Real-world healthcare costs of localized and regionally advanced cutaneous melanoma in the Netherlands.

The aim of this study was to provide insight into real-world healthcare costs of patients initially diagnosed with localized or regionally advanced melanoma in three Dutch hospitals between 2003 and 2011. Patients were stratified according to their stage at diagnosis and recurrence status. Costs were calculated by applying unit costs to individual patient resource use and reported for the full disease course, the initial treatment episode, and treatment episodes for disease recurrence (stratified by type of recurrence). We included 198 patients with localized melanoma and 98 patients with regionally advanced melanoma. Total costs were much higher for patients with disease recurrence than for patients without disease recurrence: €20 007 versus €3032 for patients with localized melanoma and €19 519 versus €5951 for patients with regionally advanced melanoma. This was owing to the costs of disease recurrence because the costs of the initial treatment were comparable between patients with and without disease recurrence. Costs of disease recurrence were dependent on the type of recurrence: €4414, €4604, €8129 and €10 393 for a local recurrence, intralymphatic metastases, regional lymph node metastases and distant metastases, respectively. In conclusion, healthcare costs of patients with localized and regionally advanced melanoma were rather low for the initial treatment. Costs became, however, more substantial in case of disease recurrence. In the context of a rapidly changing treatment paradigm, it remains crucial to monitor treatment outcomes as well as healthcare expenditures.

Cost-effectiveness of Novel Treatment Sequences for Transplant-Ineligible Patients With Multiple Myeloma.

Importance: Although the number of treatments for elderly patients with non-transplant-eligible (NTE) multiple myeloma (MM) has increased substantially, evidence is lacking on the clinical effectiveness and cost-effectiveness of novel treatment sequences. Objective: To determine the optimal sequence of treatment for patients with NTE MM from the perspective of the patient, physician, and society. Design, Setting, and Participants: Using data from a Dutch observational registry, this economic evaluation combined evidence from network meta-analyses in a patient-level simulation model and modeled time-to-event and types of events from a hospital perspective with a lifetime horizon. Data analysis was performed from June 2019 to September 2020. Interventions: Thirty treatment sequences, including up to 3 lines of therapy, were compared with bortezomib-melphalan-prednisone (VMP)-lenalidomide-dexamethasone (LenDex)-pomalidomide-dexamethasone (PomDex). Main Outcomes and Measures: The primary outcomes of the model were overall survival (OS), quality-adjusted life-years (QALYs), costs, and cost-effectiveness. Results: Sequences starting with daratumumab-VMP (second line: carfilzomib-lenalidomide-dexamethasone or elotuzumab-lenalidomide-dexamethasone) or bortezomib-melphalan-prednisone-thalidomide-maintenance bortezomib-thalidomide (VMPT-VT) (second line: daratumumab-lenalidomide-dexamethasone) had the largest expected OS (7.5 years), which is 3.5 additional life-years compared with VMP-LenDex-PomDex. Total costs per patient for these sequences ranged between $786 024 and $1 085 794. The sequence VMPT-VT-carfilzomib-lenalidomide-dexamethasone-panobinostat-bortezomib-dexamethasone had the most favorable cost-effectiveness ratio ($98 585 per life-year gained and $132 707 per QALY gained vs VMP-LenDex-PomDex). Conclusions and Relevance: These findings suggest that sequences including novel treatments were highly effective, but the cost-effectiveness ratios were above currently accepted willingness-to-pay thresholds. Treating MM with novel agents necessitates either a large increase in budget or a substantial reduction of drug costs by price negotiations, and these findings can support these reimbursement decisions and price negotiations.

Healthcare Costs of Metastatic Cutaneous Melanoma in the Era of Immunotherapeutic and Targeted Drugs.

Immunotherapeutic and targeted drugs improved survival of patients with metastatic melanoma. There is, however, a lack of evidence regarding their healthcare costs in clinical practice. The aim of our study was to provide insight into real-world healthcare costs of patients with metastatic cutaneous melanoma. Data were obtained from the Dutch Melanoma Treatment Registry for patients who were registered between July 2012 and December 2018. Mean total/monthly costs per patient were reported for all patients, patients who did not receive systemic therapy, and patients who received systemic therapy. Furthermore, mean episode/monthly costs per line of therapy and drug were reported for patients who received systemic therapy. Mean total/monthly costs were € 89,240/€ 6809: € 7988/€ 2483 for patients who did not receive systemic therapy (n = 784) and € 105,078/€ 7652 for patients who received systemic therapy (n = 4022). Mean episode/monthly costs were the highest for nivolumab plus ipilimumab (€ 79,675/€ 16,976), ipilimumab monotherapy (€ 79,110/€ 17,252), and dabrafenib plus trametinib (€ 77,053/€ 12,015). Dacarbazine yielded the lowest mean episode/monthly costs (€ 6564/€ 2027). Our study showed that immunotherapeutic and targeted drugs had a large impact on real-world healthcare costs. As new drugs continue entering the treatment landscape for (metastatic) melanoma, it remains crucial to monitor whether the benefits of these drugs outweigh their costs.

Potential cost savings owing to the route of administration of oncology drugs: a microcosting study of intravenous and subcutaneous administration of trastuzumab and rituximab in the Netherlands.

There is little evidence on the costs associated with the route of administration of oncology drugs. We investigated time and resource use for hospitals and patients and compared healthcare and societal costs for intravenous (IV) and subcutaneous (SC) administration of trastuzumab and rituximab. Data for the preparation and administration of both drugs were collected at the hospital pharmacy and at the oncology day care unit. Patients completed a questionnaire for obtaining information on societal costs (productivity losses, informal care and traveling expenses). A total of 126 patients were recruited in six hospitals; 82 received trastuzumab (37 IV and 45 SC) and 44 received rituximab (23 IV and 21 SC). The costs per administration (including societal cost but excluding drug costs) were &OV0556;167 and &OV0556;264 for IV and &OV0556;76 and &OV0556;146 for SC trastuzumab and rituximab, respectively. The costs for SC administration were lower in all categories. The largest cost component was related to time spent at the day care unit (overhead costs). This resulted in savings of &OV0556;47 for SC trastuzumab and &OV0556;69 for SC rituximab. The costs related to time of healthcare professionals was &OV0556;9 lower for both drugs. The costs for consumables resulted in another &OV0556;12 savings. Societal costs were &OV0556;22 lower for SC trastuzumab and &OV0556;28 lower for SC rituximab. Although administration costs are relatively a small part of the total costs, important savings can be generated by switching to an SC route of administration especially because a large number of patients receive oncology drugs and patients receive more than one administration.

Real-world healthcare costs of ipilimumab in patients with advanced cutaneous melanoma in The Netherlands.

There is limited evidence on the costs associated with ipilimumab. We investigated healthcare costs of all Dutch patients with advanced cutaneous melanoma who were treated with ipilimumab. Data were retrieved from the nation-wide Dutch Melanoma Treatment Registry. Costs were determined by applying unit costs to individual patient resource use. A total of 807 patients who were diagnosed between July 2012 and July 2015 received ipilimumab in Dutch practice. The mean (median) episode duration was 6.27 (4.61) months (computed from the start of ipilimumab until the start of a next treatment, death, or the last date of follow-up). The average total healthcare costs amounted to &OV0556;81 484, but varied widely (range: &OV0556;18 131-&OV0556;160 002). Ipilimumab was by far the most important cost driver (&OV0556;73 739). Other costs were related to hospital admissions (&OV0556;3323), hospital visits (&OV0556;1791), diagnostics and imaging (&OV0556;1505), radiotherapy (&OV0556;828), and surgery (&OV0556;297). Monthly costs for resource use other than ipilimumab were &OV0556;1997 (SD: &OV0556;2629). Treatment-naive patients (n=344) had higher total costs compared with previously-treated patients (n=463; &OV0556;85 081 vs. &OV0556;78 811). Although patients with colitis (n=106) had higher costs for resource use other than ipilimumab (&OV0556;11 426) compared with patients with other types of immune-related adverse events (n=90; &OV0556;9850) and patients with no immune-related adverse event (n=611; &OV0556;6796), they had lower total costs (&OV0556;76 075 vs. &OV0556;87 882 and &OV0556;81 480, respectively). In conclusion, this nation-wide study provides valuable insights into the healthcare costs of advanced cutaneous melanoma patients who were treated with ipilimumab in clinical practice. Most of the costs were attributable to ipilimumab, but the costs and its distribution varied considerably across subgroups.

The increasing importance of a continence nurse specialist to improve outcomes and save costs of urinary incontinence care: an analysis of future policy scenarios.

BACKGROUND: In an ageing population, it is inevitable to improve the management of care for community-dwelling elderly with incontinence. A previous study showed that implementation of the Optimum Continence Service Specification (OCSS) for urinary incontinence in community-dwelling elderly with four or more chronic diseases results in a reduction of urinary incontinence, an improved quality of life, and lower healthcare and lower societal costs. The aim of this study was to explore future consequences of the OCSS strategy of various healthcare policy scenarios in an ageing population. METHODS: We adapted a previously developed decision analytical model in which the OCSS new care strategy was operationalised as the appointment of a continence nurse specialist located within the general practice in The Netherlands. We used a societal perspective including healthcare costs (healthcare providers, treatment costs, insured containment products, insured home care), and societal costs (informal caregiving, containment products paid out-of-pocket, travelling expenses, home care paid out-of-pocket). All outcomes were computed over a three-year time period using two different base years (2014 and 2030). Settings for future policy scenarios were based on desk-research and expert opinion. RESULTS: Our results show that implementation of the OSCC new care strategy for urinary incontinence would yield large health gains in community dwelling elderly (2030: 2592-2618 QALYs gained) and large cost-savings in The Netherlands (2030: health care perspective: €32.4 Million - €72.5 Million; societal perspective: €182.0 Million - €250.6 Million). Savings can be generated in different categories which depends on healthcare policy. The uncertainty analyses and extreme case scenarios showed the robustness of the results. CONCLUSIONS: Implementation of the OCSS new care strategy for urinary incontinence results in an improvement in the quality of life of community-dwelling elderly, a reduction of the costs for payers and affected elderly, and a reduction in time invested by carers. Various realistic policy scenarios even forecast larger health gains and cost-savings in the future. More importantly, the longer the implementation is postponed the larger the savings foregone. The future organisation of healthcare affects the category in which the greatest savings will be generated.

Balancing the Optimal and the Feasible: A Practical Guide for Setting Up Patient Registries for the Collection of Real-World Data for Health Care Decision Making Based on Dutch Experiences.

OBJECTIVES: The aim of this article was to provide practical guidance in setting up patient registries to facilitate real-world data collection for health care decision making. METHODS: This guidance was based on our experiences and involvement in setting up patient registries in oncology in the Netherlands. All aspects were structured according to 1) mission and goals ("the Why"), 2) stakeholders and funding ("the Who"), 3) type and content ("the What"), and 4) identification and recruitment of patients, data handling, and pharmacovigilance ("the How"). RESULTS: The mission of most patient registries is improving patient health by improving the quality of patient care; monitoring and evaluating patient care is often the primary goal ("the Why"). It is important to align the objectives of the registry and agree on a clear and functional governance structure with all stakeholders ("the Who"). There is often a trade off between reliability, validity, and specificity of data elements and feasibility of data collection ("the What"). Patient privacy should be carefully protected, and address (inter-)national and local regulations. Patient registries can reveal unique safety information, but it can be challenging to comply with pharmacovigilance guidelines ("the How"). CONCLUSIONS: It is crucial to set up an efficient patient registry that serves its aims by collecting the right data of the right patient in the right way. It can be expected that patient registries will become the new standard alongside randomized controlled trials due to their unique value.

Dutch Melanoma Treatment Registry: Quality assurance in the care of patients with metastatic melanoma in the Netherlands.

BACKGROUND: In recent years, the treatment of metastatic melanoma has changed dramatically due to the development of immune checkpoint and mitogen-activated protein (MAP) kinase inhibitors. A population-based registry, the Dutch Melanoma Treatment Registry (DMTR), was set up in July 2013 to assure the safety and quality of melanoma care in the Netherlands. This article describes the design and objectives of the DMTR and presents some results of the first 2 years of registration. METHODS: The DMTR documents detailed information on all Dutch patients with unresectable stage IIIc or IV melanoma. This includes tumour and patient characteristics, treatment patterns, clinical outcomes, quality of life, healthcare utilisation, informal care and productivity losses. These data are used for clinical auditing, increasing the transparency of melanoma care, providing insights into real-world cost-effectiveness and creating a platform for research. RESULTS: Within 1 year, all melanoma centres were participating in the DMTR. The quality performance indicators demonstrated that the BRAF inhibitors and ipilimumab have been safely introduced in the Netherlands with toxicity rates that were consistent with the phase III trials conducted. The median overall survival of patients treated with systemic therapy was 10.1 months (95% confidence interval [CI] 9.1-11.1) in the first registration year and 12.7 months (95% CI 11.6-13.7) in the second year. CONCLUSION: The DMTR is the first comprehensive multipurpose nationwide registry and its collaboration with all stakeholders involved in melanoma care reflects an integrative view of cancer management. In future, the DMTR will provide insights into challenging questions regarding the definition of possible subsets of patients who benefit most from the new drugs.

A practical guide for using registry data to inform decisions about the cost effectiveness of new cancer drugs: lessons learned from the PHAROS registry.

Decision makers increasingly request evidence on the real-world cost effectiveness of a new treatment. There is, however, a lack of practical guidance on how to conduct an economic evaluation based on registry data and how this evidence can be used in actual decision making. This paper explains the required steps on how to perform a sound economic evaluation using examples from an economic evaluation conducted with real-world data from the Dutch Population based HAematological Registry for Observational Studies. There are three main issues related to using registry data: confounding by indication, missing data, and insufficient numbers of (comparable) patients. If encountered, it is crucial to accurately deal with these issues to maximize the internal validity and generalizability of the outcomes and their value to decision makers. Multivariate regression modeling, propensity score matching, and data synthesis are well-established methods to deal with confounding. Multiple imputation methods should be used in cases where data are missing at random. Furthermore, it is important to base the incremental cost-effectiveness ratio of a new treatment compared with its alternative on comparable groups of (matched) patients, even if matching results in a small analytical population. Unmatched real-world data provide insights into the costs and effects of a treatment in a real-world setting. Decision makers should realize that real-world evidence provides extremely valuable and relevant policy information, but needs to be assessed differently compared with evidence derived from a randomized clinical trial.

Experience with outcomes research into the real-world effectiveness of novel therapies in Dutch daily practice from the context of conditional reimbursement.

Policymakers more often request outcomes research for expensive therapies to help resolve uncertainty of their health benefits and budget impact at reimbursement. Given the limitations of observational data, we assessed its usefulness in evaluating clinical outcomes for bortezomib in advanced multiple myeloma patients. Data were retrospectively collected from patients included in the pivotal Assessment of Proteasome Inhibition for Extending Remissions trial (APEX; n=333) and two groups of daily practice patients treated with bortezomib following progression from upfront therapy (n=201): real-world patients treated as of May 2009 (RW-1; n=72) and June 2012 (RW-2; n=129). Prognosis, treatment, and effectiveness were compared. Outcomes research was useful for policymakers for addressing to whom and how bortezomib was administered in daily practice. It was limited however in generating robust evidence on real-world safety and effectiveness. The quality of real-world evidence on effectiveness was low due to missing data in patient charts, existing treatment variation and the dynamics in care during the novel drug's initial market uptake period. Policymakers requesting real-world evidence on clinical outcomes for reimbursement decisions should be aware of these limitations and advised to carefully consider beforehand the type of evidence that best addresses their needs for the re-assessment phase.

Policymaker, please consider your needs carefully: does outcomes research in relapsed or refractory multiple myeloma reduce policymaker uncertainty regarding value for money of bortezomib?

INTRODUCTION: Dutch policy regulations require outcomes research for the assessment of appropriate drug use and cost-effectiveness after 4 years of temporary reimbursement. We investigated whether outcomes research reduced policymaker uncertainty regarding the question whether the costs are worth public funding. METHODS: Our cohort study included 139 patients with relapsed/refractory multiple myeloma who were treated outside of a clinical study; 72 received bortezomib and 67 did not receive bortezomib. Detailed data were retrospectively collected from medical records in 38% of Dutch hospitals. RESULTS: All patients received second-line treatment; 65%, 40%, and 14%, received three, four, or five or more lines of therapy. Neither a specific treatment sequence nor an appropriate comparator could be identified because of large variation in regimes. Kaplan-Meier curves showed an increased overall survival (mean [median] 29.5 [33.2] vs. 28.0 [21.6] months) for patients treated with bortezomib (Wilcoxon P = 0.01). Total mean costs were €81,626 (range €17,793-€229,783) and €52,760 (range €748-€179,571) for patients receiving bortezomib and patients not receiving bortezomib, respectively. Patients treated with bortezomib, however, were not comparable to other patients despite attempts to correct for confounding. Therefore, it was impossible to develop a feasible model to obtain a valid incremental cost-effectiveness estimate. CONCLUSIONS: It was possible to develop evidence on bortezomib's use, effects, and costs in everyday practice. Much uncertainty, however, remained regarding its cost-effectiveness. Policymakers should carefully consider whether outcomes research sufficiently decreases uncertainty or whether other options (e.g., finance- and/or outcomes-based risk-sharing arrangements) are more appropriate to ensure sufficient value for money of expensive drugs.

Do reassessments reduce the uncertainty of decision making? Reviewing reimbursement reports and economic evaluations of three expensive drugs over time.

OBJECTIVE: To investigate the desirability and feasibility of a cyclic reimbursement process to address uncertainty accompanying initial decision making. METHODS: We performed desk research for three expensive outpatient drugs: imatinib, pegfilgrastim, and adalimumab. We analysed the evidence base at the time of decision making (T=0) and May 2011 (T=1). For T=0, public reports of the Dutch reimbursement agency were investigated regarding available clinical and economic evidence, and a systematic review was performed to retrieve additional economic evidence. For T=1, the systematic review was extended till May 2011. RESULTS: The evidence base at T=0 lacked information on clinically relevant outcomes such as mortality, morbidity, and quality of life (5/8 reports), (long-term) adverse events (2/8 reports) and experience in use (1/8 reports). One budget impact analysis and one economic evaluation were available but no pharmacoeconomic dossiers. The systematic review identified 39 cost-utility studies (of 52 economic evaluations) for T=1, characterised by methodological heterogeneity. CONCLUSIONS: Given the considerable uncertainty accompanying initial decision-making, a more cyclic reimbursement process seems feasible to reduce uncertainty regarding the therapeutical and economical value of expensive drugs. A mandatory evidence development requirement seems desirable to sufficiently meet decision makers' needs.

Practical feasibility of outcomes research in oncology: lessons learned in assessing drug use and cost-effectiveness in The Netherlands.

OBJECTIVE: To investigate the practical feasibility to develop evidence on drug use and cost-effectiveness in oncology practice. PATIENTS AND METHODS: Feasibility was examined using three Dutch case studies. Each case study investigated the degree of appropriate drug use and its incremental cost-effectiveness. Detailed data were retrospectively collected from hospital records. In total, 391, 316 and 139 patients with stage III colon cancer, metastatic colorectal cancer and multiple myeloma were included in 19, 29 and 42 hospitals, respectively. RESULTS: The methods used in the case studies were feasible to develop evidence on some aspects of drug use including types of treatments used, dosages, dose modifications and healthcare costs. Aspects such as baseline patient characteristics, reasons to start or stop a treatment and treatment effects were less feasible because of missing values. Despite difficulties to correct for confounding by indication, it was possible to estimate incremental cost-effectiveness by synthesising evidence in two of the three case studies. CONCLUSION: It is possible to generate evidence about drug use and cost-effectiveness in oncology practice to facilitate informed decision-making by both payers and physicians. This can improve quality of care and enhance the efficient allocation of resources. However, the optimal approach differs between drugs and their indications. Generating high-quality evidence requires active interdisciplinary collaboration. Patient registries can facilitate data collection but cannot resolve all issues. In most circumstances it is inevitable to use data-synthesis to obtain valid incremental cost-effectiveness estimates, but for some indications it will not be feasible to derive a valid and precise estimate.

[New drugs: money-back guarantee?]. / Nieuwe geneesmiddelen: niet goed, geld terug?

When a new medical technology, for example a new drug, is introduced onto the market there should be a discussion of the balance between "uncertainty versus value to society and demand". The new technology is sometimes given the benefit of the doubt due to a lack of information. Follow-up investigation is actually essential but is seldom mandatory and hardly ever spontaneously initiated. Specific measures, based on stimulation or penalization, could reduce the degree of uncertainty concerning the efficacy, safety and efficiency of a new technology. A serious option when a new drug produces disappointing results is to pay the manufacturer less.

The unit costs of inpatient hospital days, outpatient visits, and daycare treatments in the fields of oncology and hematology.

OBJECTIVES: Many economic evaluations are conducted in the fields of oncology and hematology, partially owing to the introduction of new expensive drugs in this field. Even though inpatient days, outpatient visits, and daycare treatments are frequently the main drivers of total treatment costs, their unit costs often lack generalizability. Therefore, we aimed to determine the unit costs of inpatient hospital days, outpatient visits, and daycare treatments specifically for oncological and hematological diseases in The Netherlands from the hospital's perspective. METHODS: Unit costs were collected from 30 oncological and hematological departments of 6 university and 24 general hospitals. Costs included direct labor and indirect labor, hotel and nutrition, overheads and capital. Ordinary least squares regression models were constructed to examine the degree of association between unit costs and hospital and hospital department characteristics. All costs were based on Euro 2007 cost data. RESULTS: At university hospitals, the unit costs per inpatient day were determined at €633 in oncological and €680 in hematological departments. At general hospitals, the mean costs per inpatient day were €400. Unit costs for inpatient hospital days, outpatient visits. and daycare treatments equalled the relative ratio 100:21:44. Direct labor costs were the major cost driver and the type of hospital (university, yes/no) was a strong predictor of unit costs. CONCLUSIONS: The present study provided unit costs for inpatient hospital days, outpatient visits, and daycare treatments in the fields of oncology and hematology. The results may be used as Dutch reference unit prices in economic evaluations assessing oncological and hematological diseases.