Cost Effectiveness of Endovascular Ultrasound Renal Denervation in Patients with Resistant Hypertension.

BACKGROUND: Resistant hypertension (rHTN) is defined as blood pressure (BP) of ≥ 140/90 mmHg despite treatment with at least three antihypertensive medications, including a diuretic. Endovascular ultrasound renal denervation (uRDN) aims to control BP alongside conventional BP treatment with antihypertensive medication. This analysis assesses the cost effectiveness of the addition of the Paradise uRDN System compared with standard of care alone in patients with rHTN from the perspective of the United Kingdom (UK) health care system. METHODS: Using RADIANCE-HTN TRIO trial data, we developed a state-transition model. Baseline risk was calculated using Framingham and Prospective Cardiovascular Münster (PROCAM) risk equations to estimate the long-term cardiovascular risks in patients treated with the Paradise uRDN System, based on the observed systolic BP (SBP) reduction following uRDN. Relative risks sourced from a meta-analysis of randomised controlled trials were then used to project cardiovascular events in patients with baseline SBP ('control' patients); utility and mortality inputs and costs were derived from UK data. Costs and outcomes were discounted at 3.5% per annum. Modelled outcomes were validated against trial meta-analyses and the QRISK3 algorithm and real-world evidence of RDN effectiveness. One-way and probabilistic sensitivity analyses were conducted to assess the uncertainty surrounding the model inputs and sensitivity of the model results to changes in parameter inputs. Results were reported as incremental cost-effectiveness ratios (ICERs). RESULTS: A mean reduction in office SBP of 8.5 mmHg with uRDN resulted in an average improvement in both absolute life-years (LYs) and quality-adjusted life-years (QALYs) gained compared with standard of care alone (0.73 LYs and 0.67 QALYs). The overall base-case ICER with uRDN was estimated at £5600 (€6500) per QALY gained (95% confidence interval £5463-£5739 [€6341-€6661]); modelling demonstrated > 99% probability that the ICER is below the £20,000-£30,000 (€23,214-€34,821) per QALYs gained willingness-to-pay threshold in the UK. Results were consistent across sensitivity analyses and validation checks. CONCLUSIONS: Endovascular ultrasound RDN with the Paradise system offers patients with rHTN, clinicians, and healthcare systems a cost-effective treatment option alongside antihypertensive medication.

Data Governance for Real-World Data Management: A Proposal for a Checklist to Support Decision Making.

OBJECTIVES: Real-world data (RWD) and real-world evidence (RWE) can provide extensive information on healthcare for use in health technology assessment and decision making. Nevertheless, there is a lack of consensus surrounding the appropriate data governance (DG) practices for RWD/RWE. Data sharing is also a large concern, especially considering evolving data protection regulations. Our objective is to propose recommendations for international standards of evaluating the acceptability of RWD governance practices. METHODS: After reviewing the literature, we created a checklist targeting DG practices for RWD/RWE. We then carried out a 3-round Delphi panel, including European policy makers, health technology assessment experts, and hospital managers. The consensus for each statement was measured and the checklist adjusted accordingly. RESULTS: The literature review identified the main topics regarding RWD/RWE DG practices: data privacy and security, data management and linkage, data access management, and the generation and use of RWE. Members of the Delphi panel (21 experts/25 invited) were presented a total of 24 statements related to each of the topics. Experts demonstrated a progressive level of consensus and importance ratings in all topics and to most statements. We suggest a refined checklist in which the statements rated less important or with less consensus have been removed. CONCLUSIONS: This study suggests how the DG of RWD/RWE could be qualitatively evaluated. We propose checklists that could be used by all RWD/RWE users to help ensure the quality and integrity of RWD/RWE governance and complement data protection law.

The Real-World Evidence Workstream in EUreccA 2025: How the Task Was Addressed.

This is one of a series of articles that consider the barriers to optimal use of real-world evidence (RWE) in health technology assessment (HTA) as well as ways to overcome them. The work was carried out as part of EUreccA 2025 (European Initiative for New Reimbursement and Access Approaches 2025), in particular with the RWE workstream embodied within that collaboration. The starting premises of this workstream were as follows: (1) the acceptance of RWE by HTA agencies and payers in the assessment of drugs is suboptimal and variable between jurisdictions, and (2) if that were not the case, the path of new pharmaceuticals to patients could be quicker and less expensive. Elsewhere in this issue we set out the conclusions we had reached in the EUreccA RWE workstream. In this article, we set out the methodology used to conduct the totality of the EureccA 2025 RWE workstream effort, which led us to those conclusions. The main results, strengths, and limitations of the individual parts are discussed further in separate articles in this supplement. Through scoping work, we generated 4 key topics within which to identify and address the barriers to optimal RWE use in HTA. Through pragmatic literature searches, stakeholder engagement, and case studies, we suggest ways in which the problems identified may be addressed as a contribution to progress in this area.

Across-Country Variations of Real-World Data and Evidence for Drugs: A 5-European-Country Study.

OBJECTIVES: This study aimed to describe the role of real-world data (RWD) and real-world evidence (RWE) in health technology assessment (HTA) in 5 European countries and to identify the hurdles to the acceptance of RWE and suggest directions toward its more effective use. METHODS: Authors from France, Germany, Italy, and Sweden used a common template to extract evidence. For England, the Cancer Drugs Fund was described and analyzed as a particular model for the use of RWD to provide evidence for coverage decisions and managed entry agreements. RESULTS: In all countries except Germany, HTA bodies acknowledged the relevance of RWD/RWE to address postlaunch uncertainties. In Germany, evidence from randomized controlled trials remains the gold standard, and evidence based on RWD is generally rejected. Multiple sources of RWD exist, but the quality, the immediate relevance of existing sources, and their interoperability limit their adaptation to the specifics of a given drug. This leads to skepticism about the validity of the evidence. Timing is also a key issue: the production of evidence may not be synchronized with the HTA and pricing bodies' agendas. The Cancer Drugs Fund case emphasizes that a strong partnership among all stakeholders and a pragmatic use of existing data, alongside clinical evidence provided by companies, are key success factors. CONCLUSIONS: A continuous investment in national health information systems is a key issue for providing valid RWE. Processes and aids to guide the acceptability and usage of RWE derived from pairing between sources and questions are essential.

Using Real-World Data in the Health Technology Assessment of Pharmaceuticals: Strengths, Difficulties, and a Pragmatic Way Forward.

In the past decade, there have been increasing calls for greater use of real-world evidence (RWE) and data (RWD), with the explicit goal of enabling faster provision of effective medicines to patients in need. The push for decision makers to accept RWE is especially noticeable in the pursuit of regulatory approval, but RWE, particularly when used to estimate the relative effectiveness of interventions, is not always readily accepted by agencies responsible for reimbursement and pricing of new pharmaceuticals and, to a varying degree, is not accepted across jurisdictions. This lack of trust hampers the use of RWE despite a very large and growing literature base on the principles of how RWE should be used. In this article, we suggest an important part of the explanation of why this situation has arisen and make suggestions for its alleviation. Given that problems commonly arise that are particular to the question being asked and the data sources being used, general guidance on the principles of how to use RWD cannot cover all eventualities. Therefore, we are suggesting the creation of an archive, or repository, to record uses of RWD in support of decisions by funding bodies or their advisors. This article introduces a proposed, structured classification of decision types using RWE, around which evidence can be assembled in a curated source (RWD/RWE taxonomy) and thus facilitate judgments on when evidence is "good enough." This article is part of a series in a special issue of this journal that looks at the barriers to optimal use of RWE in health technology assessment and how to overcome them. We begin significantly to populate our "taxonomy" with examples in an accompanying article. We also propose recommendations for international standards of evaluating the acceptability of RWD governance practices.

Structure and Content of a Taxonomy to Support the Use of Real-World Evidence by Health Technology Assessment Practitioners and Healthcare Decision Makers.

This is one of a series of articles that consider the barriers to optimal use of real-world evidence (RWE) in health technology assessment and how to overcome them. The work was performed as part of EUreccA 2025, in particular with the RWE workstream embodied within that collaboration. Elsewhere in this issue we described the reasoning and process that led us to develop practical tools to support RWE use, including this taxonomy and explained the methods used to do so. The taxonomy classifies questions that are typically addressed using real-world data in health technology assessment and the data sources typically used to address these questions. In this article, we describe the taxonomy itself. For as many of the pairings as possible, we have provided links to advice and methods on how to address the associated question using those data. We have also provided links to examples of RWE use in practical decision making to answer the questions posed. Our work is not complete, but we believe it is sufficient to demonstrate the value of such a taxonomy and information source if it is completed and curated as a "wiki" by the community that would use it.

Cost-effectiveness of a paclitaxel-eluting stent (Eluvia) compared to Zilver PTX for endovascular femoropopliteal intervention.

OBJECTIVES: Antiproliferative therapies based on paclitaxel have been developed to extend the durability of endovascular interventions for lower-extremity atherosclerotic peripheral artery disease, resulting in improved primary vessel patency and fewer target lesion revascularizations. This study evaluated the cost-effectiveness of the sustained-release, paclitaxel-eluting Eluvia stent (Boston Scientific, Marlborough, MA) versus the paclitaxel-coated Zilver PTX stent (Cook Medical, Bloomington, IN) for endovascular intervention in the superficial femoral or proximal popliteal artery. DESIGN: A microsimulation model was constructed from a United States Medicare perspective with a 24-month time horizon. Patients entering the model were assigned to initial endovascular intervention with either Eluvia or Zilver PTX. Each month patients were exposed to the risks of primary vessel patency loss, target lesion revascularization, amputation, and death. Clinical input parameters were taken from a randomized trial (IMPERIAL) comparing the two interventions at 24-months follow-up. Cost parameters were obtained from analyses of Medicare administrative and claims data. Cost-effectiveness analysis entailed sampling a complete set of clinical and cost parameters from their respective distributions, and then running cohorts of 10,000 patients through each intervention arm of the model. One-way and probabilistic sensitivity analyses were performed. RESULTS: In the base case microsimulation, at 24 months, the modeled target lesion revascularization was 11.6% for Eluvia and 19.0% for Zilver PTX, and the mean total direct costs were $20,010 and $21,356, respectively (Eluvia average savings=$1,346). In probabilistic sensitivity analyses, Eluvia was cost-effective in 87.8% of all simulations at a willingness-to-pay threshold of $10,000 per target lesion revascularization prevented. Eluvia was more effective and less costly (dominant) than Zilver PTX in 73.6% of simulations. CONCLUSIONS: In this comparison of a paclitaxel-eluting to a paclitaxel-coated stent for endovascular femoropopliteal intervention, Eluvia was more effective and less costly (dominant) than Zilver PTX from a US Medicare perspective. These findings should be considered when formulating reimbursement policy and clinical practice guidelines.

Paclitaxel is a drug used in the treatment of peripheral artery disease (PAD) to help maintain primary vessel patency and reduce the need for revascularization procedures. This study evaluated the cost-effectiveness of the paclitaxel-eluting Eluvia stent (Boston Scientific, Marlborough, MA) versus the paclitaxel-coated Zilver PTX stent (Cook Medical, Bloomington, IN) in Medicare patients with PAD. Cost-effectiveness is defined as the degree to which a particular treatment option is effective relative to its costs. Therefore, this study compared both the effectiveness, in terms of target lesion revascularization rates, and the costs of Eluvia versus Zilver PTX over 24 months.A microsimulation model was developed from a United States Medicare perspective with a 24-month time horizon. Simulated patients entered the model and were assigned to receive either Eluvia or Zilver PTX. Monthly, patients were exposed to the risks of primary vessel patency loss, target lesion revascularization (TLR), amputation, and death. These risks were taken from a randomized controlled trial that compared Eluvia and Zilver PTX over 24 months. Patients also accrued costs over time. The costs used in the model were obtained from Medicare administrative and claims data analyses.In health economics, a treatment is considered to be the dominant treatment option if it is both more effective and less costly than the alternative treatment. In this case, Eluvia was found to be dominant over Zilver PTX because it was associated with lower TLR rates and lower costs. These findings should be considered when formulating reimbursement policy and clinical practice guidelines.

Varying Willingness to Pay Based on Severity of Illness: Impact on Health Technology Assessment Outcomes of Inpatient and Outpatient Drug Therapies in The Netherlands.

OBJECTIVES: Since 2015, Zorginstituut Nederland (ZIN) has linked disease severity ranges of 0.10 to 0.40, 0.41 to 0.70, and 0.71 to 1.00 with willingness-to-pay (WTP) reference values of €20 000, €50 000, and €80 000 per quality-adjusted life year gained, respectively. We sought to review whether these changes have affected ZIN health technology assessment (HTA) outcomes for specialist and outpatient drugs. METHODS: ZIN recommendations for specialist and outpatient drugs published between January 1, 2012, and December 31, 2020, that included a pharmacoeconomic report were reviewed. Data were extracted on disease severity, proportional shortfall calculation, reported WTP reference value, outcomes related to the cost-effectiveness of the product, budget impact, and ZIN's recommendation including rationale for their advice. RESULTS: A total of 51 HTAs were included. Of the 20 HTAs published before June 2015, a total of 9 received positive recommendations, 7 were conditionally reimbursed, and 4 received negative recommendations. None reported WTP reference values. Of the 31 evaluations published after June 2015, a total of 4 products received positive recommendations, 1 was conditionally approved, and 26 received negative recommendations initially. Most products (65%) reported disease severity to be >0.70. CONCLUSIONS: Since 2015, most products have fallen within the highest category of disease severity. Although pre-2015 outcomes were varied, post-2015 products overwhelmingly received negative recommendations, and the proportion of products for which price negotiations were recommended has increased. These differences in outcomes may result from the introduction of an explicit WTP reference value, whether or not in combination with the severity-adjusted ranges, but may also reflect other national policy changes in 2015.

HTA and economics in the United States: a systematic review of ICER reports to evaluate trends, identify factors associated with recommendations, and understand implications.

BACKGROUND: The Institute for Clinical and Economic Review (ICER) is a prominent health technology assessment (HTA) entity in the United States that considers costs and applies economic analyses to derive price-based recommendations. ICER continues to adjust its value framework, yet discussion persists regarding whether ICER methodologies align with established research standards. This work evaluates ICER assessments relative to those standards, providing a benchmark with the release of ICER's most recent value framework update. OBJECTIVES: To evaluate ICER economic assessments for trends, factors related to recommendations, and quality for use in U.S. decision making. METHODS: We evaluated all ICER final evidence reports published between 2006 and August 31, 2019, with regard to base-case result trends over time, pricing sources, comparator selection, analytic perspectives, model uncertainty, how modeling results aligned with ICER's determinations of value for money, and comparison of ICER methodological approaches with established modeling standards. Analyses were stratified by time period, where appropriate, to account for changes in ICER's framework over time. RESULTS: Of 58 ICER final evidence reports, 47 used the most commonly reported outcome (cost per quality-adjusted life-year [QALY]); ICER-developed models evaluated 131 interventions and comparators with 238 base-case results. Pricing sources for ICER reports became more standardized in 2017, although sources were not associated with the likelihood of falling below ICER's cost-effectiveness thresholds. In 30% of base-case analyses (n = 72), ICER did not use a clinical comparator, although reasonable treatments were available. In modified societal perspectives scenarios applied in later assessments, 75% of analyses (n = 76) included productivity but did not specify how it was quantified. Reports did not explain how sensitivity and scenario analyses were selected or implications of results. ICER value for money determinations generally aligned with cost-effectiveness results, although 2 of 33 (6%) interventions ranked as low value and 3 of 5 (60%) interventions ranked as low-moderate value, met a $150,000 per QALY threshold, and 14 of 37 (38%) moderate-value interventions exceeded this threshold; the most common rationale was related to national budget impact. CONCLUSIONS: While some progress has been made, further improvement is needed to ensure that ICER assessments address the most relevant questions for target audiences, adhere to established research standards, and are reported in a manner that can be readily interpreted and applied to policymaking. DISCLOSURES: No outside funding supported this study. The authors have nothing to disclose.

Updated cost-effectiveness analysis of onabotulinumtoxinA for the prevention of headache in adults with chronic migraine who have previously received three or more preventive treatments in the UK.

Aims: OnabotulinumtoxinA is recommended by NICE for the treatment of chronic migraine. This economic evaluation provides updated estimates of the cost-effectiveness of onabotulinumtoxinA for chronic migraine using new utility estimates in an existing model structure.Methods: A previously published model was revised to include EQ-5D utility estimates from a large observational study (REPOSE; n = 633). Efficacy data were taken from the pooled phase III PREEMPT clinical trial program, while resource utilization estimates were obtained from the International Burden of Migraine Study (IBMS). The model estimated costs and quality-adjusted life years (QALYs) gained over 2 years from the UK NHS perspective.Results: OnabotulinumtoxinA treatment resulted in total discounted incremental costs of £1,204 and an incremental discounted QALY gain of 0.07 compared with placebo in patients with chronic migraine who have previously failed three or more preventive treatments, corresponding to an incremental cost-effectiveness ratio (ICER) of £16,306 per QALY gained. Scenario analysis showed that the administration of onabotulinumtoxinA by a specialist nurse rather than a neurology consultant reduced the ICER from £16,306 to £13,832 per QALY gained. Removal of the positive stopping rule recommended in current NICE guidance increased the ICER to £20,768 per QALY for onabotulinumtoxinA vs. placebo. Combining these two scenarios produced an ICER of £17,686 per QALY gained.Conclusion: NICE recommended onabotulinumtoxinA for the prevention of chronic migraine in 2012 amid concerns about the uncertainty of ICER estimates, with a positive stopping rule used to manage some of these uncertainties. Since the publication of the NICE guidance, the REPOSE study provides a more recent source of utility data based on real-world evidence. The results of analyses including these utilities suggest that the application of the positive stopping rule may not be necessary to ensure cost-effectiveness and that this aspect of the current NICE guidance for onabotulinumtoxinA may merit reconsideration.

Challenging current views on bile acid diarrhoea and malabsorption.

BACKGROUND: In 2012, the National Institute for Health and Care Excellence (NICE) assessed guidance (DG7) on the use of tauroselcholic (75selenium) acid (also known as SeHCAT) for the investigation of diarrhoea due to bile acid malabsorption (BAM) in patients with IBS-D and in patients with Crohn's disease who have not had an ileal resection. NICE concluded that tauroselcholic (75selenium) acid was recommended for use in research only. NICE will be reviewing the decision to update the guidance for tauroselcholic (75selenium) acid, for these populations, in March 2017. AIM: Our aim is to summarise advances in BAM, also known as bile acid diarrhoea (BAD), and encourage clinicians to re-evaluate their understanding of this disorder. APPROACH: We review the prevalence, diagnosis and treatment of BAD/BAM. We describe the new evidence available since the original NICE review in 2012, and discuss the economic issues associated with failure to diagnose or to treat BAD/BAM accurately. EVIDENCE UPDATE: There is new and compelling evidence available since DG7, which shows that tauroselcholic (75selenium) acid scanning is a powerful tool in the diagnosis of BAD/BAM. We summarise published prevalence data (approximately 1% prevalence in the UK, as suggested by clinical practice diagnosis rates), and highlight that the true prevalence of BAD/BAM could be far greater than this. CONCLUSION: We present evidence that challenges current opinion about this disorder, and we commend both clinicians and health technology assessment (HTA) agencies for being open to arguments and new evidence in any future HTAs.

A Decision-Analytic Model to Assess the Cost-Effectiveness of Etelcalcetide vs. Cinacalcet.

INTRODUCTION: Etelcalcetide is a novel intravenous calcimimetic for the treatment of secondary hyperparathyroidism (SHPT) in haemodialysis patients. The clinical efficacy and safety of etelcalcetide (in addition to phosphate binders and vitamin D and/or analogues [PB/VD]) was evaluated in three phase III studies, including two placebo-controlled trials and a head-to-head study versus the oral calcimimetic cinacalcet. OBJECTIVE: The objective of this study was to develop a decision-analytic model for economic evaluation of etelcalcetide compared with cinacalcet. METHODS: We developed a life-time Markov model including potential treatment effects on mortality, cardiovascular events, fractures, and subjects' persistence. Long-term efficacy of etelcalcetide was extrapolated from the reduction in parathyroid hormone (PTH) in the phase III trials and the available data from the outcomes study in cinacalcet (EVOLVE trial). Etelcalcetide was compared with cinacalcet, both in addition to PB/VD. We applied unit costs averaged from five European countries and a range of potential etelcalcetide pricing options assuming parity price to weekly use of cinacalcet and varying it by a 15 or 30% increase. RESULTS: Compared with cinacalcet, the incremental cost-effectiveness ratio of etelcalcetide was €1,355 per QALY, €24,521 per QALY, and €47,687 per QALY for the three prices explored. The results were robust across the probabilistic and deterministic sensitivity analyses. CONCLUSIONS: Our modelling approach enabled cost-utility assessment of the novel therapy for SHPT based on the observed and extrapolated data. This model can be used for local adaptations in the context of reimbursement assessment.

Quality-adjusted life year difference in patients with predominant negative symptoms of schizophrenia treated with cariprazine and risperidone.

AIM: Our study aimed at estimating differences in quality-adjusted life year (QALY) gain for patients with predominant negative symptoms of schizophrenia treated with cariprazine compared with risperidone. MATERIALS & METHODS: A Markov model was built, based on the Mohr-Lenert approach and data derived from clinical trials, to estimate potential QALY gains of patients. RESULTS: Patients had higher probability of reaching better health states treated with cariprazine compared with risperidone. In the model, this resulted in an estimated QALY gain of 0.029 per patient, after 1 year of treatment. CONCLUSION: Cariprazine, which showed clinically meaningful improvement in the symptoms, and personal and social performance, can also provide significant QALY gain in the treatment of patients with predominant negative symptoms of schizophrenia compared with risperidone.

A systematic review of cost-effectiveness modeling of pharmaceutical therapies in neuropathic pain: variation in practice, key challenges, and recommendations for the future.

OBJECTIVES: Complexities in the neuropathic-pain care pathway make the condition difficult to manage and difficult to capture in cost-effectiveness models. The aim of this study is to understand, through a systematic review of previous cost-effectiveness studies, some of the key strengths and limitations in data and modeling practices in neuropathic pain. Thus, the aim is to guide future research and practice to improve resource allocation decisions and encourage continued investment to find novel and effective treatments for patients with neuropathic pain. METHODS: The search strategy was designed to identify peer-reviewed cost-effectiveness evaluations of non-surgical, pharmaceutical therapies for neuropathic pain published since January 2000, accessing five key databases. All identified publications were reviewed and screened according to pre-defined eligibility criteria. Data extraction was designed to reflect key data challenges and approaches to modeling in neuropathic pain and based on published guidelines. RESULTS: The search strategy identified 20 cost-effectiveness analyses meeting the inclusion criteria, of which 14 had original model structures. Cost-effectiveness modeling in neuropathic pain is established and increasing across multiple jurisdictions; however, amongst these studies, there is substantial variation in modeling approach, and there are common limitations. Capturing the effect of treatments upon health outcomes, particularly health-related quality-of-life, is challenging, and the health effects of multiple lines of ineffective treatment, common for patients with neuropathic pain, have not been consistently or robustly modeled. CONCLUSIONS: To improve future economic modeling in neuropathic pain, further research is suggested into the effect of multiple lines of treatment and treatment failure upon patient outcomes and subsequent treatment effectiveness; the impact of treatment-emergent adverse events upon patient outcomes; and consistent and appropriate pain measures to inform models. The authors further encourage transparent reporting of inputs used to inform cost-effectiveness models, with robust, comprehensive and clear uncertainty analysis and, where feasible, open-source modeling is encouraged.

Tramadol and the risk of fracture in an elderly female population: a cost utility assessment with comparison to transdermal buprenorphine.

INTRODUCTION: Opioid treatment for chronic pain is a known risk factor for falls and/or fractures in elderly patients. The latter cause a significant cost to the National Health Service and the Personal Social Services in the UK. Tramadol has a higher risk of fractures than some other opioid analgesics used to treat moderate-to-severe pain and, in the model described here, we investigate the cost effectiveness of transdermal buprenorphine treatment compared with tramadol in a high-risk population. METHODS: A model was developed to assess the cost effectiveness of tramadol compared with transdermal buprenorphine over a 1-year time horizon and a patient population of high-risk patients (female patients age 75 or older). To estimate the total cost and quality-adjusted life years (QALYs) of treatment, published odds ratios are used in combination with the published incidence rates of four types of fracture: hip, wrist, humerus and other. RESULTS: The model shows tramadol to be associated with 1,058 more fractures per 100,000 patients per year compared with transdermal buprenorphine, resulting in transdermal buprenorphine being cost-effective with an incremental cost-effectiveness ratio of less than £7,000 compared with tramadol. Sensitivity analysis found this result to be robust. LIMITATIONS: In the UK data, there is uncertainty regarding the transdermal buprenorphine odds ratios for fractures. Odds ratios published in Danish and Swedish studies show similar point estimates but are associated with less uncertainty. CONCLUSION: Transdermal buprenorphine is cost-effective compared to tramadol at a willingness-to-pay threshold of £20,000 per QALY.

The Suitability of End Point Designs for Health Technology Assessment in Chronic Pain Studies.

OBJECTIVES: To identify the pain instruments and study end points most commonly used in clinical trial settings and to provide insight into the extent to which outcome measures in clinical studies are meeting payer needs. METHODS: A literature review was conducted to identify published clinical studies and ongoing/recently completed registered trials in chronic pain. Inclusion criteria were interventional study, chronic pain in adults, and pain measured within the primary end point. RESULTS: Of 1256 PubMed citations and 3006 clinical trial registry entries, 356 reported large clinical studies in pain populations (e.g., malignant, neuropathic, functional, and musculoskeletal). Studies were designed for superiority in 28% of PubMed citations and 8% of registry entries. The primary end points of most studies were single-dimension pain instruments, such as the numerical rating scale (n = 131) and the visual analogue scale (n = 69). In cases in which multidimensional pain end points were used, this was most commonly the Brief Pain Inventory (n = 37). Payer-relevant end points were typically limited to secondary end points, and were limited and/or reported inconsistently in published studies and ongoing/recently completed studies: preference-weighted quality of life (36% and 42%), resource use (2% and 8%), physical function (28% and 39%), and psychological function (25% and 24%). CONCLUSIONS: Most pain trials were not designed to show superiority to an active comparator, and they used single-dimension pain scales as their primary end point in combination with a broader selection of secondary end points. The inclusion of payer-relevant end points among clinical trials was inconsistent.

The Budget Impact of Biosimilar Infliximab (Remsima®) for the Treatment of Autoimmune Diseases in Five European Countries.

INTRODUCTION: Inflammatory autoimmune diseases (rheumatoid arthritis, ankylosing spondylitis, Crohn's disease, ulcerative colitis, psoriasis, and psoriatic arthritis) have a considerable impact on patients' quality of life and healthcare budgets. Biosimilar infliximab (Remsima(®)) has been authorized by the European Medicines Agency for the management of inflammatory autoimmune diseases based on a data package demonstrating efficacy, safety, and quality comparable to the reference infliximab product (Remicade(®)). This analysis aims to estimate the 1-year budget impact of the introduction of Remsima in five European countries. METHODS: A budget impact model for the introduction of Remsima in Germany, the UK, Italy, the Netherlands, and Belgium was developed over a 1-year time horizon. Infliximab-naïve and switch patient groups were considered. Only direct drug costs were included. The model used the drug-acquisition cost of Remicade. The list price of Remsima was not known at the time of the analysis, and was assumed to be 10-30% less than that of Remicade. Key variables were tested in the sensitivity analysis. RESULTS: The annual cost savings resulting from the introduction of Remsima were projected to range from €2.89 million (Belgium, 10% discount) to €33.80 million (Germany, 30% discount). If any such savings made were used to treat additional patients with Remsima, 250 (Belgium, 10% discount) to 2602 (Germany, 30% discount) additional patients could be treated. The cumulative cost savings across the five included countries and the six licensed disease areas were projected to range from €25.79 million (10% discount) to €77.37 million (30% discount). Sensitivity analyses showed the number of patients treated with infliximab to be directly correlated with projected cost savings, with disease prevalence and patient weight having a smaller impact, and incidence the least impact. CONCLUSION: The introduction of Remsima could lead to considerable drug cost-related savings across the six licensed disease areas in the five European countries. FUNDING: Mundipharma International Ltd.

Societal preferences for distributive justice in the allocation of health care resources: a latent class discrete choice experiment.

Economic theory suggests that resources should be allocated in a way that produces the greatest outputs, on the grounds that maximizing output allows for a redistribution that could benefit everyone. In health care, this is known as QALY (quality-adjusted life-year) maximization. This justification for QALY maximization may not hold, though, as it is difficult to reallocate health. Therefore, the allocation of health care should be seen as a matter of distributive justice as well as efficiency. A discrete choice experiment was undertaken to test consistency with the principles of QALY maximization and to quantify the willingness to trade life-year gains for distributive justice. An empirical ethics process was used to identify attributes that appeared relevant and ethically justified: patient age, severity (decomposed into initial quality and life expectancy), final health state, duration of benefit, and distributional concerns. Only 3% of respondents maximized QALYs with every choice, but scenarios with larger aggregate QALY gains were chosen more often and a majority of respondents maximized QALYs in a majority of their choices. However, respondents also appeared willing to prioritize smaller gains to preferred groups over larger gains to less preferred groups. Marginal analyses found a statistically significant preference for younger patients and a wider distribution of gains, as well as an aversion to patients with the shortest life expectancy or a poor final health state. These results support the existence of an equity-efficiency tradeoff and suggest that well-being could be enhanced by giving priority to programs that best satisfy societal preferences. Societal preferences could be incorporated through the use of explicit equity weights, although more research is required before such weights can be used in priority setting.