery in labor. Key PointsO_ST_ABSQuestionC_ST_ABSDid evidence from the Cesarean Section Optimal Antibiotic Prophylaxis (C/SOAP) trial change real-world clinical practice and decrease postpartum infections among U.S. pregnant persons who underwent a cesarean delivery in labor? FindingsIn this difference-in-differences analysis of 1.6 million births, azithromycin use increased 37.6 percentage points and postpartum infections decreased by 2.0 percentage points following the C/SOAP trial. MeaningOutside the clinical trial setting, this study provides evidence that azithromycin significantly reduces postpartum infection among individuals having a cesarean delivery in labor.

Pre-eclampsia (PE) is a major contributor to maternal and neonatal morbidity and mortality. Research in high-income countries has shown that biomarker-based PE screening can improve timely detection and management of women at high risk of PE. We conducted a pre-trail cost-effectiveness analysis of introducing biomarker screening in Tanzania to identify key parameters informing a full, trial-based economic evaluation. We developed a decision tree comparing current practice with two biomarker-based screening strategies: Strategy 1 introducing placental growth factor (PlGF), and Strategy 2 adding soluble fms-like tyrosine kinase-1 (sFlt-1)/PlGF ratio. Under both strategies we assumed early aspirin prophylaxis and/or close monitoring for high-risk women. For each of the three options, we modelled PE diagnosis, as well as maternal and neonatal outcomes over a one-year time horizon, assuming a healthcare sector perspective. We quantified health outcomes in terms of disability-adjusted life years (DALYs) and costs in 2023 US$. When compared to current practice, the incremental cost per DALY averted was $410.45 for Strategy 1 and $1,011.78 for Strategy 2. Limiting the novel strategies to nulliparous women, decreased incremental cost-effectiveness ratios to $184.15 (Strategy 1) and $413.33 (Strategy 2). Key parameters impacting cost-effectiveness were PE prevalence, biomarker screening accuracy, adherence to and effectiveness of preventive treatment and monitoring, and related costs. Based on our findings, biomarker screening has the potential to be cost-effective in Tanzania, particularly if introduced early in pregnancy and targeted at nulliparous women. Further research in low-resource settings is needed to overcome the current data and evidence gaps.

PurposeNeurogenic dysphagia is prevalent in neurological inpatients and associated with adverse outcomes, yet its independent economic impact after adjustment for frailty and functional status remains poorly quantified. We aimed to estimate the independent effect of dysphagia on hospital length of stay (LOS) and costs, to test whether this effect differs between geriatric and non-geriatric patients, and to quantify the probability and magnitude of cost savings from improvements in swallowing function. MethodsWe analysed 10,375 neurological inpatient cases (2021-2024) at a German university hospital. Dysphagia was defined by fiberoptic endoscopic evaluation of swallowing (FEES) or ICD-10 R13 coding (n = 1,382; 13.3%). Bayesian Gamma-log regression with informative priors from historical data and published literature was used to model LOS and total case costs (German DRG), adjusted for age, sex, Hospital Frailty Risk Score (HFRS, R13-adjusted), self-care index ("Selbstpflege-Index", SPI), stroke status, and emergency admission. A geriatric cohort was defined as age [&ge;]70 and adjusted HFRS [&ge;]5 (n = 2,053; 19.8%). Posterior predictive simulation estimated cost savings for hypothetical improvements of 1-3 points on the Functional Oral Intake Scale (FOIS). ResultsAfter comprehensive adjustment, dysphagia was independently associated with 46.5% longer LOS (posterior ratio 1.465; 95% credible interval [CrI] 1.397-1.537) and 28.2% higher total case costs (ratio 1.282; CrI 1.213-1.354). The dysphagia x geriatric interaction was small but credible and ran in opposite directions: slightly attenuated for LOS (interaction ratio 0.908, CrI 0.837-0.986) but slightly amplified for costs (1.096, CrI 1.012-1.185), consistent with complexity-driven DRG grouping in geriatric patients. The absolute economic burden remained larger in the geriatric cohort due to higher baseline costs. In the geriatric cohort, a one-point FOIS improvement yielded a 74.3% posterior probability of LOS-based savings (mean {euro}555/case); at three points, this rose to 84.2% (mean {euro}1,115/case). The direct cost model confirmed high benefit probabilities from the payers perspective (82.6% at {delta}FOIS = 3). ConclusionsNeurogenic dysphagia is an independent and substantial driver of hospital LOS and costs in neurological inpatients, even after adjustment for frailty and functional status. The proportional effect on costs is slightly larger in geriatric patients, while the LOS effect is slightly smaller, consistent with the mechanics of the G-DRG system. Bayesian simulation indicates that improvements in swallowing function carry a high probability of generating cost savings, supporting the characterisation of dysphagia as a modifiable economic target with particular relevance to geriatric neurology.

Objectives: To evaluate if direct access to a Pregnancy Early Access Center (PEACE) improves the timeliness and efficiency of pregnancy loss care. Methods: We conducted a retrospective cohort study of patients diagnosed with EPL from January 2017 to December 2022 within a single healthcare system. We included EPL patients treated with procedural or medication management who had been assessed for a related early pregnancy complaint in the thirty days prior. The exposure was direct utilization of PEACE (yes/no) between first EPL symptom visit and EPL management. The primary outcome was "care latency" defined as days from initial presentation for concerning early pregnancy symptoms to initiation of active management. Secondary outcomes included "care continuity," the number of care teams encountered, "care efficiency," the number of patient encounters, and the type of EPL management received. Results: The evaluable cohort included 2151 individuals, with 36.5% patients of Black race and 30.3% publicly insured. A total of 885 (41.1%) received any EPL care at PEACE and 246 (11.4%) initiated their care at PEACE. Patients initiating care through PEACE experienced a 5-day reduction in care latency compared to patients who did not access PEACE. Adjusting for age, race, and insurance type, patients whose index EPL visit was with PEACE initiated their treatment twice as quickly as those who never saw PEACE (aHR 2.36 [95% CI, 2.05-2.71]). Care efficiency (median 2 [1-3] encounters) and care continuity (median 4.5 [4-7] care teams) were also improved by an index visit with PEACE when compared with controls (3 [2-4] and 6 [4-8] p<0.01), respectively). Conclusions: The Pregnancy Early Access Center (PEACE) model is associated with reduced care latency and improved efficiency and continuity when compared with routine care. PEACE reduces barriers to timely, patient-centered early pregnancy care.

INTRODUCTIONIn 2021, the Society for Maternal-Fetal Medicine updated its guidance on late preterm antenatal steroids, which included a recommendation to engage in shared decision-making on the risks and benefits. The objective of this study was to assess the effects of this updated guidance on the practice among a contemporary cohort of US births. METHODSThis retrospective cohort study implemented an interrupted time series (ITS) design among late preterm singleton births using encounter-level inpatient data from the Premier Healthcare Database (PHD). A 3-year observational period before (January 1, 2019, to December 31, 2021) and after (January 1, 2022, to December 31, 2024) the intervention date (selected as January 1, 2022) was defined to quantify whether the guideline was associated with changes in obstetric practice. Steroid exposure was modeled at the patient level as a binary outcome using Poisson regression with a log-link function, with a linear spline at the intervention knot to estimate both the pre-intervention slope and the change in slope following guideline dissemination. The change in slope at the knot was the primary parameter of interest. Time was measured in quarters. Incidence rate ratios can be interpreted as quarter percent changes (QPCs) in the rate of ACS use and are presented with 95% confidence intervals (CIs). RESULTS: 342,925 late preterm deliveries were included in the analysis: 176,938 in the pre-period and 165,987 in the post-period. 57,372 (32.4%) in the pre-period were exposed to late preterm steroids, and exposure rates were stable over time (adjusted QPC (aQPC) 1.01; 95% CI: 1.00, 1.01). Following guideline dissemination, steroid exposure rates declined by 3% per quarter (aQPC 0.97; 95% CI: 0.96, 0.98), indicating a significant change in the trajectory of steroid use among the population targeted by the guideline. In quarter 4 of 2024 (the end of the study period), the exposure rate decreased to 25.1%. CONCLUSIONLate preterm steroid exposure decreased significantly after SMFM updated its clinical guidance, which newly highlighted the conflicting long-term data and recommended shared decision-making about the risks and benefits. Future research on the long-term risks and benefits of ACS is needed to inform clinical practice guidelines and shared decision-making. Key PointsFollowing SMFMs 2021 updated guidance on late preterm antenatal corticosteroids, which highlighted uncertain long-term neurodevelopmental risks and recommended individualized counseling, steroid exposure among late preterm births declined by approximately 3% per quarter in a nationally representative US cohort.

BackgroundSubcutaneous oncology monoclonal antibodies (SCOmAbs) offer significant benefits compared to intravenous formulations, including reduced administration time and potential for self-administration. However, little has been published on real-world preparation and administration practices with these novel formulations. MethodsThis was a qualitative, exploratory study of 30 participants (10 patients receiving SCOmAbs, 10 nurses, and 10 pharmacists/pharmacy technicians) across various U.S. healthcare facilities. One-on-one, in-depth interviews examined current practices, pain points, device integration potential, projected impact of increased SCOmAb adoption, and perspectives on home administration. ResultsFindings revealed considerable variability in SCOmAb preparation and administration practices. While preparation methods generally aligned with typical parenteral workflows, notable deviations included bedside preparation by nurses (7/30), use of syringe pump modules (3/19), and one case of patient self-administration at home. Most participants utilized closed-system transfer devices (12/22) despite inconsistent hazardous drug treatment between facilities. Administration challenges included ergonomic difficulties for nurses during manual push (5/9 reporting physical discomfort) and variable injection techniques to accommodate patient comfort. Nurses reported significant workflow impact from being "tethered" to patients during administration, which could require staffing adjustments as SCOmAb frequency increases. Most patients (6/9) expressed interest in home administration for potential time savings and flexibility, though concerns about training, support, and safety were common. ConclusionsAs SCOmAb utilization expands, facilities may face barriers associated with increased demand that could necessitate innovative solutions. To leverage the full potential of SCOmAb products, developers should consider how next generation product presentations might minimize identified pain points, streamline administration, and facilitate safe transition to home self-administration. Delivery device integration, whether through prefilled syringes, portable infusion pumps, or other delivery systems, may address current challenges but requires careful consideration of facility infrastructure, product complexity and usability, workflow impact, and patient training requirements.

Objective: To externally validate a risk stratified delivery timing model for nulliparous, term, singleton, vertex (NTSV) cesarean reduction using national data. Design: Population based cohort study of NTSV births in US National Vital Statistics System (NVSS) natality files, 2020 to2024, using logistic regression for cesarean predictors and risk stratified Monte Carlo simulation (10,000 iterations per strategy and risk group) to evaluate delivery timing policies. Setting: All live births in the US recorded in the NVSS natality files. Participants: NTSV patients with term (37+ weeks) pregnancies and complete gestational age and delivery mode data (N=5 776 412). A sensitivity cohort excluded pre 39 week deliveries and pregnancies with preexisting diabetes or hypertension. Exposures: Delivery timing strategies defined by gestational age and labor onset (elective induction at 39, 40, or 41 weeks, or expectant management to 42 weeks), evaluated within maternal age and body mass index (BMI) risk strata (low: age <35 and BMI <30; moderate: age > 35 or BMI > 30; high: age > 35 and BMI > 35). Main Outcomes and Measures: Primary outcome was cesarean delivery, measured as the proportion of deliveries completed by cesarean across gestational ages, labor onset types, and age BMI strata. Secondary outcomes included gestational age specific cesarean rates, area under the receiver operating characteristic curve (AUC) for cesarean prediction, and simulated mean cesarean rates with 95% simulation intervals under four delivery timing strategies within each risk group. Results: The overall NTSV cesarean rate was 26.4%. Cesarean Rates were U shaped across gestational ages, with the lowest rate at 38 weeks (24.9%) and higher rates at 37 weeks (29.8%) and 41 to 42 weeks (28.1 to 28.5%). Risk group distribution was 64.9% low, 33.7% moderate, and 1.4% high. Model AUC was 0.65. Induction had higher cesarean rates than spontaneous labor (29.3% vs 24.2%; odds ratio 1.30, 95% confidence interval 1.29 to 1.30). Monte Carlo simulation favored induction at 39 weeks for high risk patients (59.3%) and expectant management to 41 to 42 weeks for low risk patients (19.1%). Conclusions and Relevance: A risk stratified NTSV labor management model showed external validity in 5.8 million US births and consistently identified risk-specific timing strategies that lowered cesarean rates, supporting individualized delivery timing policies.

IntroductionThe link between Human Papillomavirus (HPV) and cancer is well-established. In Singapore, bivalent HPV vaccines are subsidised for females, but not males. Economic analysis of HPV vaccination has generally assessed the costs to the health system, but this may not be as relevant to individual decision-making as potential lost income. We estimated the impact of bivalent HPV 16/18 vaccination on sick leave, unemployment, and premature mortality as a function of age and sex to understand the broader impact of HPV-related cancers. MethodsWe developed a population-level economic model to estimate lifetime income losses by diagnosis age, sex and cancer type. We applied sex- and cancer-specific Cox regressions to the Singapore Cancer Registry for annual predicted survival from 1992 to 2022. These were combined with census and employment data to estimate HPV-associated income losses in Singapore. Attributable fractions and vaccine effectiveness data for HPV 16/18 from the literature were used to estimate the effectiveness of bivalent HPV vaccination. Structural sensitivity analysis examined the role of 80% population coverage conferring herd immunity. ResultsThe registry contained 17,294 individuals with an HPV-associated cancer diagnosis. Lost income was greatest for cervical cancer due to its high prevalence, however the losses per diagnosis were highest for oropharyngeal cancer. Bivalent HPV vaccination led to income benefits of $SGD1,397 [$895 to $1,838] in girls and -$62 [- $76 to -$48] in boys. A gender-neutral HPV vaccination of 80% of 15-year-old Singaporeans, conferring herd immunity, would have lifetime income protective benefits of $24.4m [$14.2m, $33.7m] per cohort, a five-fold return on investment. ConclusionsIn addition to avoiding healthcare costs and lost quality of life, parents should consider vaccination as a means of avoiding potential income losses. A national policy of gender-neutral HPV vaccination could deliver substantial income protection due to both individual vaccine protection and herd immunity.

Objectives: Influenza is a widespread acute respiratory illness posing a major public health challenge for both the National Health Service (NHS) and society, particularly among older adults. This study aimed to assess the cost-effectiveness of high-dose quadrivalent vaccine (HD-QIV) versus adjuvanted quadrivalent vaccine (aQIV) in older adults in Spain. Methods: Public health and economic benefits were evaluated using a decision-tree model considering influenza cases, GP and ED visits, hospitalizations, and influenza-related mortality. Deterministic and probabilistic sensitivity analyses addressed epidemiological and economic uncertainties. Results: From a societal perspective, HD-QIV prevented 54,039 influenza cases, 7,733 GP consultations, 1,585 ED visits, 27,398 episodes of hospitalization due to cardiorespiratory events over a single influenza season and 1,203 deaths compared to aQIV when vaccinating adults [&ge;]65 years old in Spain, resulting in 14,316 LYs and 12,440 QALYs gained over a lifetime horizon. The reduction in health outcomes outweighed the increase in vaccination costs, translating to a reduction in total costs with HD-QIV compared to aQIV. Therefore, vaccinating older adults in Spain with HD-QIV instead of aQIV was a dominant strategy when evaluating hospitalizations due to respiratory and cardiovascular events. HD-QIV remained dominant from a NHS perspective. Sensitivity analyses confirmed the robustness of the model. Conclusions: This analysis showed that vaccinating older adults in Spain with HD-QIV instead of aQIV would reduce influenza cases, GP and ED visits, hospitalizations, deaths, and associated costs, and thus it should be the strategy of choice in a situation of budgetary constraints from either a societal or an NHS perspective.

Background: The impact of the Inflation Reduction Act (IRA) upon late-stage developments has been assumed to be limited. The Congressional Budget Office's IRA analysis excluded post-approval innovation, potentially overlooking substantial economic risks to drug developers and declines in the availability of treatments in areas of high unmet medical need such as oncology. Methods: A total of 1148 secondary trials from 364 FDA-approved medicines, published from 2018 to 2025, were obtained from Biomedtracker and clinicaltrials.gov. Using fractional multinomial logit, we model the share distribution of secondary indication studies across 19 disease groups and assess the change in this distribution post-IRA. We also assessed the number of secondary treatment studies pre- vs. post-IRA using multiple linear regression. Results: After the IRA's introduction, small molecule follow-on studies in oncology exhibited a statistically significant 35% decline (R2 = .48, p < 0.014) and lead indication small molecule oncology approvals exhibited a statistically significant 27% decline (R2 = .70, p < 0.002). We also find a statistically significant 14% decline in the share of orphan oncology studies pre- vs. post-IRA (p<0.001). Research Conclusions: This study's results refute claims that the IRA would have minimal negative effects on patient access or late-stage biopharmaceutical R&D. We hope this study reinvigorates debate about the law's unintended consequences and encourages thoughtful policy solutions, as the IRA manifestly creates disincentives that negatively impact patients seeking needed new medicines, particularly those requiring cures addressing metastatic late-stage cancers.

Objective: To develop and validate a multivariable prediction model and clinically actionable risk score for vaginal birth after cesarean (VBAC) success using machine learning, and to integrate neonatal morbidity outcomes into a decision-analytic framework for trial of labor after cesarean (TOLAC) counseling. Methods: We performed a retrospective cohort study of 1,418 consecutive TOLAC cases at a single tertiary care center in California from 2019 through 2025. Multivariable logistic regression and four machine learning algorithms (logistic regression, random forest, gradient boosting, extreme gradient boosting) were trained using 5-fold stratified cross-validation. A cumulative risk score (negative 1 to 7 points) was constructed from independently significant predictors. Neonatal intensive care unit (NICU) admission rates and uterine rupture rates were evaluated across risk strata. Results: The overall VBAC rate was 76.7% (1,087/1,418). Penalized logistic regression achieved the highest cross-validated AUC (0.71, 95% CI 0.67 to 0.75). A parsimonious multivariable logistic model used for score derivation had an AUC of 0.70 (95% CI 0.67 to 0.73). Independent predictors of failed TOLAC included induction of labor (adjusted odds ratio [aOR] 1.93, 95% CI 1.48 to 2.52), hypertensive disorders (aOR 1.60, 95% CI 1.19 to 2.15), diabetes mellitus (aOR 1.71, 95% CI 1.19 to 2.47), obesity (body mass index [BMI] 30 or greater; aOR 1.46, 95% CI 1.11 to 1.90), maternal age of 40 years or older (aOR 1.49, 95% CI 0.89 to 2.50), and gestational age of 41 weeks or greater (aOR 2.22, 95% CI 1.40 to 3.52). Prior vaginal delivery was independently protective (aOR 0.37, 95% CI 0.28 to 0.48). The cumulative risk score stratified VBAC success from 89.1% (score negative 1) to 37.8% (score 4 or higher). NICU admission rates increased concordantly from 31.7 to 200.0 per 1,000 across risk strata negative 1 through 4 or higher (Spearman rho 0.94, P for trend = .005). Uterine rupture occurred in 28 cases (1.97%) and was associated with severe maternal morbidity (10.7% vs 0.7%; odds ratio 16.56, P < .001) but was not predicted by any antepartum risk factor. Exclusion of patients with risk scores of 3 or higher (11.3% of the cohort) improved overall VBAC success to 80.0% (P = .04) and reduced NICU rates to 66.0 per 1,000. Conclusion: A machine learning to derived cumulative risk score incorporating prior vaginal delivery as a protective factor identifies TOLAC candidates with poor VBAC prognosis and elevated neonatal morbidity, providing an evidence-based tool for individualized delivery counseling. Uterine rupture remains unpredictable by antepartum characteristics.

Introduction Care home (CH) influenza vaccination of staff improves resident health, yet uptake remains low at just over 11% (England, 2025/2026). We report an economic evaluation (EE) of "FluCare", an intervention to increase staff influenza vaccination through: vaccination clinics at CHs; promotional materials; and CH financial incentives. Method Seventy-five CHs were randomised to FluCare or control. A cost-consequence analysis took the influenza vaccination programme funder perspective, but also extended to the National Health Service (NHS) and CH perspective. Costs included: influenza vaccination; administration fee; FluCare components; CH resident NHS utilisation. Outcomes were: staff influenza vaccination rates; staff sickness; and resident mortality. Sensitivity analyses excluded intervention CHs that did not host vaccination clinics. Results Compared to control CHs, adjusted analysis found intervention homes with a mean absolute increase in vaccination rates of 1.8% (95% CI: -6.0%, 10.8%; p=0.572) at an increased cost of {pound}451 (95% CI: {pound}239, {pound}675; p<0.001) to the vaccination programme funders: {pound}249 per additional percentage point (PAPP) per CH. Vaccination clinics were delivered late in the influenza season, with 80% taking place from February 2023. Including only intervention CHs that hosted staff flu vaccination clinics (23/35), increases the mean difference to 10.1% (95% CI: 0.9%, 21.9%; p=0.018) and costs to {pound}805 (95% CI: {pound}603, {pound}1,079; p<0.001): {pound}79 PAPP per CH. Differences between trial arms in other costs and outcomes were marginal and generally non-significant. Conclusions FluCare delivered little improvement when staff flu vaccination clinics did not occur and had little impact on other costs/outcomes. Cost-effectiveness depends on willingness-to-pay for increased staff vaccination, but cost PAPP per CH improved from {pound}249 to {pound}79 when only CHs hosting clinics were considered. Late implementation, likely reduced impact by limiting clinic delivery, as reflected in sensitivity analysis. Future evaluations should implement FluCare earlier in the season.

Introduction: Preeclampsia (PE) is a leading cause of maternal and neonatal morbidity and mortality, and low-dose aspirin (LDA) prophylaxis is the cornerstone of evidence-based prevention. Despite guideline recommendations, LDA adherence remains poor, with 10-25% of moderate-risk patients taking aspirin. Objective personalized risk stratification using biomarkers has been shown to motivate behavior change in other disease contexts. Survey data suggest that patients are more motivated to take aspirin if informed by an objective predictive test. Here, we report real-world LDA adherence among patients who received a high-risk result from a cell-free RNA (cfRNA) PE risk prediction test. Methods: This retrospective, observational survey study included asymptomatic patients of advanced maternal age (AMA; [&ge;] 35 years at delivery) with singleton pregnancies without USPSTF-defined preexisting high-risk conditions for PE who received the cfRNA PE risk prediction test. Patients who opted in to receive text message surveys were asked about LDA use following receipt of test results. High adherence was defined as reporting LDA use on at least 6 of 7 days per week at least 85% of the time surveyed. The primary analysis included patients with a high-risk test result and at least one LDA frequency survey response following receipt of test result. The observed proportion of adherent patients was compared to a baseline estimate of 25% using an exact binomial test. Results: Of 166 patients who received a cfRNA PE risk prediction test result, 48 (28.9%) received a high-risk result. Of these, 29 (60%) opted in and responded to at least one survey, constituting the primary analysis population. Twenty-seven of the 29 (93.1%; 95% CI: 78.0-98.1%) were classified as highly adherent, significantly higher than the 25% baseline adherence estimate for moderate-risk patients (p < 0.0001). Conclusion: Among surveyed patients who received a high-risk cfRNA PE test result, the proportion classified as highly adherent to LDA (93%) substantially exceeded published estimates of adherence in a similar patient population and met the clinically meaningful threshold of [&ge;] 80% associated with reduced risk of preterm preeclampsia. These findings indicate that objective and personalized biomarker risk testing may be a powerful driver of behavior change that current guidelines have failed to produce.

Introduction Data on bloodstream infections (BSI) indicate a growth in incidence over time. This analysis utilised national data from England and the best available United States (US) evidence to predict BSI incidence over the years 2025 to 2029. The analysis utilised evidence on the cost-effectiveness of molecular rapid diagnostic tests (mRDT) to estimate the cost and mortality associated with BSI, and the potential for increased use of mRDT to save lives. Methods Data on BSI incidence by age group and sex for England in 2017 and the US (Minnesota) for 2003 to 2005 were combined with demographic projections over the years 2025 to 2029 to estimate the number of BSIs. Published costs and mortality associated with BSI, according to the method of identification of the pathogen, were used to estimate the lives saved and the cost impact of widespread use of mRDT in England and the US. Results BSI cases in England and the US are predicted to total 1.02 million and 6.24 million over the years 2025 to 2029, associated costs are GBP14.6 million and $221 million, respectively. Expanding the use of mRDT would save 2,219 and 7,554 lives in England and the US, respectively, over a 5-year period and would reduce healthcare expenditure in both countries. Conclusion There is a compelling argument to increase the uptake of mRDT to improve patient outcomes. This analysis demonstrates that expanded mRDT adoption can significantly reduce BSI burden, saving over 9,700 lives and decreasing healthcare expenditure in both countries.