Are We Ready for a New Approach to Comparing Coverage and Reimbursement Policies for Medical Nutrition in Key Markets: An ISPOR Special Interest Group Report.

OBJECTIVES: Healthcare policy makers should ensure optimal patient access to medical nutrition (MN) as part of the management of nutrition-related disorders and conditions. Questions remain whether current healthcare policies reflect the clinical and economic benefits of MN. The objective of this article is to characterize coverage and reimbursement of MN, defined as food for special medical purposes/medical food for a diverse set of countries, including Australia, Belgium, Brazil, Canada, China, France, Germany, Hong Kong, Italy, Japan, The Netherlands, Singapore, Spain, United Kingdom, and United States. METHODS: Data sources included published literature and online sources. ISPOR's Nutrition Economics Special Interest Group developed a data collection form to guide data extraction that included reimbursement coverage, years that reimbursement policies were established, and presence of a formal health technology assessment (HTA) for MN technologies. RESULTS: Reimbursement coverage of MN technologies varied across the countries that were reviewed. All but 3 countries limited coverage to specific formulations of products, regardless of demonstrated clinical benefit. The year that reimbursement policies were established varied across countries (ranging from 1984 to 2017), and only 4 countries regularly update policies. France and Brazil are the only countries with a formal HTA process for MN technologies. CONCLUSIONS: Most countries have limited MN reimbursement, have not updated reimbursement policies, and lack HTA for MN technologies. These limitations may lead to suboptimal access to MN technologies where they are indicated to manage nutrition-related disorders and conditions, with the potential of negatively affecting patient and healthcare system outcomes.

The impact of early phase price agreements on prices of orphan drugs.

BACKGROUND: Innovative orphan drugs often have an incremental cost-effectiveness ratio (ICER) which is higher than the maximum threshold for reimbursement. Payers have limited budgets and often cannot pay the full price of a new product, but pharmaceutical and biotechnology companies require a minimum price to satisfy their investors. The objective of this study was to present a possible solution to bridge this pricing gap by having early phase price agreements, which reduce the risk for investors. METHODS: We used a Pricing Model, which determines the minimum (break-even) price of an innovative drug from an investor's perspective. This model is based on economic valuation theory, which uses the expected free cash flows and the required cost of capital. We selected two orphan drugs with a positive clinical assessment and an ICER higsher than the Dutch maximum threshold of €80,000 per QALY gained to use as examples in the model: Spinraza for spinal muscular atrophy and Orkambi for cystic fibrosis. RESULTS: The results show that early pricing agreements before phase III trials can substantially lower the drug price resulting from a lower cost of capital. The minimum price for orphan drugs can be reduced by 27.4%, when cost of capital decreases from 12 to 9%. An additional adjustment of other critical parameters due to early pricing agreements (lower probabilities of phase III failure and lower research and development (R&D) costs) can further reduce the minimal price by 62.8%. CONCLUSION: This study shows that earlier timing of price negotiations resulting in an agreement on drug price can substantially lower the minimal price of orphan drugs for the investor.

An economic assessment of embryo diagnostics (Dx) - the costs of introducing non-invasive embryo diagnostics into IVF standard treatment practices.

BACKGROUND: New techniques in assessing oocytes and embryo quality are currently explored to improve pregnancy and delivery rates per embryo transfer. While a better understanding of embryo quality could help optimize the existing "in vitro fertilization" (IVF) therapy schemes, it is essential to address the economic viability of such technologies in the healthcare setting. METHODS: An Embryo-Dx economic model was constructed to assess the cost-effectiveness of 3 different IVF strategies from a payer's perspective; it compares Embryo-Dx with single embryo transfer (SET) to elective single embryo transfer (eSET) and to double embryo transfer (DET) treatment practices. RESULTS: The introduction of a new non-invasive embryo technology (Embryo-Dx) associated with a cost up to €460 is cost-effective compared to eSET and DET based on the cost per live birth. The model assumed that Embryo-Dx will improve ongoing pregnancy rate/realize an absolute improvement in live births of 9% in this case. CONCLUSIONS: This study shows that improved embryo diagnosis combined with SET may have the potential to reduce the cost per live birth per couple treated in IVF treatment practices. The results of this study are likely more sensitive to changes in the ongoing pregnancy rate and consequently the live birth rate than the diagnosis costs. The introduction of a validated Embryo-Dx technology will further support a move towards increased eSET procedures in IVF clinical practice and vice versa.

Valuation of Medical Innovation Handling with Uncertainty and Risk.

Background: The purpose of this paper is to address how to handle uncertainty when performing an economic valuation of a medical innovation R&D project in orphan diseases from the perspective of the investor. Methods: We describe the specific uncertainty related to cash flows and the cost of capital for innovation in orphan diseases. The uncertainty in cash flows relates to sales, manufacturing and R&D costs, and probabilities of failure for each phase in the clinical trial program. We consider different net present values (NPVs) and higher standard deviations for orphan drugs compared to non-orphan drugs. Results: Numerical case base examples showed the differences in trade-off by an investor for R&D projects with differences in NPV and level of uncertainty. The investor will transfer the additional uncertainty in cash flows in a higher cost of capital. An alternative approach is the application of an "acceptability curve" based on a probabilistic sensitivity analysis, which displays the cumulative probabilities at a range of different values for the NPV. Finally, we consider uncertainty in the cost of capital itself by applying the Capital Asset Pricing Model (CAPM). Conclusions: In this paper, we described various types of uncertainty and explored various approaches to how to handle uncertainty in the economic valuation of medical innovation in orphan diseases. The bridging of health economics with economic valuation theory in the healthcare market is to our knowledge a novel approach for the valuation of medical innovation by investors.

Primary prevention of nephrolithiasis is cost-effective for a national healthcare system.

UNLABELLED: Study Type--Therapy (cost-effectiveness meeting) Level of Evidence 2b. What's known on the subject? and What does the study add? One of the major problems with nephrolithiasis is the high rate of recurrence, which can effect up to 50% of patients over a 5-year period. Patients with recurrent stones are recommended to increase fluid intake based on prospective studies that show a reduction in recurrence rates in patients who intake a high volume of water. Strategies to reduce stones in recurrent stone formers are quite effective with a >50% risk reduction with increased fluid intake alone. Unfortunately, despite a high societal cost and morbidity, there are no prospective studies evaluating the benefit of fluid intake to prevent stone disease in subjects without a prior history of stone but at risk for stones. The budget impact analyses show that prevention of nephrolithiasis can have a significant cost savings for a payer in a healthcare system and reduce the stone burden significantly. Future studies will need to assess the feasibility and effectiveness of such an approach in a population. OBJECTIVE: • To evaluate the impact of primary prevention of stones using a strategy of increased fluid intake. SUBJECTS AND METHODS: • A Markov model was constructed and analysed using Excel to calculate and compare the costs and outcomes for a virtual cohort of subjects with low vs high water intake. • A literature search was used to formulate assumptions for the model including an annual incidence of urolithiasis of 0.032%, annual risk of stone recurrence of 14.4% and 40% risk reduction in subjects with high water intake. • Costs were based on resource utilisation from the Delphi panel and official price lists in France. • Outcomes were based on payer perspective and included direct and indirect costs and loss of work. RESULTS: • The base-case analysis found total cost of urolithiasis is €4267 with direct costs of €2767, including cost of treatment and complications. The annual budget impact for stone disease based on 65 million inhabitants is €590 million for the payer. • The use of high water intake by 100% of the population results in annual cost savings of €273 million and 9265 fewer stones. Even if only 25% of the population is compliant, there is still a cost saving of €68 million and 2316 stones. • The model was evaluated to determine the impact of varying the assumptions by ±10%. For example, when the incidence of stone disease is increased or decreased by 10% then the mean (range) baseline cost will change by €59(531-649) million for the payer and savings will either increase or decrease by €27 (246-300) million. • The largest impact on cost savings occurs when varying risk reduction of water by 10% resulting in either a mean (range) increase or decrease by €35 (238-308) million. • Varying cost of stone management by 10% has an impact of ±€17 million. Varying other factors such as stone recurrence by 10% has only an impact of ±€9 million and varying risk of chronic kidney disease ±€1 million, as they affect only a portion of the population. CONCLUSIONS: • The budget impact analyses show that prevention of nephrolithiasis can have a significant cost savings for a payer in a healthcare system and reduce the stone burden significantly. • Future studies will need to assess the feasibility and effectiveness of such an approach in a population.

An integrated valuation model for payer and investor.

Background: In order to optimize positioning and associated drug price for both payer and investor, it is for a company essential to forecast the potential market access attractiveness for the new drug for different indications at the early onset of the clinical development program. This analysis must include the constraints from the perspective of the payer, but also the biotech companies, who require a minimum drug price to satisfy their investors. This paper aims to provide an Integrated Valuation Model for payer and investor, bridging concepts from health economics and economic valuation reflecting the perspectives of the payer and the investor for a drug in early clinical development phase. The concept is illustrated for a new hypothetical drug (Product X) in advanced breast cancer in 1-line, 2-line, and 3-line position. Methods: The Integrated Valuation Model includes the outcomes of the budget impact model, pricing matrix model, and cost-effectiveness model reflecting the payer's perspective. These models are interacted and linked with a discounted cash flow model in order to reflect also the economic value from the investor's perspective. Results: The maximum price in 1-line position is €269.7 for the payer and the minimum price is €14.7 for the investor, which are unit prices per administration corresponding with treatment regimens for the comparative treatments. In 2-line position, the maximum price is €274.1 for the payer and the minimum price for the investor increases to €184.5 for the investor because of the smaller market size in 2-line position, which leads to a smaller pricing corridor to satisfy both payer and investor. Consequently, Product X has market access attractiveness for both payer and investor in 1-line and 2-line position. However, the minimum price €942.7 in 3-line position for the investor is higher than the maximum price €283.3 for the payer, which means there is no market potential. Conclusion: The practical strategic application of the Integrated Valuation Model is optimization of positioning and price of Product X. Hence, it can be a transparent tool in early-stage development of a compound based on upfront assessment of market access attractiveness for the payer and the investor.

Does the Structure Matter? An External Validation and Health Economic Results Comparison of Event Simulation Approaches in Severe Obesity.

OBJECTIVES: As obesity-associated events impact long-term survival, health economic (HE) modelling is commonly applied, but modelling approaches are diverse. This research aimed to compare the events simulation and the HE outcomes produced by different obesity modelling approaches. METHODS: An external validation, using the Swedish obesity subjects (SOS) study, of three main structural event modelling approaches was performed: (1) continuous body mass index (BMI) approach; (2) risk equation approach; and (3) categorical BMI-related approach. Outcomes evaluated were mortality, cardiovascular events, and type 2 diabetes (T2D) for both the surgery and the control arms. Concordance between modelling results and the SOS study were investigated by different state-of-the-art measurements, and categorized by the grade of deviation observed (grades 1-4 expressing mild, moderate, severe, and very severe deviations). Furthermore, the costs per quality-adjusted life-year (QALY) gained of surgery versus controls were compared. RESULTS: Overall and by study arm, the risk equation approach presented the lowest average grade of deviation (overall grade 2.50; control arm 2.25; surgery arm 2.75), followed by the continuous BMI approach (overall 3.25; control 3.50; surgery 3.00) and by the categorial BMI approach (overall 3.63; control 3.50; surgery 3.75). Considering different confidence interval limits, the costs per QALY gained were fairly comparable between all structural approaches (ranging from £2,055 to £6,206 simulating a lifetime horizon). CONCLUSION: None of the structural approaches provided perfect external event validation, although the risk equation approach showed the lowest overall deviations. The economic outcomes resulting from the three approaches were fairly comparable.

Replication of Published Health Economic Obesity Models: Assessment of Facilitators, Hurdles and Reproduction Success.

OBJECTIVES: This research aims to (1) replicate published health economic models, (2) compare reproduced results with original results, (3) identify facilitators and hurdles to model replicability and determine reproduction success, and (4) suggest model replication reporting standards to enhance model reproducibility, in the context of health economic obesity models. METHODS: Four health economic obesity models simulating an adult UK population were identified, selected for replication, and evaluated using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist. Reproduction results were compared to original results, focusing on cost-effectiveness outcomes, and the resulting reproduction success was assessed by published criteria. Replication facilitators and hurdles were identified and transferred into related reporting standards. RESULTS: All four case studies were state-transition models simulating costs and quality-adjusted life-years (QALYs). Comparing original versus reproduction outcomes, the following deviation ranges were observed: costs - 3.9 to 16.1% (mean over all model simulations 3.78%), QALYs - 3.7 to 2.1% (mean - 0.11%), and average cost-utility ratios - 3.0 to 17.9% (mean 4.28%). Applying different published criteria, an overall reproduction success was observed for three of four models. Key replication facilitators were input data tables and model diagrams, while missing standard deviations and missing formulas for equations were considered as key hurdles. CONCLUSIONS: This study confirms the feasibility of rebuilding health economic obesity models, but minor to major assumptions were needed to fill reporting gaps. Model replications can help to assess the quality of health economic model documentation and can be used to validate current model reporting practices. Simple changes to actual CHEERS reporting criteria may solve identified replication hurdles.

A Meal Replacement Program for the Treatment of Obesity: A Cost-Effectiveness Analysis from the Swiss Payer's Perspective.

BACKGROUND: Obesity is a disease associated with high direct medical costs and high indirect costs resulting from productivity loss. The high prevalence of obesity generates the need for payers to identify cost-effective weight loss approaches. Among various weight management techniques, the OPTI (Optifast®) program is a clinically recognised total meal replacement diet that can lead to significant weight loss and reduction in complications. This study's objective is to assess OPTI program's cost-effectiveness in Switzerland in comparison to "no intervention" and pharmacotherapy. METHODS: An event-driven decision-analytic model was used to estimate the payer's cost savings through the reimbursement of OPTI program over a 1-year period as well as a lifetime in Switzerland. The analysis was performed on a broad population of people with obesity with a body mass index (BMI) higher than 30 kg/m2 following the OPTI program vs two comparators (liraglutide and "no intervention"). The model incorporated a higher risk of complications due to an increased BMI and their related healthcare costs. Data sources included published literature, clinical trials, official Swiss price/tariff lists and national population statistics. The primary perspective was that of a Swiss payer. Scenario analyses - for example, for patients with existing complications (such as myocardial infarction, stroke, type 2 diabetes mellitus) or severe obesity - were conducted to test the robustness of the results. RESULTS: The OPTI program results in cost savings of CHF 20,886 (€ 18,724) and CHF 15,382 (€ 13,790) per person compared with "no intervention" and liraglutide 3 mg, respectively. In addition, OPTI program led to 1.133 and 0.734 quality-adjusted life years (QALYs) gained respectively against its comparators. Scenario analyses showed similar outcomes with cost savings and QALYs gained. CONCLUSION: OPTI program is a dominant strategy compared to "no intervention" and liraglutide 3 mg as it leads to both cost savings and QALY gain. Therefore, reimbursing the OPTI program for patients with obesity would be cost-effective for Swiss payers.

Cost effectiveness of a lidocaine 5% medicated plaster compared with pregabalin for the treatment of postherpetic neuralgia in the UK: a Markov model analysis.

BACKGROUND: Published analyses have demonstrated that the lidocaine (lignocaine) plaster is a cost-effective treatment for postherpetic neuralgia (PHN) relative to gabapentin or pregabalin. However, these analyses have been based on indirect comparisons from placebo-controlled trials, and there is evidence of a discrepancy between the outcomes of direct and indirect analyses. Fortunately, recent publication of the results of a head-to-head trial comparing the lidocaine plaster and pregabalin in patients with PHN or diabetic polyneuropathy allows customization of the existing model to more accurately reflect the relative cost effectiveness of these two products. OBJECTIVE: To assess the cost-effectiveness of the lidocaine 5% medicated plaster compared with pregabalin for the treatment of PHN in the UK primary-care setting. METHODS: A Markov model has been developed to assess the costs and benefits of the lidocaine plaster and pregabalin over a 6-month time horizon for the treatment of patients with PHN who are intolerant to tricyclic antidepressants and in whom analgesics are ineffective or contraindicated. The model structure allows for differences in costs, utilities (derived from published data and from the head-to-head trial) and transition probabilities between the initial 30-day run-in period and maintenance therapy, and also takes account of add-in medication and drugs received by patients discontinuing therapy. The calculation was based on data from the recent head-to-head trial described above. Additional data sources included published literature, discussions with a Delphi panel, official price/tariff lists and national population statistics. The study was conducted from the perspective of the UK National Health Service (NHS). RESULTS: The base-case analysis (1.71 lidocaine plasters per day used in the head-to-head trial for the PHN population) indicated that the total cost of treating PHN patients for 6 months with the lidocaine plaster was pound 980 per patient treated, compared with pound 784 for pregabalin (year of costing 2009). Costs for 1 month without pain and intolerable adverse events (AEs) (modified TWIST analysis) were pound 126 for the lidocaine plaster relative to pregabalin. The average patient treated with the lidocaine plaster experienced 0.321 quality-adjusted life-years (QALYs) over the 6-month period modelled compared with 0.254 QALYs for pregabalin. Quality-of-life benefits were attributed to the favourable AE profile of the lidocaine plaster. Subsequently, the lidocaine plaster cost pound 2925 per QALY gained relative to pregabalin. However, patient level longitudinal data have shown that the actual clinical usage of the lidocaine plaster is 1.1 plasters per day. If this more realistic assumption is used in the model, the total cost for a 6-month treatment period was pound 756 for the lidocaine plaster, which dominated treatment with pregabalin. Scenario analyses and sensitivity analyses had minimal impact on the results, confirming the robustness of the study. The incremental cost-effectiveness ratios for the lidocaine plaster remained well below pound 35,000 per QALY gained in all analyses. CONCLUSION: This analysis showed that the lidocaine 5% medicated plaster is a cost-effective method for obtaining sustained relief of localized neuropathic pain associated with PHN compared with pregabalin in a UK setting, in terms of both the cost per QALY gained and the cost per additional month without symptoms, when used for patients who do not experience sufficient pain relief from standard analgesics.

Cost Effectiveness of Paricalcitol versus a non-selective vitamin D receptor activator for secondary hyperparathyroidism in the UK: a chronic kidney disease markov model.

BACKGROUND: secondary hyperparathyroidism (SHPT) is a common complication of chronic kidney disease (CKD) and a frequent cause of clinically significant bone disease. Non-selective vitamin D receptor (VDR) activator treatment has been used to treat the condition but is ineffective for many patients with hypercalcaemia and hyperphosphataemia and may precipitate worsening of their condition. Compared with non-selective VDR activator treatment, use of the VDR ligand paricalcitol may increase survival and reduce the risk of morbidities in patients with SHPT, which may have health economic consequences. OBJECTIVE: the objective of this study was to determine the cost effectiveness of paricalcitol versus a non-selective VDR activator for the treatment of SHPT in patients with CKD in the UK setting. METHODS: A Markov process model was developed employing data sources from the published literature, paricalcitol clinical trials and observational studies, official UK price/tariff lists and national population statistics. The comparator was alfacalcidol, a non-selective VDR activator medication. The primary perspective of the study was that of the UK National Health Service (NHS). The efficacy outcomes (reductions in SHPT, proteinuria, complications and mortality) were extrapolated to: number of life-years gained (LYG) and number of quality-adjusted life-years (QALYs). Clinical and economic outcomes were discounted at 3.5%. The year of costing for costs determined in the study was 2006. RESULTS: the reference case analysis was a 10-year time horizon, based on a comparison of paricalcitol with a non-selective VDR activator, which is started in CKD stage 3 (moderate reduction in glomerular filtration rate [GFR] with kidney damage) and continued in CKD stage 4 (severe reduction in GFR) and CKD stage 5 (established kidney failure). The use of paricalcitol leads to an additional medical cost of pound3224 ($US5970). The health benefits of paricalcitol lead to an increase in LYG of 0.52 and a gain in QALYs of 0.465. Therefore the use of paricalcitol results in an incremental cost-effectiveness ratio of pound6933/QALY ($US12 840/QALY) from the primary perspective of the NHS. One-way sensitivity analyses and probabilistic sensitivity analyses confirmed the robustness of the model. CONCLUSION: this model showed that the favourable clinical benefit of paricalcitol results in positive short- and long-term health economic benefits. This study suggests that the use of paricalcitol in patients with early CKD may be cost effective from the UK NHS perspective versus non-selective VDR activator medication.

Pricing of orphan drugs in oncology and rare diseases.

Objective: The objective of this paper is to determine an upper price limit for an orphan drug by taken a broader perspective and, including also other monetary and non-monetary values for the society. Methods: This model is based on the expected free cash flows and the required minimum rate of return for the investor. In addition we calculated an innovation premium resulting from cost savings due to the substitution effect and the monetary gain in QALYs of a new medicine. We selected Spinraza®, a first in class drug with only best supportive care as comparator, and Perjeta®, a first in class drug with already an actual treatment as comparator. Results: The results show that Spinraza® leads to an innovation premium of € 78,966 and Perjeta® shows an innovation premium of € 4,388, because there were no cost savings. The analyses show the outcomes are sensitive to discount rate for QALYs. Conclusion: The break-even price from only an investor perspective may not reflect the value of drug from a broader perspective. This study shows drug prices based on an innovation premium may be more representative of the actual value of innovation for the society.

Cost-effectiveness of palivizumab against respiratory syncytial viral infection in high-risk children in Austria.

OBJECTIVE: The aim of this study was to estimate the cost-effectiveness of palivizumab, a monoclonal antibody against severe respiratory syncytial virus infection, in high-risk infants in Austria. METHODS: A decision tree model was developed to determine cost-effectiveness in infants born prematurely (

Cost-effectiveness analysis of a lidocaine 5% medicated plaster compared with gabapentin and pregabalin for treating postherpetic neuralgia: a german perspective.

OBJECTIVE: This study set out to assess the cost effectiveness of using a 5% lidocaine (lignocaine) medicated plaster for the treatment of postherpetic neuralgia (PHN) compared with gabapentin, pregabalin 300 mg/day or 600 mg/day in German primary care. The analysis took the perspective of the Statutory Health Insurance scheme (GKV). METHODS: A Markov model was used to calculate the costs (2007) and benefits of the lidocaine plaster, gabapentin 1800 mg/day and pregabalin 300 or 600 mg/day over a 6-month time horizon in elderly patients with PHN who experienced insufficient pain relief with standard analgesics and could not tolerate or had contraindications to tricyclic antidepressants. The model calculated the cost per quality-adjusted life-year (QALY) gained and the cost per additional month without symptoms or intolerable adverse effects. The majority of transition probabilities were obtained from randomized controlled trials identified from a systematic literature review. Further model inputs, including resource use, concomitant medication and long-term efficacy/adherence data, were obtained from a Delphi panel. Utility values were taken from a previous study and age adjusted. Cost data were obtained from official price tariffs. Mortality, indirect costs and costs associated with inpatient treatment were not considered in the present analysis due to the perspective and time horizon employed. RESULTS: Over the 6-month period modelled, the mean total therapy cost per patient treated with the lidocaine plaster was euro911, compared with euro728 for gabapentin, euro875 for pregabalin 300 mg/day and euro977 for pregabalin 600 mg/day. Treatment with the lidocaine plaster was related to greater numbers of QALYs and more months without symptoms or intolerable adverse effects (mean 0.300 QALYs and 4.06 months per patient) than with gabapentin (mean 0.247 QALYs and 2.72 months), pregabalin 300 mg/day (mean 0.253 QALYs and 3.02 months) or pregabalin 600 mg/day (mean 0.256 QALYs and 3.22 months). The lidocaine plaster cost euro3453/QALY gained and euro137 per additional month without adverse effects or symptoms relative to gabapentin and euro766/QALY and euro35 per month without adverse effects or symptoms relative to pregabalin 300 mg/day. The lidocaine plaster dominated pregabalin 600 mg/day, being less costly and more effective. Probabilistic sensitivity analysis indicated that there is a 99.36% chance that the lidocaine plaster is the most clinically effective treatment considered in the analysis and a 99.09% chance that the lidocaine plaster is the most cost-effective treatment of the four therapies considered in the analysis if the GKV is willing to pay at least euro20 000/QALY gained. Extensive deterministic sensitivity analyses demonstrated that the findings are robust. CONCLUSIONS: The 5% lidocaine-medicated plaster is a cost-effective treatment option for the management of PHN in Germany compared with gabapentin and both 300 and 600 mg/day of pregabalin.

Event simulation and external validation applied in published health economic models for obesity: a systematic review.

INTRODUCTION: This study aims to determine methodological variations in the event simulation approaches of published health economic decision models, in the field of obesity, and to investigate whether their predictiveness and validity were investigated via external event validation techniques, which investigate how well the model reproduces reality. AREAS COVERED: A systematic review identified a total of 87 relevant papers, of which 72 that simulated obesity-associated events were included. Most frequently simulated events were coronary heart disease (≈ 83%), type 2 diabetes (≈ 74%), and stroke (≈ 66%). Only for ten published model-based health economic assessments in obesity an external event validation was performed (14%; 10 of 72), and only for one the predictiveness and validity of the event simulation was investigated in a cohort of obese subjects. EXPERT COMMENTARY: We identified a wide range of obesity related event simulation approaches. Published obesity models lack information on the predictive quality and validity of the applied event simulation approaches. Further work on comparing and validating these event simulation approaches is required to investigate their predictiveness and validity, which will offer guidance future modelling in the field of obesity.

A health economic model to assess the cost-effectiveness of OPTIFAST for the treatment of obesity in the United States.

OBJECTIVES: Obesity is associated with high direct medical costs and indirect costs resulting from productivity loss. The high prevalence of obesity generates a justified need to identify cost-effective weight loss approaches from a payer's perspective. Within the variety of weight management techniques, OPTIFAST is a clinically recognized and scientifically proven total meal replacement Low Calorie Diet that provides meaningful results in terms of weight loss and reduction in comorbidities. The objective of this study is assess potential cost-savings of the OPTIFAST program in the US, as compared to "no intervention" and pharmacotherapy. METHODS: An event-driven decision analytic model was used to estimate payer's cost-savings from reimbursement of the 1-year OPTIFAST program over 3 years in the US. The analysis was performed for the broad population of obese persons (BMI >30 kg/m2) undergoing the OPTIFAST program vs liraglutide 3 mg, naltrexone/bupropion and vs "no intervention". The model included the risk of complications related to increased BMI. Data sources included published literature, clinical trials, official US price/tariff lists, and national population statistics. The primary perspective was that of a US payer; costs were provided in 2016 US dollars. RESULTS: OPTIFAST leads over a period of 3 years to cost-savings of USD 9,285 per class I and II obese patient (BMI 30-39.9 kg/m2) as compared to liraglutide and USD 685 as compared to naltrexone/bupropion. In the same time perspective, the OPTIFAST program leads to a reduction of cost of obesity complications of USD 1,951 as compared to "no intervention", with the incremental cost-effectiveness ratio of USD 6,475 per QALY. Scenario analyses also show substantial cost-savings in patients with class III obesity (BMI ≥ 40.0 kg/m2) and patients with obesity (BMI = 30-39.9 kg/m2) and type 2 diabetes vs all three previous comparators and bariatric surgery. CONCLUSIONS: Reimbursing OPTIFAST leads to meaningful cost-savings for US payers as compared with "no intervention" and liraglutide and naltrexone/bupropion in obese patients. Similar results can be expected in matching healthcare settings of other countries. Moreover, OPTIFAST has additional clinical and economic advantages through very low complication and adverse events rates.

Cost-effectiveness of a lidocaine 5% medicated plaster relative to gabapentin for postherpetic neuralgia in the United Kingdom.

BACKGROUND: Approximately 50% of elderly patients develop postherpetic neuralgia (PHN) after herpes zoster infection (shingles). A lidocaine 5% medicated plaster marketed in the United Kingdom in January 2007 has been shown to be an effective topical treatment for PHN with minimal risk of systemic adverse effects. OBJECTIVE: This paper assessed the cost-effectiveness of using a lidocaine plaster in place of gabapentin in English primary care practice to treat those PHN patients who had insufficient pain relief with standard analgesics and could not tolerate or had contraindications to tricyclic antidepressants (TCAs). The analysis took the perspective of the National Health Service (NHS). METHODS: The costs and benefits of gabapentin and the lidocaine plaster were calculated over a 6-month time horizon using a Markov model. The model structure allowed for differences in costs, utilities, and transition probabilities between the initial 30-day run-in period and maintenance therapy and also accounted for add-in medications and drugs received by patients who discontinued therapy. Most transition probabilities were based on non-head-to-head clinical trials identified through a systematic review. Data on resource utilization, discontinuation rates, and add-in or switch medications were obtained from a Delphi panel; cost data were from official price tariffs. Published utilities were adjusted for age and were supplemented and validated by the Delphi panel. RESULTS: Six months of therapy with the lidocaine plaster cost pound 549 per patient, compared with pound 718 for gabapentin, and generated 0.05 more quality-adjusted life-years (QALYs). The lidocaine plaster therefore dominated gabapentin (95% CI, dominant- pound 2163/QALY gained). Probabilistic sensitivity analysis showed that there was a 90.15% chance that the lidocaine plaster was both less costly and more effective than gabapentin and a 99.99% chance that it cost < pound 20,000/QALY relative to gabapentin. Extensive deterministic sensitivity analyses confirmed the robustness of the conclusions. CONCLUSION: This study found that the lidocaine 5% medicated plaster was a cost-effective alternative to gabapentin for PHN patients who were intolerant to TCAs and in whom analgesics were ineffective, from the perspective of the NHS.

Cost effectiveness of palivizumab for respiratory syncytial virus prophylaxis in high-risk children: a UK analysis.

OBJECTIVE: To assess the cost effectiveness of palivizumab (a preventative treatment against severe respiratory syncytial virus [RSV] infection) in children at high risk of hospitalisation, i.e. preterm infants < or = 35 weeks gestation, children with bronchopulmonary dysplasia (BPD) and children with congenital heart disease (CHD). METHODS: A decision tree model was developed employing data sources from the published literature, palivizumab clinical trials, official UK price/tariff lists and national population statistics. The comparator was no prophylaxis. The primary perspective of the study was that of the UK NHS. In a societal perspective scenario analysis, the future lost productivity of a child resulting from RSV-related mortality (indirect costs) was also included. The cost of administration of palivizumab, hospital care for RSV infections and the cost of asthma treatment were included. The analysis was based on a lifetime follow-up period in order to capture the impact of palivizumab on long-term morbidity and mortality resulting from an RSV infection. The primary efficacy outcome in the palivizumab clinical trials was the number of RSV hospitalisations avoided, which was extrapolated to effectiveness outcomes, i.e. number of life-years gained and number of QALYs. Costs and effects were discounted by 3.5%. RESULTS: In preterm infants and children with BPD, prophylaxis with palivizumab compared with no prophylaxis had an incremental cost-effectiveness ratio (ICER) of 7042 pounds/QALY without discounting outcomes, increasing to 16,720 pounds/QALY after discounting. In babies with CHD, the use of palivizumab resulted in an ICER of 2427 pounds/QALY without discounting outcomes and 6664 pounds/QALY after discounting. One-way sensitivity analyses and probabilistic sensitivity analyses confirmed the robustness of the model. A scenario analysis showed that the inclusion of indirect costs leads to further improvement in the cost-effectiveness outcomes for palivizumab. CONCLUSION: This study suggests that palivizumab prophylaxis against severe RSV infection in children at high risk may be cost effective from the NHS perspective (vs no prophylaxis), and that the positive clinical and economic benefits may persist beyond one RSV season.

Pricing matrix model: dealing with uncertainty.

A previous publication in this journal showed that the pricing matrix model (PMM) allows an assessment of the pricing potential of a new innovative product. When the PMM is going to be used for the determination of a drug price for a new drug in the strategic product planning process, it is important that this methodology is reliable. In the initial paper the PMM only yielded an expected price for the new antidepressant without generating an estimate of the probability that the new drug would indeed be listed at this expected price. In this manuscript we present various methodologies to deal with uncertainty in the PMM. We introduce the concept of price acceptability curves. The conclusion of this paper is that the incorporation of uncertainty into the PMM will lead to a more accurate assessment of the pricing potential of a new drug.