A blueprint for health technology assessment capacity building: lessons learned from Malta.

OBJECTIVES: The development and strengthening of health technology assessment (HTA) capacity on the individual and organizational level and the wider environment is relevant for cooperation on HTAs. Based on the Maltese case, we provide a blueprint for building HTA capacity. METHODS: A set of activities were developed based on Pichler et al.'s framework and the starting HTA capacity in Malta. Individual level activities focused on strengthening epidemiological and health economic skills through online and in-person training. On the organizational level, a new HTA framework was developed which was subsequently utilized in a shadow assessment. Awareness campaign activities raised awareness and support in the wider environment where HTAs are conducted and utilized. RESULTS: The time needed to build HTA capacity exceeded the planned two years accommodating the learning progress of the assessors. In addition to the planned trainings, webinars supplemented the online courses, allowing for more knowledge exchange. The advanced online course was extended over time to facilitate learning next to the assessors' daily tasks. Training sessions were added to implement the new economic evaluation framework, which was utilized in a second shadow assessment. Awareness by decision-makers was achieved with reports, posters, and an article on the current and developing HTA capacity. CONCLUSIONS: It takes time and much (hands-on) training to build skills for conducting complex assessment such as HTAs. Facilitating exchange with knowledgeable parties is crucial for succeeding as well as the buy-in of local managers motivating staff. Decision-makers need to be on-boarded for the continued success of HTA capacity building.

A SWOT analysis of the complex interdependencies of the Maltese reimbursement processes.

Background: The processes that operationalize the evaluation framework for new medicines are implemented to reach the system objectives of public health, financial sustainability, and equitability. However, when the activities and procedures of these processes are misaligned, the objectives of the system may be at risk. Objectives: To evaluate the supporting processes for introducing new medicines in public healthcare services in Malta. Methods: We first reviewed literature on the Maltese reimbursement system and subsequently conducted semi-structured interviews based on the Hutton Framework. Interviewees included policy makers, committee members, procurement staff, medical specialists, pharmacists, and pharmaceutical industry representatives. After validation, we analysed the data with a Strengths, Weaknesses, Opportunities, and Threats (SWOT) analysis. Results: Most medicines are assessed for introduction on the Government Formulary List. Exceptional requests fall outside this policy and pass through the Exceptional Medicinal Treatment route. Efficiency, quality, and transparency are major weaknesses across the supporting processes. Taking up responsibility, however, is considered the most important factor in reaching system objectives. Stakeholders tend to shift responsibilities to other processes, start/stop activities that impact the activities of subsequent processes whilst dismissing any contribution to the weaknesses of the system. Consequently, system objectives cannot be reached in an optimum manner. Conclusions: The Maltese case showed that recommendations for introducing new medicines in the public healthcare setting are influenced beyond the choice of HTA tools and criteria. Earmarked budgets, political steering, delays, and uninformed applicants as well as HTA capacity are impeding on system goals of public health, equity, and sustainability.

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.

Hospital-based or home-based administration of oncology drugs? A micro-costing study comparing healthcare and societal costs of hospital-based and home-based subcutaneous administration of trastuzumab.

OBJECTIVE: To investigate resource use and time investments of healthcare professionals, patients and their family and to compare healthcare and societal costs of one single hospital-based and one single home-based subcutaneous administration of trastuzumab in The Netherlands. METHOD: We conducted a bottom-up micro-costing study. Patients diagnosed with HER2+ early or metastatic breast cancer were recruited in four Dutch hospitals. For healthcare costs, data were collected on drug use, consumables, use of healthcare facilities, time of healthcare professionals, and travelling distance of the nurse. For societal costs, data were collected on patient and family costs (including travelling expenses and time of informal caregivers) and productivity losses of paid and unpaid work. RESULTS: Societal costs of one single administration of SC trastuzumab were €1753 within the home-based and €1724 within the hospital-based setting. Drug costs of trastuzumab were identical in both settings (€1651). Healthcare costs were higher for home-based administration (€91 versus €47) mainly because of more time of healthcare professionals (110 versus 38 minutes). Costs for patient and family were, however, lower for home-based administration due to travelling expenses (€7 versus €0) and time of informal caregivers (€14 versus €4). Costs for productivity losses were similar for both settings. CONCLUSIONS: Home-based subcutaneous administration of trastuzumab is more time consuming for healthcare professionals and therefore more costly than hospital-based administration. The total budget impact can be large considering that a large number of patients receive a large number of cycles of oncology treatments. If home-based administration is the way forward, novel approaches are crucial for ensuring efficiency of home-based care.

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.

Health Economics as Rhetoric: The Limited Impact of Health Economics on Funding Decisions in Four European Countries.

BACKGROUND: A response to the challenge of high-cost treatments in health care has been economic evaluation. Cost-effectiveness analysis presented as cost per quality-adjusted life-years gained has been controversial, raising heated support and opposition. OBJECTIVES: To assess the impact of economic evaluation in decisions on what to fund in four European countries and discuss the implications of our findings. METHODS: We used a protocol to review the key features of the application of economic evaluation in reimbursement decision making in England, Germany, the Netherlands, and Sweden, reporting country-specific highlights. RESULTS: Although the institutions and processes vary by country, health economic evaluation has had limited impact on restricting access of controversial high-cost drugs. Even in those countries that have gone the furthest, ways have been found to avoid refusing to fund high-cost drugs for particular diseases including cancer, multiple sclerosis, and orphan diseases. Economic evaluation may, however, have helped some countries to negotiate price reductions for some drugs. It has also extended to the discussion of clinical effectiveness to include cost. CONCLUSIONS: The differences in approaches but similarities in outcomes suggest that health economic evaluation be viewed largely as rhetoric (in D.N. McCloskey's terms in The Rhetoric of Economics, 1985). This is not to imply that economics had no impact: rather that it usually contributed to the discourse in ways that differed by country. The reasons for this no doubt vary by perspective, from political science to ethics. Economic evaluation may have less to do with rationing or denial of medical treatments than to do with expanding the discourse used to discuss such issues.

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.

A comparative study of the role of disease severity in drug reimbursement decision making in four European countries.

Considerations beyond cost-effectiveness are important in reimbursement decision making. We assessed the importance of disease severity in drug reimbursement decision making in Belgium, France, The Netherlands and Sweden. We investigated scientific literature and policy documents and conducted three interviews in each country (four in The Netherlands) with persons involved in drug reimbursement. Disease severity is an important consideration, especially where the level is high. The Netherlands operationalizes disease severity using the proportional shortfall approach. Sweden uses categories to give an indication of the level of severity. In The Netherlands and Sweden, severity only implicitly plays a role in the decision whether to reimburse a drug, whereas in Belgium and France it also explicitly plays a role in determining the willingness to use public resources. Interviewees acknowledged that as well as a qualitative description of the disease, quantitative information may also be useful as input for decision making. None of them, however, considered this to be of decisive importance. Although disease severity is important in drug reimbursement decision making in all four countries, all seem to struggle in explicitly specifying its actual role. Belgium and France are the most explicit by using levels of severity in setting reimbursement levels; all four countries could, however, improve the transparency of its actual importance relative to the other criteria in the decision-making process.

Health economic evaluations in reimbursement decision making in the Netherlands: time to take it seriously?

Health technology assessment already informed Dutch policymaking in the early 1980s. Evidence of health economic evaluations is, however, only systematically used in drug reimbursement decision making. Outpatient drugs with an added therapeutic value and expensive specialist drugs require evidence from an economic evaluation. Due to many exemptions, however, the availability of evidence of health economic evaluations remains rather low. Although the Dutch reimbursement agency suggested a cost-effectiveness threshold range depending on the severity of the disease (i.e., €10,000 - 80,000 per Quality Adjusted Life Year), it was never confirmed nor endorsed by the Ministry of Health. It is highly questionable whether health economic evaluations currently play a role in actual Dutch reimbursement decision making. Although the requirements exist in policy procedures, recent cases show that Dutch policymakers experience great difficulties in putting restrictions on reimbursement based on evidence from health economic evaluations. The near future will show whether the need will increase to base decisions on societal value for money, and whether Dutch policymakers show the courage to take health economic evaluations seriously.

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.

Unravelling drug reimbursement outcomes: a comparative study of the role of pharmacoeconomic evidence in Dutch and Swedish reimbursement decision making.

BACKGROUND: To sustainably manage equitable access to effective drugs, many developed countries have established a national system to determine whether drugs should be reimbursed. OBJECTIVES: Our objectives were (i) to investigate the role of pharmacoeconomic evidence in Dutch and Swedish drug reimbursement decision making; and (ii) to determine the extent to which appraising the importance of full economic evaluations relative to other evidence is a transparent process. DATA SOURCES: Data sources included all Dutch and Swedish drug reimbursement information published in the period January 2005 to July 2011. METHODS: After categorising all the reimbursement applications and decisions in published data sources, we selected all dossiers-in both countries-that included a full economic evaluation (i.e. cost-effectiveness and/or cost-utility analysis) and then investigated how the evidence was appraised for its societal value. RESULTS: In The Netherlands, only 35 % of the 118 applications on List 1B (i.e. claiming added therapeutic value) were found to include pharmacoeconomic evidence. In all cases where drugs received a 'no' decision, combined with an evaluation that they were of similar (n = 7) or added (n = 5) therapeutic value, we found that the pharmacoeconomic evidence had been judged insufficiently robust. We also found that in 21 % of the 'yes' decisions, combined with an evaluation of similar (n = 2) or added (n = 2) therapeutic value, the pharmacoeconomic evidence had been judged insufficiently robust. In Sweden, we found that drugs that received a 'no' decision (n = 39) had been judged either not cost effective (74 %) or not supported by sufficiently credible data (26 %). Nearly all drugs that received a 'yes' decision (n = 252) had been judged cost effective (92 %). However, of all these judgements, 53 % were based on a price comparison and 10 % on a cost-minimisation analysis; only 33 % were based on a full economic evaluation. More economic evaluations were available in Sweden than in The Netherlands (97 vs. 31, respectively), mainly due to the numerous exemptions from pharmacoeconomic evidence in The Netherlands (65 %). Dossiers for only 11 drugs included a full economic evaluation in both countries; of these, the reimbursement decisions differed for four drugs. Appraisal elements were reported only descriptively; their actual influence on the final decision remained unclear. In four dossiers, the (high) severity of the treatable disease was explicitly mentioned in both countries; three of these were identical and related to indications in cancer. CONCLUSIONS: Both countries publish drug reimbursement information. Therapeutic value appears to be the most decisive criterion; the relative importance of full economic evaluations is more modest than would generally be expected, especially in The Netherlands. Although the assessment process is reasonably transparent, both countries could make the appraisal process more transparent by more explicitly showing the actual role of each different (societal) criterion in their decision making.

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.

Health system goals: a discrete choice experiment to obtain societal valuations.

OBJECTIVE: To improve previous approaches to health system goals valuation. METHODS: We reviewed literature on health system performance and previous comparative performance assessments, and combined this with literature on process utility to create a theoretical foundation for health system goals. We used a discrete choice experiment to elicit goal weights. To obtain social justice weights respondents were placed behind a 'veil of ignorance'. To ensure that respondents understood their task, we instructed them in a classroom setting. RESULTS: We identified five health system goals. All five goals significantly affected choice behavior. An equitable distribution of health obtained the highest weight (0.34), followed by average level of health (0.29) and financial fairness (0.24). Both process outcomes (utility derived from the process and its distribution) received much lower weights (0.07 and 0.06, respectively). CONCLUSIONS: Our framework adds to that of the World Health Organization. We demonstrated the feasibility of measuring societal valuation of health system goals with a multi-attribute technique based on trade-offs. Our weights placed much greater emphasis on health and health inequality than on process outcomes. Our study improves the methodology of international health system performance comparison and thereby enhances global evidence-based health policy information.