Economic Evaluations of Screening Programs for Chronic Kidney Disease: A Systematic Review.

OBJECTIVES: The aim of this review is to appraise and assimilate evidence from studies that have reported on the cost-effectiveness of screening programs for chronic kidney disease (CKD). METHODS: The study protocol was registered on International Prospective Register of Systematic Reviews (PROSPERO). The final search was conducted on 18 January 2023 using 7 databases. Screening of articles, data extraction, and quality assessment was performed by 2 independent reviewers. The ISPOR-AMCP-NPC checklist was used to assess the credibility of the included studies. RESULTS: From 4948 retrieved studies, a final total of 20 studies were included in the qualitative synthesis. Studies found that screening in diabetic populations was cost-effective (n = 8, 57%) or even cost-saving (n = 6, 43%). Four studies (67%) found that screening in hypertensive populations was also cost-effective. For the general population, findings were inconsistent across studies in which many found screening to be cost-effective (n = 11, 69%), some cost-saving (n = 2, 12%), and others not cost-effective (n = 3, 19%). The most influential parameters identified were prevalence of CKD and cost of screening. CONCLUSIONS: Screening for CKD in patients with diabetes or hypertension is recommended from a cost-effectiveness point of view. For the general population, despite some inconsistent findings, the majority of studies demonstrated that screening in this population is cost-effective, depending mainly on the prevalence and the costs of screening. Healthcare decision makers need to consider the prevalence, stratification strategies, and advocate for lower screening costs to reduce the burden on healthcare budgets and to make screening even more favorable from the health-economic perspective.

Reducing Hospital Capacity Needs for Seasonal Respiratory Infections: The Case of Switching to High-Dose Influenza Vaccine for Dutch Older Adults.

OBJECTIVES: Influenza is responsible for considerable health and economic burden every year. Especially older adults are vulnerable for influenza infection and its complications due to immunosenescence and often-underlying medical conditions. Recently, the innovative quadrivalent high-dose influenza vaccine (QIV-HD) has become available in Europe. Through its enhanced immunogenicity, QIV-HD offers improved protection for older adults against respiratory as well as cardiovascular complications. We estimated the potential impact-specifically in terms of hospital admissions and related costs-of a hypothetical past switch from QIV-Standard dose (SD) to QIV-HD in The Netherlands. METHODS: Estimates of hospitalizations for the older adults vaccinated with QIV-SD were derived from the seasons 2010/2011-2017/2018. Subsequently, the number of respiratory infections and cardiovascular complications of influenza were estimated for the year 2019/2020 for both QIV-SD and QIV-HD. To calculate the overall corresponding savings, costs for hospital complications, derived from literature, were used. RESULTS: When QIV-HD would have been used instead of QIV-SD during the season 2019/2020, an additional 220 hospitalizations would have been averted among older adults of 60 years and older in the Netherlands. This corresponds to savings of €1 219 779 (uncertainty interval: 1 089 813-1 348 549), of which 69% is attributable to cardiovascular-related hospitalizations. CONCLUSIONS: We demonstrate that a relevant improvement in influenza vaccination among older adults in The Netherlands can be achieved by switching from the current QIV-SD to QIV-HD. Not only comes a switch from QIV-SD to QIV-HD with a significant reduction in pressure on hospital capacity but also with notable cost savings.

The Effect of the Drug Life Cycle Price on Cost-Effectiveness: Case Studies Using Real-World Pricing Data.

OBJECTIVES: Cost-effectiveness analyses (CEAs) generally assume constant drug prices throughout the model time horizon, yet it is known that prices are not constant, often with price decreases near loss of exclusivity (LOE). This study explores the impact of using dynamic drug-specific prices on the incremental cost-effectiveness ratio (ICER) using selected reproduced case studies. METHODS: Case studies were selected following explicit criteria to reflect a variety of drug characteristics. For each drug, a published CEA model was identified, replicated, and modified with dynamic real-world pricing data, to compare ICERs based on constant drug prices with estimates obtained when including drug life cycle pricing. The impact of dynamic real-world pricing-inclusive LOE-was analyzed using a single patient cohort and multiple cohorts over time. RESULTS: Fluvastatin, alendronic acid + colecalciferol combination therapy, letrozole and clopidogrel were selected as case studies. Inclusion of real-world pricing data compared with applying constant prices reduced the ICER in a single-cohort setting up to 43%. In the multicohort analyses, further reductions of the ICERs were observed of up to 113%. The ICERs were sensitive to the period of drug usage relative to the models' time horizons, the relative proportions of drug costs in the overall treatment costs, and timing of LOE compared with the cost year of the original analysis. CONCLUSIONS: Assuming dynamic drug prices may lead to more representative ICER estimates. Future CEAs for drugs could account for predicted and disaggregated life cycle price developments based on retrospective data.

Psychometric properties of kidney disease quality of life-36 (KDQOL-36) in dialysis patients in Indonesia.

OBJECTIVE: The study aimed to evaluate the psychometric properties of KDQOL-36 Bahasa Indonesia in hemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD) patients in Indonesia. METHODS: The psychometric analysis was conducted in three hospitals offering both HD and CAPD. The validity was assessed through structural, convergent, and known-group validity, while reliability was evaluated using internal consistency and test-retest reliability. RESULTS: The study involved 370 participants of which 71% received HD treatment. No floor and ceiling effects (< 10%) were identified. Confirmatory factor analysis supported a good model fit for both generic and kidney-specific domains, while exploratory factor analysis revealed three factors for kidney-specific domains and only three items with a loading factor below 0.4. Convergent validity showed positive correlations between kidney-specific domains, generic domains, and EQ-5D. The comparison of quality of life among subgroups based on dialysis type and whether or not patients had diabetes supported the hypotheses of known-group validity. Cronbach's alpha and omega values had demonstrated good internal consistency. Test-retest reliability indicated burden of kidney disease had good reliability, while other domains had moderate reliability. CONCLUSION: The study supports the validity and reliability of both generic and kidney-specific domains of KDQOL-36 Bahasa Indonesia to evaluate quality of life in patients with HD and CAPD in Indonesia. As health-related quality of life is a crucial predictor of patient outcomes, this report contributes new evidence about validity and reliability to recommend the use of KDQOL-36 Bahasa Indonesia in dialysis centers.

A Genotype-Guided Strategy for Oral P2Y12 Inhibitors in Primary PCI.

BACKGROUND: It is unknown whether patients undergoing primary percutaneous coronary intervention (PCI) benefit from genotype-guided selection of oral P2Y12 inhibitors. METHODS: We conducted a randomized, open-label, assessor-blinded trial in which patients undergoing primary PCI with stent implantation were assigned in a 1:1 ratio to receive either a P2Y12 inhibitor on the basis of early CYP2C19 genetic testing (genotype-guided group) or standard treatment with either ticagrelor or prasugrel (standard-treatment group) for 12 months. In the genotype-guided group, carriers of CYP2C19*2 or CYP2C19*3 loss-of-function alleles received ticagrelor or prasugrel, and noncarriers received clopidogrel. The two primary outcomes were net adverse clinical events - defined as death from any cause, myocardial infarction, definite stent thrombosis, stroke, or major bleeding defined according to Platelet Inhibition and Patient Outcomes (PLATO) criteria - at 12 months (primary combined outcome; tested for noninferiority, with a noninferiority margin of 2 percentage points for the absolute difference) and PLATO major or minor bleeding at 12 months (primary bleeding outcome). RESULTS: For the primary analysis, 2488 patients were included: 1242 in the genotype-guided group and 1246 in the standard-treatment group. The primary combined outcome occurred in 63 patients (5.1%) in the genotype-guided group and in 73 patients (5.9%) in the standard-treatment group (absolute difference, -0.7 percentage points; 95% confidence interval [CI], -2.0 to 0.7; P<0.001 for noninferiority). The primary bleeding outcome occurred in 122 patients (9.8%) in the genotype-guided group and in 156 patients (12.5%) in the standard-treatment group (hazard ratio, 0.78; 95% CI, 0.61 to 0.98; P = 0.04). CONCLUSIONS: In patients undergoing primary PCI, a CYP2C19 genotype-guided strategy for selection of oral P2Y12 inhibitor therapy was noninferior to standard treatment with ticagrelor or prasugrel at 12 months with respect to thrombotic events and resulted in a lower incidence of bleeding. (Funded by the Netherlands Organization for Health Research and Development; POPular Genetics ClinicalTrials.gov number, NCT01761786; Netherlands Trial Register number, NL2872.).

Cost-Effectiveness of Newborn Screening for Spinal Muscular Atrophy in The Netherlands.

OBJECTIVES: Spinal muscular atrophy (SMA) is a rare genetic disorder that causes progressive muscle weakness and paralysis. In its most common and severe form, the majority of untreated infants die before 2 years of age. Early detection and treatment, ideally before symptom onset, maximize survival and achievement of age-appropriate motor milestones, with potentially substantial impact on health-related quality of life. Therefore, SMA is an ideal candidate for inclusion in newborn screening (NBS) programs. We evaluated the cost-effectiveness of including SMA in the NBS program in The Netherlands. METHODS: We developed a cost-utility model to estimate lifetime health effects and costs of NBS for SMA and subsequent treatment versus a treatment pathway without NBS (ie, diagnosis and treatment after presentation with overt symptoms). Model inputs were based on literature, local data, and expert opinion. Sensitivity and scenario analyses were conducted to assess model robustness and validity of results. RESULTS: After detection of SMA by NBS in 17 patients, the number of quality-adjusted life-years gained per annual birth cohort was estimated at 320 with NBS followed by treatment compared with treatment after clinical SMA diagnosis. Total healthcare costs, including screening, diagnostics, treatment, and other healthcare resource use, were estimated to be €12 014 949 lower for patients identified by NBS. CONCLUSIONS: NBS for early identification and treatment of SMA versus later symptomatic treatment after clinical diagnosis improves health outcomes and is less costly and, therefore, is a cost-effective use of resources. Results were robust in sensitivity and scenario analyses.

Increasing the information provided by probabilistic sensitivity analysis: The relative density plot.

BACKGROUND: Results of probabilistic sensitivity analyses (PSA) are frequently visualized as a scatterplot, which is limited through overdrawing and a lack of insight in relative density. To overcome these limitations, we have developed the Relative Density plot (PSA-ReD). METHODS: The PSA-ReD combines a density plot and a contour plot to visualize and quantify PSA results. Relative density, depicted using a color gradient, is transformed to a cumulative probability. Contours are then plotted over regions with a specific cumulative probability. We use two real-world case studies to demonstrate the value of the PSA-ReD plot. RESULTS: The PSA-ReD method demonstrates proof-of-concept and feasibility. In the real-world case-studies, PSA-ReD provided additional visual information that could not be understood from the traditional scatterplot. High density areas were identified by color-coding and the contour plot allowed for quantification of PSA iterations within areas of the cost-effectiveness plane, diminishing overdrawing and putting infrequent iterations in perspective. Critically, the PSA-ReD plot informs modellers about non-linearities within their model. CONCLUSIONS: The PSA-ReD plot is easy to implement, presents more of the information enclosed in PSA data, and prevents inappropriate interpretation of PSA results. It gives modelers additional insight in model functioning and the distribution of uncertainty around the cost-effectiveness estimate.

Antivirals to prepare for surges in influenza cases: an economic evaluation of baloxavir marboxil for the Netherlands.

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.

Cost-effectiveness of high-dose influenza vaccination in the Netherlands: Incorporating the impact on both respiratory and cardiovascular hospitalizations.

OBJECTIVES: We assess the cost-effectiveness of switching from standard-dose quadrivalent influenza vaccination (SD-QIV) to high-dose vaccination (HD-QIV) for Dutch adults aged 60 years and older. METHODS: A health-economic model was used to compare the scenario where HD-QIV was implemented compared to the current standard, SD-QIV. This model used a lifetime horizon and assessed the cost-effectiveness from a societal perspective. A recently published meta-analysis was used to incorporate the benefits of HD-QIV, including cardiorespiratory hospitalizations, in analyses considering RCT only or combining RCT and RWE estimates in a scenario analysis. RESULTS: Implementing HD-QIV is cost effective at its list price, with an ICER of €5,400 per QALY gained. The main driver of these results is the prevention of cardiorespiratory hospitalizations. Other public health benefits are the prevention of GP consults and deaths. HD-QIV is highly likely to be cost-effective, reaching a 100% probability of being cost effective at the Dutch willingness-to-pay threshold of €20,000 per QALY. CONCLUSIONS: Implementing HD-QIV for adults aged 60 and over within the existing influenza vaccination campaign is highly cost effective. HD-QIV may support alleviating potential capacity issues in Dutch hospitals in the winter respiratory season.

Inter-reviewer reliability of human literature reviewing and implications for the introduction of machine-assisted systematic reviews: a mixed-methods review.

OBJECTIVES: Our main objective is to assess the inter-reviewer reliability (IRR) reported in published systematic literature reviews (SLRs). Our secondary objective is to determine the expected IRR by authors of SLRs for both human and machine-assisted reviews. METHODS: We performed a review of SLRs of randomised controlled trials using the PubMed and Embase databases. Data were extracted on IRR by means of Cohen's kappa score of abstract/title screening, full-text screening and data extraction in combination with review team size, items screened and the quality of the review was assessed with the A MeaSurement Tool to Assess systematic Reviews 2. In addition, we performed a survey of authors of SLRs on their expectations of machine learning automation and human performed IRR in SLRs. RESULTS: After removal of duplicates, 836 articles were screened for abstract, and 413 were screened full text. In total, 45 eligible articles were included. The average Cohen's kappa score reported was 0.82 (SD=0.11, n=12) for abstract screening, 0.77 (SD=0.18, n=14) for full-text screening, 0.86 (SD=0.07, n=15) for the whole screening process and 0.88 (SD=0.08, n=16) for data extraction. No association was observed between the IRR reported and review team size, items screened and quality of the SLR. The survey (n=37) showed overlapping expected Cohen's kappa values ranging between approximately 0.6-0.9 for either human or machine learning-assisted SLRs. No trend was observed between reviewer experience and expected IRR. Authors expect a higher-than-average IRR for machine learning-assisted SLR compared with human based SLR in both screening and data extraction. CONCLUSION: Currently, it is not common to report on IRR in the scientific literature for either human and machine learning-assisted SLRs. This mixed-methods review gives first guidance on the human IRR benchmark, which could be used as a minimal threshold for IRR in machine learning-assisted SLRs. PROSPERO REGISTRATION NUMBER: CRD42023386706.

Cost of Illness Analysis of Invasive Meningococcal Disease Caused by Neisseria Meningitidis Serogroup B in the Netherlands-a Holistic Approach.

INTRODUCTION: Invasive meningococcal disease (IMD) caused by Neisseria meningitidis is a rapidly progressing, rare disease that often presents as meningitis or sepsis. It mostly affects infants and adolescents, with high fatality rates or long-term sequelae. In the Netherlands, serogroup B (MenB) is most prevalent. We aimed to estimate the economic burden of MenB-related IMD between 2015 and 2019, including direct and indirect medical costs from short- and long-term sequelae, from a societal perspective. METHODS: IMD incidence was based on laboratory-based case numbers from the Netherlands Reference Laboratory for Bacterial Meningitis (Amsterdam UMC, Amsterdam, the Netherlands); there were 74 MenB cases on average per year in the study period 2015-2019. Case-fatality rate (3.8%) and percentage of patients discharged with sequelae (46%) were derived from literature. Direct costs included treatment costs of the acute phase, long-term sequelae, and public health response. Indirect costs were calculated using the human capital (HCA) and friction costs (FCA) approaches, in which productivity losses were estimated for patients and parents during the acute and sequelae phases. Costs were discounted by 4% yearly. RESULTS: Estimated costs due to MenB IMD in an annual cohort were €3,094,199 with FCA and €9,480,764 with HCA. Direct costs amounted to €2,974,996, of which 75.2% were related to sequelae. Indirect costs related to sequelae were €52,532 with FCA and €5,220,398 with HCA. CONCLUSION: Our analysis reflects the high economic burden of MenB-related IMD in the Netherlands. Sequelae costs represent a high proportion of the total costs. Societal costs were dependent on the applied approach (FCA or HCA).

Cost-Effectiveness of Test-and-Treat Strategies to Reduce the Antibiotic Prescription Rate for Acute Febrile Illness in Primary Healthcare Clinics in Africa.

BACKGROUND: Inappropriate antibiotic use increases selective pressure, contributing to antimicrobial resistance. Point-of-care rapid diagnostic tests (RDTs) would be instrumental to better target antibiotic prescriptions, but widespread implementation of diagnostics for improved management of febrile illnesses is limited. OBJECTIVE: Our study aims to contribute to evidence-based guidance to inform policymakers on investment decisions regarding interventions that foster more appropriate antibiotic prescriptions, as well as to address the evidence gap on the potential clinical and economic impact of RDTs on antibiotic prescription. METHODS: A country-based cost-effectiveness model was developed for Burkina Faso, Ghana and Uganda. The decision tree model simulated seven test strategies for patients with febrile illness to assess the effect of different RDT combinations on antibiotic prescription rate (APR), costs and clinical outcomes. The incremental cost-effectiveness ratio (ICER) was expressed as the incremental cost per percentage point (ppt) reduction in APR. RESULTS: For Burkina Faso and Uganda, testing all patients with a malaria RDT was dominant compared to standard-of-care (SoC) (which included malaria testing). Expanding the test panel with a C-reactive protein (CRP) test resulted in an ICER of $ 0.03 and $ 0.08 per ppt reduction in APR for Burkina Faso and Uganda, respectively. For Ghana, the pairwise comparison with SoC-including malaria and complete blood count testing-indicates that both testing with malaria RDT only and malaria RDT + CRP are dominant. CONCLUSION: The use of RDTs for patients with febrile illness could effectively reduce APR at minimal additional costs, provided diagnostic algorithms are adhered to. Complementing SoC with CRP testing may increase clinicians' confidence in prescribing decisions and is a favourable strategy.

Cost-effectiveness of home-based screening of the general population for albuminuria to prevent progression of cardiovascular and kidney disease.

Background: Chronic kidney disease (CKD) is often detected late, leading to substantial health loss and high treatment costs. Screening the general population for albuminuria identifies individuals at high risk of kidney events and cardiovascular disease (CVD) who may benefit from early start of preventive interventions. Previous studies on the cost-effectiveness of albuminuria population screening were inconclusive, but were based on survey or cohort data rather than an implementation study, modelled screening as performed by general practitioners rather than home-based screening, and often included only benefits with respect to kidney events. We evaluated the cost-effectiveness of home-based general population screening for increased albuminuria based on real-world data obtained from a prospective implementation study taking into account prevention of CKD as well as CVD events. Methods: We developed an individual-level simulation model to compare home-based screening using a urine collection device with usual care (no home-based screening) in individuals of the general population aged 45-80, based on the THOMAS study (Towards HOMe-based Albuminuria Screening). Cost-effectiveness was assessed from the Dutch healthcare perspective with a lifetime horizon. The costs of the screening process and benefits of preventing CKD progression (dialysis and kidney transplantation) and CVD events (non-fatal myocardial infarction, non-fatal stroke, fatal CVD event) were reflected. Albuminuria detection led to treatment of identified risk factors. The model subsequently simulated CKD progression, the occurrence of CVD events, and death. The risks of experiencing CVD events were calculated using the SCORE2 CKD risk prediction model and individual-level data from the THOMAS study. Relative treatment effectiveness, quality of life scores, resource use, and cost inputs were obtained from literature. Model outcomes were the number of CKD and CVD-related events, total costs, quality-adjusted life years (QALYs), and the incremental cost-effectiveness ratio (ICER) per QALY gained by screening versus usual care. All results were obtained through probabilistic analysis. Findings: The absolute difference between screening versus usual care in lifetime probability of dialysis, kidney transplantation, non-fatal myocardial infarction, non-fatal stroke, and fatal CVD events were 0.2%, 0.05%, 0.6%, 0.6%, and 0.2%, respectively. This led to relative decreases compared to usual care in lifetime incidence of these events of 10.7%, 11.1%, 5.1%, 4.1%, and 1.6%, respectively. The incremental costs and QALYs of screening were €1607 and 0.17 QALY, respectively, which led to a corresponding ICER of €9225/QALY. The probability of screening being cost-effective for the Dutch willingness-to-pay threshold for preventive population screening of €20,000/QALY was 95.0%. Implementing the screening in the subgroup of 45-64 years old reduced the ICER (€7946/QALY), whereas implementing screening in the subgroup of 65-80 years old increased the ICER (€10,310/QALY). A scenario analysis assuming treatment optimization in all individuals with newly diagnosed risk factors or known risk factors not within target range reduced the ICER to €7083/QALY, resulting from the incremental costs and QALY gain of €2145 and 0.30, respectively. Interpretation: Home-based screening for increased albuminuria to prevent CVD and CKD events is likely cost-effective. More health benefits can be obtained by screening younger individuals and better optimization of care in individuals identified with newly diagnosed or known risk factors outside target range. Funding: Dutch Kidney Foundation, Top Sector Life Sciences & Health of the Dutch Ministry of Economic Affairs.

Budget and health impact of switching eligible patients with atrial fibrillation to lower- dose dabigatran.

Objectives: To assess the comparative budget and health impact of lower-dose dabigatran versus reduced doses of apixaban and rivaroxaban in atrial fibrillation (AF) patients eligible for a lower-/reduced-dose due to individual patient characteristics in the Netherlands. Methods: A budget impact model was developed in accordance with ISPOR guidelines. A 3-year-time horizon was considered, and analyses were conducted from a Dutch healthcare payer's perspective. The model applies published data to local AF-epidemiology, allowing calculations to estimate clinical events (strokes and haemorrhages) and costs. The analyses were based on real-world outcomes from patients with AF receiving a first direct oral anticoagulant (DOAC) prescription for low-dose dabigatran (110 mg) and a reduced dose of apixaban (2.5 mg) or rivaroxaban (15 mg). Two situations of switching treatments from one to another DOAC were modelled: switching from apixaban to dabigatran and from rivaroxaban to dabigatran. Base case results were given as savings per 100 patient-year, per total Dutch population, and events avoided. A univariate sensitivity analysis was conducted to explore the uncertainty around epidemiological and event costs input data. Scenario analyses were performed to estimate the effect of different market shares and potential price reductions due to future patent expiry for the total real-world population from the Netherlands. Results: The 3-years outcomes of switching patients eligible for a lower-/reduced-dose due to individual patient characteristics from apixaban or rivaroxaban to dabigatran resulted in cost savings estimated at €157 or €72 thousand per 100 patient-years, respectively, or €146 million per total Dutch population. Looking into the clinical events, dabigatran reflected the lowest number of mortalities, ischemic strokes, major bleeding, non-major bleeding, and haemorrhagic stroke compared to apixaban and rivaroxaban. The sensitivity analysis consistently reflected cost savings, with the ischeamic stroke events having the biggest impact. Accounting for the Dutch situation, both scenarios showed total savings ranging from €45 to €229 million over 3 years. Conclusions: Switching eligible AF-patients from reduced-dose apixaban or rivaroxaban to lower-dose dabigatran has the potential to reduce healthcare payer's budget expenditures and provide health gains. Cost savings can potentially be further enhanced by market share adjustments and further price reductions.

Rationale and development of an e-health application to deliver patient-centered care during treatment for recently diagnosed multiple myeloma patients: pilot study of the MM E-coach.

BACKGROUND: Patients with multiple myeloma (MM) increasingly face complicated treatment regimens. E-health may support patients and healthcare providers in enhancing a patient-centered healthcare approach. Therefore, we aimed to develop a patient-centered multi-modality e-health application, to assess the application for usability and end-user experiences. METHODS: The application was developed following an iterative "action-based" methodology using the design thinking approach. Key end users participated, and relevant stakeholders were consulted in the development process. First, the care pathway was evaluated, the focus of development was determined, and a solution ideated during recurring multidisciplinary meetings. Second, a prototype was tested and improved. Third, a subsequent prototype was evaluated during a pilot study with patients and healthcare professionals on usability, usage, and experiences. RESULTS: The multi-modality application, named the "MM E-coach," consisted of a newly developed medication module, patient-reported outcome (PRO) questionnaire assessments, a messaging service, alerts, information provision, and a personal care plan. The median system usability score was 60 on a scale of 0-100. Patients appreciated the medication overview, healthcare professionals appreciated the outpatient clinic preparation module, and both appreciated the messaging service. Additional recommendations for improvement mostly revolved around the flexibility of functionalities and look and feel of the application. CONCLUSIONS: The MM E-coach has the potential to provide patient-centered care by supporting patients and caregivers during MM treatment and is a promising application to be implemented in the MM care pathway. A randomized clinical trial was initiated to study its clinical effectiveness.

An Updated Analysis of the Impact of HPV Vaccination Based on Long-term Effectiveness in the Netherlands.

INTRODUCTION: Vaccination against human papillomavirus (HPV) is considered the most effective strategy to protect women from cervical cancer. Three HPV vaccines are currently licensed in Europe and, although they are generally supported by favorable health economic outcomes, current models fall short in predicting vaccination benefits. Here, we aim to re-evaluate the health benefits of HPV vaccination, using updated long-term effectiveness data and emphasizing quality of life losses related to pre-cancer disease and treatment. METHODS: We used a static Markov model that compared "only screening" (includes unvaccinated girls) and "vaccination" (assumes 100% vaccination coverage with the bivalent HPV vaccine). A lifetime cohort of 100,000 uninfected 12-year-old girls was included, in which the number of cases with cervical intraepithelial neoplasia grade 2 or higher/3 (CIN2+, CIN3), cervical cancer, and cervical cancer deaths per scenario were determined. Furthermore, the reduction in major excisional procedures, the preterm deliveries averted, and the related gain in quality-adjusted life years (QALYs) due to vaccination were estimated. RESULTS: The bivalent vaccine showed larger reductions in CIN2+, CIN3, cervical cancer cases, cervical cancer deaths, and major excisional treatments, after including long-term efficacy and effectiveness data, compared to previous data. Moreover, we observed an increased amount of QALYs gained due to prevention of major excisional treatment and the negative side effects related to it. CONCLUSIONS: Updated health economic models for HPV vaccination, using updated and long-term effectiveness data and including prevention of treatment-related side effects, demonstrate a substantial additional positive effect on vaccination outcomes. Indeed, extrapolation of the bivalent HPV vaccine's updated long-term effectiveness data against HPV-related cervical diseases shows that the positive effects of vaccination may be more substantial than previously estimated. There is a graphical abstract available for this article.

Cervical cancer is one of the most common cancers among women, and the most effective strategy for its prevention is vaccination against HPV infection. Several studies have predicted the benefits of vaccination; however, most of them fall short due to a lack of long-term data and treatment impact. The aim of this study is to re-evaluate the benefits of vaccination with the bivalent vaccine in the Netherlands using updated longer-term data and benefits from preventing treatment.We used a cost-effectiveness model to compare two scenarios: only screening and vaccination plus screening. We included 100,000 12-year-old girls in the model and compared the following outcomes: number of individuals with benign cervical lesions, number of individuals with cervical cancer, number of deaths, reduction in treatment after vaccination, premature births avoided after vaccination, and quality of life gains.We found that the bivalent vaccine showed larger reductions in pre-cancerous lesions (CIN2+, CIN3), cervical cancer cases, cervical cancer deaths, and major excisional treatments, compared to the results of previously published cost-effectiveness analyses when new longer-term data were included. The prevention of treatment for the lesions represents a significant added value for vaccination.Our modeling study confirms the protective effect of the bivalent vaccine on cervical cancer. Moreover, it reflects a substantial additional value of vaccination compared to the benefits of vaccination that have been shown before.

Value-based health care in Western countries: a scoping review on the implementation of patient-reported-outcomes sets for hospital-based interventions.

INTRODUCTION: For implementation of the value-based health-care (VBHC) concept, use of patient-reported outcome measures (PROMs), patient-reported experience measures (PREMs), and clinical outcomes is crucial. The aim of this study was to summarize published studies on implemented PROMs, PREMs, and clinical-outcomes sets in health-care practice. AREAS COVERED: A scoping review was conducted by using PubMed and Embase. Our study focused on implementation examples of patient-reported outcome sets in Western countries' hospitals. Included papers were analyzed on content, in particular concerning PROMs, PREMs, and clinical outcomes. We also assessed differences between diseases, categorized as patient-reported outcomes in curative, chronic, and palliative treatments in the hospital. EXPERT OPINION: A total of 20 studies were found that presented VBHC implementation examples. Results illustrate the disconnection between the development of PROMs and PREMs and the implementation phase, with implementation still in infancy. Hospital organizations should enhance organization for the implementation of VBHC. It is crucial that leading examples of successful VBHC serve as blueprints for implementation, with the participation of all relevant stakeholders. Affordability and sustainability of health care can be enhanced by scaling up successful VBHC-interventions on population levels.

Investing in the Prevention of Communicable Disease Outbreaks: Fiscal Health Modelling-The Tool of Choice for Assessing Public Finance Sustainability.

National strategies for preparedness for future outbreaks of COVID-19 often include timely preparedness with vaccines. Fiscal health modelling (FHM) has recently been brought forward as an additional analysis by defining the public economic impact from a governmental perspective. As governments are the main decision-makers concerning pandemic preparedness, this study aimed to develop an FHM framework for infectious diseases in the Netherlands. Based on the Dutch COVID-19 outbreak of 2020 and 2021 and publicly available data on tax income and gross domestic product (GDP), the fiscal impact of COVID-19 was assessed using two approaches. Approach I: Prospective modelling of future fiscal impact based on publicly available laboratory-confirmed COVID-19 cases; and Approach II: Retrospective assessment of the extrapolated tax and benefit income and GDP. Approach I estimated the consequences that can be causally linked to the population counts reducing income taxes by EUR 266 million. The total fiscal loss amounted to EUR 164 million over 2 years (excluding pension payments averted). The total losses in terms of tax income (2020 and 2021) and GDP (2020) (Approach II), were estimated at, respectively, EUR 13.58 billion and EUR 96.3 billion. This study analysed different aspects of a communicable disease outbreak and its influence on government public accounts. The choice of the two presented approaches depends on the perspective of the analysis, the time horizon of the analysis and the availability of data.