Simon van der Pol

Introduction: Medicine prices change over the product life cycle, especially around loss of exclusivity (LoE), yet economic evaluations often assume constant prices, which may bias cost-effectiveness and budget impact estimates. Methods: We developed and internally validated a forecasting approach for Dutch medicine price trajectories for use in cost-effectiveness analyses. Using monthly Farminform sales data (from 2000 onwards) for 384 Anatomical Therapeutic Chemical (ATC) codes meeting the inclusion criteria (>5 years of data, <6 months missing, data after 2017), we derived inflation-adjusted mean prices per defined daily dose. A stacked machine learning ensemble, combining XGBoost, Random Forest, Bayesian additive regression trees, a regularised generalised linear model, and LightGBM gradient boosting, was tuned by ATC-grouped cross-validation to minimise root mean squared error (RMSE), with weights estimated by non-negative penalised regression. Results: Predictors included therapeutic class and subgroup, market entry period, initial price, revenue group, time on market, LoE status and time since LoE, inflation, and competitor availability. On 103 held-out time series, the six-model ensemble achieved an RMSE of 0.199. Predicted trajectories were highly accurate for 26% of products (within ±5% of observed prices) and of medium accuracy for 47% (overall trend captured; most observations within ±12.5%). Poor accuracy (27%) mainly reflected abrupt price shifts linked to policy changes, reimbursement decisions, or pricing negotiations. Conclusions: Forecasting life-cycle medicine price trajectories is feasible for most products and can support more realistic economic evaluations and reimbursement deliberations in the Netherlands. Remaining challenges include anticipating policy-driven discontinuities and improving interpretability of machine-learning-based forecasts.

Background: COVID-19 remains a substantial public health challenge in the Netherlands. Next-generation COVID-19 vaccine, mRNA-1283, is approved in the European Union, with potential for higher relative vaccine efficacy compared with originally licensed COVID-19 vaccines. Methods: The potential public health and economic impact of mRNA-1283 in adults ≥ 60 years and high-risk adults aged 18–59 years was modeled versus no vaccination and originally licensed mRNA-1273 and BNT162b2, adapting a published static Markov model with a 1-year time horizon. COVID-19 burden reflected two full post-pandemic seasons. Vaccine efficacy versus mRNA-1273 was based on pivotal phase 3 NextCOVE trial data; efficacy versus BNT162b2 was derived from an indirect treatment comparison. The economically justifiable price (EJP) of mRNA-1283 versus no vaccination and price premiums over existing vaccines were determined at a willingness-to-pay threshold of €50,000/quality-adjusted life-year (QALY) gained. Results: Without COVID-19 vaccination, an estimated 460,000 infections, 23,800 hospitalizations, and 5300 deaths would occur. With current coverage, mRNA-1283 was estimated to prevent 68,000 infections, 5400 hospitalizations, and 1200 deaths, saving 9667 QALYs and over €66.5 million in treatment costs. The EJP was €238 versus no vaccination. Compared with mRNA-1273 and BNT162b2, mRNA-1283 was estimated to prevent additional burden (e.g., 1309 and 1679 hospitalizations, respectively) and was cost-effective at an incremental EJP of €62 versus mRNA-1273 and €80 versus BNT162b2. Conclusions: The results support continued COVID-19 vaccination to mitigate the ongoing health and societal burden of SARS-CoV-2 in the Netherlands. The comparative analyses indicate that mRNA-1283 may be associated with substantial health benefits over originally licensed mRNA vaccines; consequently, its use may further improve health outcomes and economic efficiency within COVID-19 vaccination programs.

COVID-19 remains a substantial public health challenge in the Netherlands. Next-generation COVID-19 vaccine, mRNA-1283, is approved in the European Union, with potential for higher relative vaccine efficacy compared with originally-licensed COVID-19 vaccines. Its potential public health and economic impact, in adults ≥60 years and high-risk 18–59 years, was modelled versus no vaccination and originally-licensed mRNA-1273 and BNT162b2, adapting a published static Markov model with 1-year time horizon. COVID-19 burden reflected two full post-pandemic seasons. Vaccine efficacy versus mRNA-1273 was based on pivotal phase 3 NextCOVE trial data; efficacy versus BNT162b2 was derived from an indirect treatment comparison. The economically justifiable price (EJP) of mRNA-1283 versus no vaccination, and price premiums over existing vaccines, were determined at a willingness-to-pay threshold of €50,000/quality-adjusted life-year (QALY) gained. Without COVID-19 vaccination, an estimated 460,000 infections, 23,800 hospitalizations and 5,300 deaths would occur. With current coverage, mRNA-1283 was estimated to prevent 68,000 infections, 5,400 hospitalizations, and 1,200 deaths, saving 9,667 QALYs and over €66.5 million in treatment costs. The EJP was €238 versus no vaccination. Compared with mRNA-1273 and BNT162b2, mRNA-1283 was estimated to prevent additional burden (e.g., 1,309 and 1,679 hospitalizations, respectively), and was cost-effective at an incremental EJP of €62 versus mRNA-1273, and €80 versus BNT162b2. The results support continued COVID-19 vaccination to mitigate the ongoing health and societal burden of SARS-CoV-2 in the Netherlands. The comparative analyses indicate that mRNA-1283 may be associated with substantial health benefits over originally-licensed mRNA vaccines; consequently, it’s use may further improve health outcomes and economic efficiency within COVID-19 vaccination programs.

Background: High-dose inactivated influenza vaccination (HD-IIV) demonstrates superior effectiveness versus standard-dose vaccination (SD-IIV) in adults aged ≥60 years. A recent meta-analysis integrated complementary evidence sources of representing over 85 million individuals across 14 influenza seasons. Methods: A previously developed model was updated using life-time horizon and societal perspective. Updated parameters included demographics, costs, hospitalization rates, and relative vaccine effectiveness (rVE): RCT evidence (24% for ILI, 7% for cardiorespiratory hospitalizations) and RCT + real-world evidence (RWE) (15% for ILI, 8% for cardiorespiratory hospitalizations). Results: HD-IIV resulted in incremental cost-effectiveness ratios of €7,300/QALY (RCT evidence) and €5,800/QALY (RCT+RWE evidence). Implementation would prevent 7,200 general practitioner visits, 6,300 cardiorespiratory hospitalizations, and 269 deaths, by using RCT evidence. Probabilistic sensitivity analysis demonstrated >99% probability of cost-effectiveness at €20,000/QALY threshold for both RCT and RCT+RWE evidence. Conclusions: HD-IIV remains highly cost-effective for Dutch adults aged ≥60 years under updated evidence scenarios, supporting implementation in the national immunization programme. Highlights: The economic analysis of high-dose inactivated influenza vaccine was updated. Relative vaccine effectiveness of HD-IIV incorporating recent evidence was used. HD-IIV remains cost-effective in Dutch adults aged ≥60.

Background: Chronic kidney disease (CKD) is a progressive disease with high societal costs. CKD progression is influenced by patients’ health literacy, i.e., the patients’ ability to deal with information related to their own health. Objective: To assess the cost-effectiveness of Grip on Your Kidneys (GoYK), a multi-component health literacy intervention for CKD patients and their healthcare professionals. Design and Main Measures: We performed a cost-utility analysis of the GoYK intervention, measuring health outcomes in terms of quality-adjusted life years (QALYs) and costs in euros, and extrapolated the results to a lifetime horizon using a Markov model. Subjects: The GoYK study was a quasi-experimental study involving 147 patients with CKD and 48 healthcare professionals from Dutch general practices and nephrology clinics, followed over nine months. Key Results: We found that the GoYK intervention would yield a cost-saving of €28,616 and a gain of 0.37 QALYs per CKD patient across the life course. Moreover, GoYK would avert 31 deaths and 113 new dialyses per 1,000 patients in the first 10 years. These results mainly stemmed from the intervention effect on the transition to end-stage renal disease, where reductions of as little as 1% would already mean GoYK is cost-saving. The intervention remained cost-effective in multiple sensitivity and scenario analyses. Conclusions: GoYK might be a solution to slow CKD progression and, thereby, reduce CKD costs. Given these promising findings and the novelty of our study, further research should confirm our findings before broad implementation.

Introduction: Virtual reality (VR) therapy is increasingly used to mitigate pain and anxiety in inpatient settings, with varying effectiveness in postoperative settings. The costs of VR therapy also differ among suppliers. This health-economic analysis aims to inform policy- and decision-makers on the potential impact of VR therapy from a societal perspective based on pain management at discharge and the development of chronic postsurgical pain (CPSP). Methods: A Markov model was developed to simulate 1-year postoperative costs and effects. Using a threshold and headroom analysis, the Incremental Cost-effectiveness Ratio (ICER) was calculated for various VR effectiveness estimates and costs when VR therapy demonstrated cost-effectiveness or cost-savings for postoperative pain management. VR effectiveness was based on opioid use at discharge, affecting the Markov model’s initial distribution and CPSP development. The ICER was calculated from quality-adjusted life-years (QALYs) and costs associated with CPSP. A univariate sensitivity analysis was used to assess parameter uncertainty by varying each parameter by ±20% from the base-case value. Results: VR therapy needs to reduce opioid use at discharge by at least 2.8% to be cost-effective at a willingness-to-pay threshold of €20 000 per QALY and VR costs of €47.48 per patient. To be cost-saving, a reduction of at least 6.5% is needed. The sensitivity analysis indicated that the transition probability from “pain with opioid” to “pain free” in month 2 had the most impact on the ICER. Other significant variables included VR effectiveness and costs, each influencing the ICER by over €5000. Conclusion: The needed 2.8% reduction in opioid use at discharge seems plausible based on literature. However, knowledge gaps regarding the effectiveness of VR, the incidence of chronic postoperative pain, and societal costs of chronic pain need to be addressed, to better understand VR therapy’s role in optimizing postoperative pain management.

Objective: This study aims to assess the cost-effectiveness of the Fall 2023 COVID-19 mRNA XBB.1.5 vaccination campaign in the Netherlands, comparing the XBB1.5 updated mRNA-1273.222 with the XBB1.5 updated BNT162b2 vaccine. Methods: A one-year decision tree-based cost-effectiveness model was developed, considering three scenarios: no Fall 2023 vaccination, BNT162b2 vaccination and mRNA-1273 vaccination in the COVID-19 high-risk population in the Netherlands. The high-risk population includes everyone of 60 and older, and younger adults at high risk as identified by the Dutch Health Council. Costs were included from a societal perspective and the modelled period started in October 2023 and ended in September 2024, including life years lost with a lifetime horizon. Sensitivity and scenario analyses were conducted to evaluate model robustness. Results: In the base case, mRNA-1273 demonstrated substantial benefits over BNT162b2, potentially averting 20,629 symptomatic cases, 924 hospitalizations (including 32 ICU admissions), 207 deaths, and 2,124 post-COVID cases. Societal cost savings were €12.9million (excluding vaccination costs), with 1,506 QALYs gained. The break-even incremental price of mRNA-1273 compared to BNT162b2 was €16.72 or €34.32 considering a willingness to pay threshold (WTP) of 20,000 or 50,000 euro per QALY gained. Conclusion: This study provides a comprehensive cost-effectiveness analysis supporting the adoption of the mRNA-1273 vaccine in the national immunization programme in the Netherlands, provided that the Dutch government negotiates a vaccine price that is at most €34.32 per dose higher than BNT162b2. Despite limitations, the findings emphasize the substantial health and economic benefits of mRNA-1273 over BNT162b2 in the high-risk population.

Objectives: We perform a cost-effectiveness analysis (CEA) and budget impact analysis (BIA) of baloxavir marboxil compared to current care in the Netherlands for patients at risk of influenza-related complications, including patients with comorbidities and the elderly. Methods: In the CEA, a decision tree model was developed to assess the cost-effectiveness of baloxavir marboxil for a cohort of 52-year-olds from a societal perspective. A lifetime horizon was taken by incorporating the quality-adjusted life expectancy. The BIA included different epidemiological scenarios, estimating different plausible epidemiological scenarios for seasonal influenza considering the whole Dutch population with an increased risk of influenza complications. Results: The base-case ICER was estimated to be €8,300 per QALY. At the willingness-to-pay threshold of €20,000 per QALY, the probability of being cost effective was 58%. The base-case expected budget impact was €5.7 million on average per year, ranging from €1.5 million to €10.5 million based on the severity of the influenza epidemic and vaccine effectiveness. Conclusion: In the Netherlands, baloxavir is a cost-effective treatment option for seasonal influenza, with a base-case ICER of €8,300 per QALY for the population aged 60 years and over and patients at high risk of influenza-related complications. For a large part, this ICER is driven by the reduction of the illness duration of influenza and productivity gains in the working population.

Background: While COVID-19 hospitalization costs are essential for policymakers to make informed health care resource decisions, little is known about these costs in western Europe. The aim of the current study is to analyze these costs for a German setting, track the development of these costs over time and analyze the daily costs. Methods: Administrative costing data was analyzed for 598 non-Intensive Care Unit (ICU) patients and 510 ICU patients diagnosed with COVID-19 at the Frankfurt University hospital. Descriptive statistics of total per patient hospitalization costs were obtained and assessed over time. Propensity scores were estimated for length of stay (LOS) at the general ward and mechanical ventilation (MV) duration, using covariate balancing propensity score for continuous treatment. Costs for each additional day in the general ward and each additional day in the ICU with and without MV were estimated by regressing the total hospitalization costs on the LOS and the presence or absence of several treatments using generalized linear models, while controlling for patient characteristics, comorbidities, and complications. Results: Median total per patient hospitalization costs were €3,010 (Q1 – Q3: €2,224—€5,273), €5,887 (Q1 – Q3: €3,054—€10,879) and €21,536 (Q1 – Q3: €7,504—€43,480), respectively, for non-ICU patients, non-MV and MV ICU patients. Total per patient hospitalization costs for non-ICU patients showed a slight increase over time, while total per patient hospitalization costs for ICU patients decreased over time. Each additional day in the general ward for non-ICU COVID-19 patients costed €463.66 (SE: 15.89). Costs for each additional day in the general ward and ICU without and with mechanical ventilation for ICU patients were estimated at €414.20 (SE: 22.17), €927.45 (SE: 45.52) and €2,224.84 (SE: 70.24). Conclusions: This is, to our knowledge, the first study examining the costs of COVID-19 hospitalizations in Germany. Estimated costs were overall in agreement with costs found in literature for non-COVID-19 patients, except for higher estimated costs for mechanical ventilation. These estimated costs can potentially improve the precision of COVID-19 cost effectiveness studies in Germany and will thereby allow health care policymakers to provide better informed health care resource decisions in the future.