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.

Improving the understanding of how patients with non-dystrophic myotonia are selected for myotonia treatment with mexiletine (NaMuscla): outcomes of treatment impact using a European Delphi panel.

BACKGROUND: Non-dystrophic myotonias (NDMs) comprise muscle chloride and sodium channelopathies due to genetic defects of the CLCN1- and SCN4A-channels. No licensed antimyotonic treatment has been available until approval of mexiletine (NaMuscla®) for adult patients by the EMA in December 2018. This Delphi panel aimed to understand how outcomes of the pivotal phase III Mexiletine study (MYOMEX) translate to real world practice and investigate health resource use, quality of life and the natural history of NDM to support economic modelling and facilitate patient access. METHODS: Nine clinical experts in treating NDM took part in a two-round Delphi panel. Their knowledge of NDM and previous use of mexiletine as an off-label treatment prior to NaMuscla's approval ensured they could provide both qualitative context and quantitative estimates to support economic modelling comparing mexiletine (NaMuscla) to best supportive care. Consensus in four key areas was sought: healthcare resource utilization (HRU), treatment with mexiletine (NaMuscla), patient quality of life (QoL), and the natural history of disease. Concept questions were also asked, considering perceptions on the feasibility of mapping the validated Individualized Neuromuscular Quality of Life (INQoL) instrument to the generic EQ-5D™, and the potential impact on caregiver QoL. RESULTS: Consensus was achieved for key questions including the average long-term dosage of mexiletine (NaMuscla) in practice, the criteria for eligibility of myotonia treatment, the clinical importance of QoL outcomes in MYOMEX, the higher proportion of patients with increased QoL, and the reduction in the need for mental health resources for patients receiving mexiletine (NaMuscla). While consensus was not achieved for other questions, the results demonstrated that most experts felt mexiletine (NaMuscla) reduced the need for HRU and was expected to improve QoL. The QoL mapping exercise suggested that it is feasible to map domains of INQoL to EQ-5D. Points of interest for future research were identified, including that mexiletine (NaMuscla) may slow the annual decrease in QoL of patients over their lifetime, and a significant negative impact on QoL for some caregivers. CONCLUSIONS: This project successfully provided data from an informed group of clinical experts, complementing the currently available clinical trial data for mexiletine (NaMuscla) to support patient access decisions.

Implementing Guidelines: The Cost and Clinical Impact of Anticoagulants in the UK Atrial Fibrillation Population.

BACKGROUND: Updated treatment guidelines for atrial fibrillation (AF) have been released by the National Institute for Health and Care Excellence (NICE) in the UK, and highlight a current shortfall in the prescription of anticoagulants to patients with AF for stroke prevention. OBJECTIVE: To design a budget impact model as a planning tool for UK Clinical Commissioning Groups (CCGs) looking to budget for greater use of anticoagulants in the AF population. METHODS: An Excel® model was developed to estimate the five-year impact of gradually treating all eligible patients with AF who are currently not being prescribed anticoagulants, both in terms of the effect on key clinical outcomes (strokes, major bleeds and mortality) and the associated financial impact. RESULTS: For a population of 251,693 (average CCG size) with an estimated 2626 prevalent patients and an additional 546 incident cases annually, the model estimated that increasing the proportion of the eligible AF patient population receiving anticoagulation by a fraction would require an additional budget of GBP139,961 in Year 1 to treat an additional 314 patients. This would rise to GBP1,004,900 in Year 5 to treat an additional 2242 patients, with all eligible patients treated by this year. The price year was 2014. Over the 5-year timeframe, this could lead to the prevention of 24 strokes and 29 deaths, with an increase of 31 major bleeds. CONCLUSIONS: The clinical benefits of appropriate anticoagulation are widely recognised; however, full implementation can be difficult and costly. Therefore, the development of models can support the planning process by facilitating discussion among stakeholders on how best they can reach full implementation. The model is flexible and can be adapted to suit different payers.

The cost-effectiveness of diagnostic cardiac imaging for stable coronary artery disease.

Early and accurate diagnosis of stable coronary artery disease (CAD) is crucial to reduce morbidity, mortality and healthcare costs. This critical appraisal of health-economic literature concerning non-invasive diagnostic cardiac imaging aims to summarize current approaches to economic evaluation of diagnostic cardiac imaging and associated procedural risks, inform cardiologists how to use economic analyses for decision-making, highlight areas where new information could strengthen the economic evaluation and shed light on cost-effective approaches to diagnose stable CAD. Economic analysis can support cardiologists' decision-making. Current economic evidence in the field does not provide sufficient information to guide the choice among different imaging modalities or strategies for each patient. Available economic analyses suggest that computed tomography coronary angiography (CTCA) is a cost-effective approach to rule out CAD prior to invasive coronary angiography in patients with low to intermediate pre-test probability of disease and that stress imaging modalities may be cost-effective at variable pre-test probabilities.

Management of patients with transient ischemic attack: insight from real-life clinical practice in Europe and the United States.

OBJECTIVE: Transient ischemic attack (TIA) is a serious condition which should be considered on the same spectrum as other conditions involving brain ischemia. Efficient management of these patients is therefore critical. The aim of this research was to gain insights into 'real-world' global trends of the current management approaches for patients with suspected and diagnosed TIA, and highlight the unmet need and areas of improvement to ensure effective management of this patient group. RESEARCH DESIGN AND METHODS: Tele-interviews were conducted with 120 physicians and five operational managers across France, Germany, Italy, Spain, UK, and the US including stakeholders from primary care group practice, those with hospital responsibilities (ER physician and Neurologists), or from home health agencies. Information from the interviewees regarding the management of patients with TIA (including entrance into the clinical pathway, diagnosis, and treatment) were obtained and analyzed qualitatively. RESULTS: The majority of patients with suspected TIA were reported to enter the clinical pathway via the GP or ER, irrespective of country. Once initially seen, the neurologist then plays a central role in the diagnosis, treatment and follow-up of the patients. Although a number of tests are routinely employed, interviewees reported that streamlining and simplification of diagnosis, faster initiation of treatment, improved efficacy and fewer side-effects with treatment were needed for patients with suspected TIA. The study is designed to provide a directional indication of the current situation rather than strong, quantitative conclusions, given limitations of the small sample size and subjective nature of the data. CONCLUSIONS: The importance of correct management of patients with TIA is becoming increasingly recognized by physicians. Improved education for patients regarding symptom recognition and severity is required along with a standardized diagnostic process. These would enable correct and fast diagnosis and initiation of treatment thereby reducing the risk of further events.

Economic impact of using additional diagnostic tests to better select patients with stroke for intravenous thrombolysis in the United Kingdom.

BACKGROUND: Eligibility for thrombolysis as an acute stroke treatment is determined through the use of unenhanced noncontrast computed tomography (CT), time since stroke onset, and patient history. Assessing penumbral patterns, which can be examined only through the use of diagnostic technologies such as magnetic resonance imaging (MRI) and perfusion CT (CTP), may be able to better select patients for thrombolysis. However, trade-offs in terms of administration time and cost may affect the value of using these diagnostic studies. OBJECTIVE: We examined the trade-offs among patient selection via usual care with CT, usual care plus MRI using diffusion-weighted and perfusion imaging, and usual care plus CTP for their effect on costs and outcomes when diagnosing stroke and selecting candidates for thrombolysis in the United Kingdom. METHODS: A decision-analytic model was developed. Efficacy and utilities were obtained from published studies. Costs were obtained from standard UK costing sources and were supplemented with data from the published literature. Outcomes included a favorable outcome (modified Rankin Scale score <2), costs, life-years, quality-adjusted life-years, and incremental cost-effectiveness ratios. RESULTS: Compared with usual care selection, adding CTP or MRI to better select patients for thrombolysis reduced the number of patients receiving thrombolysis by 9 and 14.6 per 1000 patients treated, respectively, while improving favorable outcome (19.2 and 17.6 per 1000 patients treated, respectively). In both scenarios, costs were decreased slightly. Both CTP and MRI selection were cost saving (more efficacious and less costly) compared with unenhanced CT selection; CTP selection was found to dominate MRI selection. CONCLUSIONS: Adding diagnostic tests such as CTP and MRI to select UK patients for thrombolysis may be a good value for the money and may improve patient outcomes. If a preferred diagnostic test had to be chosen based on economic value, CTP might be the best compromise between unenhanced CT selection and MRI selection.

The Incidence, Prevalence, and Mortality of Stroke in France, Germany, Italy, Spain, the UK, and the US: A Literature Review.

Background. Although the burden of stroke in terms of mortality and disability has been well documented in previous years, data after 2000 are limited. Therefore, the aim of this paper was to identify the epidemiology of stroke in the US and EU5 nations from data published in 2000 and later. Methods. Data from literature databases and online sources were collated to identify information relating to the incidence, prevalence, and mortality of stroke from the year 2000 onwards. Results and Conclusions. Twenty-three data sources were identified. The incidence of and mortality due to stroke both increase with age and are greater in males compared to females. Stroke is a common problem and likely to worsen in the US and EU5 as their populations age. However, pre-2000 trends of decreasing stroke mortality over time have continued after 2000, reflecting a consistent improvement in the treatment and care of patients with stroke.