Brentuximab Vedotin Plus CHP in Frontline sALCL: Adjusted Estimates of Efficacy and Cost-Effectiveness Removing the Effects of Re-Treatment with Brentuximab Vedotin.

BACKGROUND: In the randomised controlled trial ECHELON-2 (NCT01777152; January 2013), brentuximab vedotin (BV) plus cyclophosphamide, doxorubicin and prednisone (CHP) demonstrated improved efficacy compared with CHOP (CHP and vincristine) in frontline CD30+ peripheral T-cell lymphoma (PTCL), an aggressive cancer with poor survival. In ECHELON-2, 70% of patients had systemic anaplastic large cell lymphoma (sALCL), a subtype of PTCL. Of sALCL patients who progressed from BV+CHP and CHOP, 36% (n = 17) and 56% (n = 36) received subsequent BV-containing therapy, respectively. As BV re-treatment was not funded in England at the time, our objective was to estimate adjusted efficacy and cost-effectiveness by excluding BV re-treatment from BV+CHP. METHODS: To remove the effects of BV re-treatment, the inverse probability of censoring weights (IPCW) and two-stage estimator (TSE) approaches, with and without re-censoring, were applied to overall survival (OS) in the BV+CHP arm of the ECHELON-2 sALCL population. Cost-effectiveness was determined in a three-state partitioned survival (PartSA) model from the perspective of the National Health Service (NHS) in England. RESULTS: The unadjusted hazard ratio (HR) for death in patients with sALCL with BV+CHP versus CHOP was 0.54 (95% CI 0.34, 0.87; p = 0.011). The model base case used TSE analysis without re-censoring, which provided an adjusted HR for death of 0.55 (95% CI 0.33, 0.86; p = 0.014). Incremental cost-effectiveness ratios (ICERs) including and excluding re-treatment with BV were £29,760/QALY and £27,761/QALY, respectively. CONCLUSION: TSE without re-censoring provided the most clinically plausible estimate of survival whilst retaining sufficient information for OS extrapolation. After adjustment for BV re-treatment, BV+CHP remains an efficacious and cost-effective treatment in frontline sALCL compared with CHOP.

The cost-effectiveness of brigatinib in adult patients with ALK inhibitor-naive ALK-positive non-small cell lung cancer from a US perspective.

BACKGROUND: The discovery of specific oncogenic drivers in non-small cell lung cancer (NSCLC) has led to the development of highly targeted anaplastic lymphoma kinase tyrosine kinase inhibitors (ALKis). Brigatinib is a next-generation ALKi associated with prolonged progression-free survival in patients with ALKi-naive ALK+ NSCLC. OBJECTIVE: To estimate the cost-effectiveness of brigatinib compared with crizotinib and alectinib in patients with ALKi-naive ALK+ NSCLC, from a US payer perspective. METHODS: A lifetime area under the curve-partitioned survival model with 4 health states was used to evaluate the relative cost-effectiveness of brigatinib in the ALKi-naive ALK+ NSCLC setting. Brigatinib was compared with crizotinib within a cost-effectiveness framework and compared with alectinib in a cost-comparison framework, where all efficacy outcomes were assumed equal. The efficacy of brigatinib and crizotinib was informed by the ALTA-1L trial, and an indirect treatment comparison was performed to inform the efficacy of brigatinib vs alectinib owing to a lack of head-to-head data. Costs were derived from public sources. The main outcomes of the model were total costs, quality-adjusted life-years (QALYs), life-years, and incremental cost-effectiveness ratios. Univariate and probabilistic sensitivity analyses, in addition to multiple scenario analyses, were conducted to assess the robustness of the model outcomes. RESULTS: The improved outcomes observed in ALTA-1L translated into QALY gains (+0.97) in the comparison of brigatinib vs crizotinib. The superior efficacy profile was associated with increased time on treatment with brigatinib, which drove the increase in costs vs crizotinib (+$210,519). The resulting base-case incremental cost-effectiveness ratio was $217,607/QALY gained. Compared with alectinib, brigatinib was associated with a cost difference of -$8,546. Sensitivity analysis suggested that extrapolation of overall survival, the assumptions relating to time on treatment, and subsequent therapy costs were the most influential determinants of results. Probabilistic sensitivity analysis suggested brigatinib had the highest probability of being cost-effective beyond willingness-to-pay thresholds of $236,000 per QALY vs crizotinib and alectinib. CONCLUSIONS: At list prices and under base-case assumptions in the current analysis, brigatinib was associated with cost-savings vs alectinib, and QALY gains but at higher costs vs crizotinib. Additional research into the real-world efficacy of ALKis is warranted to further understand the comparative cost-effectiveness of these therapies. DISCLOSURES: Ms Cranmer and Ms Kearns are employees of Takeda UK Ltd. Dr Young is a former employee of Takeda Pharmaceuticals America, Inc. Dr Humphries is an employee of Takeda Pharmaceuticals U.S.A., Inc. Mr Trueman is an employee of Source Health Economics, the consultancy company that provided health economic and writing services. This work was funded by ARIAD Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited. Work by Source Health Economics was funded by ARIAD Pharmaceuticals, Inc. Professional medical writing assistance was provided by Phillipa White, of Source Health Economics, and funded by ARIAD Pharmaceuticals, Inc.

Cost Effectiveness of Inclisiran in Atherosclerotic Cardiovascular Patients with Elevated Low-Density Lipoprotein Cholesterol Despite Statin Use: A Threshold Analysis.

BACKGROUND: Inclisiran is a novel, cholesterol-lowering therapy, with a long duration of effect, administered every 6 months (subcutaneously by a healthcare professional). In the ORION-10 trial in US patients with atherosclerotic cardiovascular disease (ASCVD) in addition to maximum tolerated statins, with or without ezetimibe, inclisiran demonstrated statistically significant reductions in low-density lipoprotein cholesterol (LDL-C) of up to 51%. This is the first peer-reviewed publication to investigate the price at which inclisiran is cost effective in the US. OBJECTIVE: The aim of this study was to determine the maximum price at which inclisiran is cost effective in addition to standard of care, in US patients with ASCVD, versus standard of care alone, at different willingness-to-pay thresholds. DESIGN, SETTING AND PARTICIPANTS: A lifetime Markov model from the US health system perspective, including 15 health states, was used to evaluate the cost effectiveness of inclisiran. The following states were separated by time from a previous cardiovascular event (0-1 years, 1-2 years, 2+ years ['stable']): initial, unstable angina, myocardial infarction, and stroke. Additional states included revascularization and death (cardiovascular or non-cardiovascular causes). Baseline risk of cardivoascular events were from US database sources or published literature. Reductions in LDL-C from inclisiran were from the ORION-10 trial. LDL-C reduction was used to adjust baseline risk of cardiovascular events, based on established relationships between 1 mmol/L reduction in LDL-C and decreases in cardiovascular events, from the Cholesterol Treatment Trialists studies. The population included adults with a history of ASCVD, and LDL-C ≥ 70 mg/dL, despite maximum tolerated doses of statin therapy. INTERVENTIONS: Inclisiran as an adjunct to standard of care, compared with standard of care alone. MAIN OUTCOMES AND MEASURES: The threshold price of inclisiran. RESULTS: Inclisiran as an adjunct to standard of care resulted in threshold annual inclisiran prices of $6383, $9973, and $13,563 at willingness-to-pay thresholds of $50,000, $100,000, and $150,000 per quality-adjusted life-year, respectively. Probabilistic sensitivity analysis showed that at a threshold of $100,000 per QALY, inclisiran had a 100% probability of being cost effective, with an annual price below $9000. At the publicly available price of $3250 per dose, inclisiran was found to have an incremental cost-effectiveness ratio just above the $50,000 per QALY threshold, of $51,686. CONCLUSIONS AND RELEVANCE: This study identified the price at which inclisiran is cost effective for the US health system, at generally accepted willingness-to-pay thresholds.

The Cost-Effectiveness of Lenvatinib in the Treatment of Advanced or Unresectable Hepatocellular Carcinoma from a Canadian Perspective.

Lenvatinib is an oral multikinase inhibitor indicated for the first-line treatment of unresectable hepatocellular carcinoma (uHCC). In the Phase III REFLECT trial, lenvatinib was noninferior in the primary endpoint of overall survival versus sorafenib, the only systemic therapy funded in Canada prior to the introduction of lenvatinib. Lenvatinib also demonstrated statistically significant improvement compared to sorafenib in secondary endpoint progression-free survival, time to progression, and objective response rate. The aim of this analysis was to estimate the cost-effectiveness of lenvatinib versus sorafenib for the first-line treatment of patients with uHCC from a Canadian perspective. A cost-utility analysis was conducted using partitioned survival modelling, with health states representing progression-free disease, progressed disease, and death. Health effects were measured using quality-adjusted life years (QALYs), and costs were represented in Canadian dollars. Clinical inputs were derived from the REFLECT trial, with outcomes extrapolated using parametric survival models. EQ-5D data collected in REFLECT were used to determine health state utility values, and estimates of resource use came from a survey of clinicians. The model predicted incremental costs of-$5,021 and incremental QALYs of 0.17, making lenvatinib dominant over sorafenib. The model demonstrates lenvatinib to be a cost-effective use of resources versus sorafenib in Canada for the treatment of uHCC. Overall costs are lower compared with sorafenib, while health benefits are greater, with modelled progression-free and overall survival extended by 4.1 and 2.6 months in the lenvatinib arm, respectively.

The clinical and cost-effectiveness of supplemental parenteral nutrition in oncology.

BACKGROUND: Clinical guidelines recommend that parenteral nutrition (PN) is added to enteral nutrition (EN; supplemental parenteral nutrition (SPN)) in order to meet energy and protein needs in patients with cancer when EN alone is insufficient. However, although cancer-related malnutrition is common, there is poor awareness of the value of nutritional care, resulting in SPN being chronically underused. METHODS: We performed a targeted literature review and exploratory cost-utility analysis to gather evidence on the clinical effectiveness of SPN, and to estimate the potential cost-effectiveness of SPN versus EN alone in an example cancer setting. RESULTS: The literature review identified studies linking SPN with malnutrition markers, and studies linking malnutrition markers with clinical outcomes. SPN was linked to improvements in body mass index (BMI), fat-free mass, phase angle (PhA) and prealbumin. Of these markers, BMI and PhA were strong predictors of survival. By combining published data, we generated indirect estimates of the overall survival HR associated with SPN; these ranged from 0.80 to 0.99 (mode 0.87). In patients with Stage IV inoperable pancreatic cancer, the incremental cost-effectiveness ratio versus EN alone was estimated to be £41 350 or £91 501 depending on whether nursing and home delivery costs for EN and SPN were combined or provided separately. CONCLUSION: Despite a lack of direct evidence, the results of the literature review demonstrate that SPN may provide important clinical and quality of life benefits to patients with cancer. The potential for any improvement in outcomes in the modelled patient population is very limited, so cost-effectiveness may be greater in patients with less severe disease and other types of cancer.

An Economic Evaluation of Voretigene Neparvovec for the Treatment of Biallelic RPE65-Mediated Inherited Retinal Dystrophies in the UK.

INTRODUCTION: Voretigene neparvovec (VN) is a gene therapy and the first approved pharmacological treatment for biallelic RPE65-mediated inherited retinal dystrophies (IRD), a rare condition that starts in early life and causes vision to progressively deteriorate towards complete blindness. In a phase III trial, treatment with VN significantly improved functional vision and visual function, and in October 2019 the National Institute for Health and Care Excellence (NICE) Highly Specialised Technologies (HST) process recommended VN for patients in England and Wales. We assessed the cost-effectiveness of VN compared with best supportive care (BSC) in individuals with biallelic RPE65-mediated IRD in the UK. METHODS: A Markov model was developed to estimate the incremental cost per quality-adjusted life-year (QALY) gained for VN compared with BSC, from the perspective of the UK National Health Service and Personal Social Services. Phase III trial data were used to inform transition probabilities up to year 1, after which the treatment effect was assumed to be maintained for 40 years, followed by a decline in vision. A bespoke elicitation exercise involving clinical experts, patients and carers was conducted to estimate utility values for each model health state. RESULTS: At list price, VN is associated with incremental costs of £612,404 and incremental QALYs of 6.4, resulting in an incremental cost-effectiveness ratio (ICER) of £95,072 per QALY gained. Voretigene neparvovec is associated with a significant undiscounted QALY gain (20.5) and is therefore eligible for additional QALY weighting under the NICE HST process; an ICER of up to £205,000 per QALY gained could be considered cost-effective under this framework. CONCLUSION: The results of the model show VN to be a cost-effective use of healthcare resources in the UK at list price. The availability of a commercial discount in the UK (as considered in the NICE appraisal) means that in reality the ICER will be even lower. Plain language summary available for this article.

Cost-effectiveness of sacubitril/valsartan in the treatment of heart failure with reduced ejection fraction.

OBJECTIVE: Chronic heart failure with reduced ejection fraction (HF-REF) represents a major public health issue and is associated with considerable morbidity and mortality. We evaluated the cost-effectiveness of sacubitril/valsartan (formerly LCZ696) compared with an ACE inhibitor (ACEI) (enalapril) in the treatment of HF-REF from the perspective of healthcare providers in the UK, Denmark and Colombia. METHODS: A cost-utility analysis was performed based on data from a multinational, Phase III randomised controlled trial. A decision-analytic model was developed based on a series of regression models, which extrapolated health-related quality of life, hospitalisation rates and survival over a lifetime horizon. The primary outcome was the incremental cost-effectiveness ratio (ICER). RESULTS: In the UK, the cost per quality-adjusted life-year (QALY) gained for sacubitril/valsartan (using cardiovascular mortality) was £17 100 (€20 400) versus enalapril. In Denmark, the ICER for sacubitril/valsartan was Kr 174 000 (€22 600). In Colombia, the ICER was COP$39.5 million (€11 200) per QALY gained. Deterministic sensitivity analysis showed that results were most sensitive to the extrapolation of mortality, duration of treatment effect and time horizon, but were robust to other structural changes, with most scenarios associated with ICERs below the willingness-to-pay threshold for all three country settings. Probabilistic sensitivity analysis suggested the probability that sacubitril/valsartan was cost-effective at conventional willingness-to-pay thresholds was 68%-94% in the UK, 84% in Denmark and 95% in Colombia. CONCLUSIONS: Our analysis suggests that, in all three countries, sacubitril/valsartan is likely to be cost-effective compared with an ACEI (the current standard of care) in patients with HF-REF.

Cost-effectiveness of sacubitril/valsartan in chronic heart-failure patients with reduced ejection fraction.

AIMS: We aimed to assess the cost effectiveness of sacubitril/valsartan compared to angiotensin-converting enzyme inhibitors (ACEIs) for the treatment of individuals with chronic heart failure and reduced-ejection fraction (HFrEF) from the perspective of the Swiss health care system. METHODS: The cost-effectiveness analysis was implemented as a lifelong regression-based cohort model. We compared sacubitril/valsartan with enalapril in chronic heart failure patients with HFrEF and New York-Heart Association Functional Classification II-IV symptoms. Regression models based on the randomised clinical phase III PARADIGM-HF trials were used to predict events (all-cause mortality, hospitalisations, adverse events and quality of life) for each treatment strategy modelled over the lifetime horizon, with adjustments for patient characteristics. Unit costs were obtained from Swiss public sources for the year 2014, and costs and effects were discounted by 3%. The main outcome of interest was the incremental cost-effectiveness ratio (ICER), expressed as cost per quality-adjusted life years (QALYs) gained. Deterministic sensitivity analysis (DSA) and scenario and probabilistic sensitivity analysis (PSA) were performed. RESULTS: In the base-case analysis, the sacubitril/valsartan strategy showed a decrease in the number of hospitalisations (6.0% per year absolute reduction) and lifetime hospital costs by 8.0% (discounted) when compared with enalapril. Sacubitril/valsartan was predicted to improve overall and quality-adjusted survival by 0.50 years and 0.42 QALYs, respectively. Additional net-total costs were CHF 10 926. This led to an ICER of CHF 25 684. In PSA, the probability of sacubitril/valsartan being cost-effective at thresholds of CHF 50 000 was 99.0%. CONCLUSION: The treatment of HFrEF patients with sacubitril/valsartan versus enalapril is cost effective, if a willingness-to-pay threshold of CHF 50 000 per QALY gained ratio is assumed.

Current recommendations on the estimation of transition probabilities in Markov cohort models for use in health care decision-making: a targeted literature review.

OBJECTIVE: Although Markov cohort models represent one of the most common forms of decision-analytic models used in health care decision-making, correct implementation of such models requires reliable estimation of transition probabilities. This study sought to identify consensus statements or guidelines that detail how such transition probability matrices should be estimated. METHODS: A literature review was performed to identify relevant publications in the following databases: Medline, Embase, the Cochrane Library, and PubMed. Electronic searches were supplemented by manual-searches of health technology assessment (HTA) websites in Australia, Belgium, Canada, France, Germany, Ireland, Norway, Portugal, Sweden, and the UK. One reviewer assessed studies for eligibility. RESULTS: Of the 1,931 citations identified in the electronic searches, no studies met the inclusion criteria for full-text review, and no guidelines on transition probabilities in Markov models were identified. Manual-searching of the websites of HTA agencies identified ten guidelines on economic evaluations (Australia, Belgium, Canada, France, Germany, Ireland, Norway, Portugal, Sweden, and UK). All identified guidelines provided general guidance on how to develop economic models, but none provided guidance on the calculation of transition probabilities. One relevant publication was identified following review of the reference lists of HTA agency guidelines: the International Society for Pharmacoeconomics and Outcomes Research taskforce guidance. This provided limited guidance on the use of rates and probabilities. CONCLUSIONS: There is limited formal guidance available on the estimation of transition probabilities for use in decision-analytic models. Given the increasing importance of cost-effectiveness analysis in the decision-making processes of HTA bodies and other medical decision-makers, there is a need for additional guidance to inform a more consistent approach to decision-analytic modeling. Further research should be done to develop more detailed guidelines on the estimation of transition probabilities.

Challenges Associated with Estimating Utility in Wet Age-Related Macular Degeneration: A Novel Regression Analysis to Capture the Bilateral Nature of the Disease.

INTRODUCTION: The estimation of utility values for the economic evaluation of therapies for wet age-related macular degeneration (AMD) is a particular challenge. Previous economic models in wet AMD have been criticized for failing to capture the bilateral nature of wet AMD by modelling visual acuity (VA) and utility values associated with the better-seeing eye only. METHODS: Here we present a de novo regression analysis using generalized estimating equations (GEE) applied to a previous dataset of time trade-off (TTO)-derived utility values from a sample of the UK population that wore contact lenses to simulate visual deterioration in wet AMD. This analysis allows utility values to be estimated as a function of VA in both the better-seeing eye (BSE) and worse-seeing eye (WSE). RESULTS: VAs in both the BSE and WSE were found to be statistically significant (p < 0.05) when regressed separately. When included without an interaction term, only the coefficient for VA in the BSE was significant (p = 0.04), but when an interaction term between VA in the BSE and WSE was included, only the constant term (mean TTO utility value) was significant, potentially a result of the collinearity between the VA of the two eyes. The lack of both formal model fit statistics from the GEE approach and theoretical knowledge to support the superiority of one model over another make it difficult to select the best model. CONCLUSION: Limitations of this analysis arise from the potential influence of collinearity between the VA of both eyes, and the use of contact lenses to reflect VA states to obtain the original dataset. Whilst further research is required to elicit more accurate utility values for wet AMD, this novel regression analysis provides a possible source of utility values to allow future economic models to capture the quality of life impact of changes in VA in both eyes. FUNDING: Novartis Pharmaceuticals UK Limited.

Cost-effectiveness of tolvaptan for the treatment of hyponatraemia secondary to syndrome of inappropriate antidiuretic hormone secretion in Sweden.

BACKGROUND: Tolvaptan is the only vasopressin V2 receptor antagonist licensed by the European Medicines Agency for the treatment of hyponatraemia (HN) secondary to the syndrome of inappropriate antidiuretic hormone secretion (SIADH). We have investigated the cost-effectiveness of tolvaptan versus no active treatment (NAT) in adult patients within the licensed indication who have either failed to respond to fluid restriction or for whom the use of fluid restriction is not suitable, from the societal perspective in Sweden. METHODS: A cost-utility analysis, considering a 'general SIADH' population and two subpopulations of patients (small-cell lung cancer [SCLC] and pneumonia) to broadly represent the complex clinical pathway of SIADH, was performed. A discrete event simulation was developed to model the progression of individuals through inpatient admissions over a 30-day time horizon (180 days for the SCLC cohort). Clinical data were derived from tolvaptan trials and observational data sources. All costs are given in Swedish kronor (SEK). RESULTS: In the 'general SIADH' population, tolvaptan was associated with reduced costs (SEK 5,779 per patient [€624]) and increased quality-adjusted life-years (QALYs) (0.0019) compared with NAT and was therefore the dominant treatment strategy. Tolvaptan was also associated with reduced costs and increased QALYs in the SCLC and pneumonia subpopulations. The most influential variables in our analysis were reduction in hospital length of stay, duration of treatment and long term treatment with tolvaptan in SCLC patients. CONCLUSIONS: Tolvaptan represents a cost-effective treatment option in Sweden for hospitalised patients with HN secondary to SIADH who have either failed to respond to or are unsuitable for fluid restriction.

Cost-Utility Analysis of Lurasidone Versus Aripiprazole in Adults with Schizophrenia.

BACKGROUND: In 2014, lurasidone, an atypical antipsychotic, was approved for the treatment of schizophrenia in adults. It is an alternative treatment option to aripiprazole, and when compared with aripiprazole, lurasidone was associated with improved symptom reduction and reduced risk of weight gain and relapse. We conducted a cost-utility analysis of lurasidone versus aripiprazole from the perspective of healthcare services, using Scotland and Wales as specific case studies. METHODS: A 10-year Markov model, incorporating a 6-week acute phase and a maintenance phase across three health states (discontinuation, relapse, death) was constructed. Six-week probabilities of discontinuation and adverse events were based on a published independent mixed-treatment comparison; long-term risks of relapse and discontinuation were from an indirect comparison. Costs included drug therapy, relapse, and outpatient, primary and residential care. Costs and benefits were discounted at 3.5 %. Utility estimates were taken from published literature, and cost effectiveness was expressed as total 10-year incremental costs and quality-adjusted life-years (QALYs). RESULTS: Lurasidone yielded a cost saving of £3383 and an improvement of 0.005 QALYs versus aripiprazole, in Scotland. Deterministic sensitivity analysis demonstrated that results were sensitive to relapse rates, while probabilistic sensitivity analysis suggested that lurasidone had the highest expected net benefit at willingness-to-pay thresholds of £20,000-30,000 per QALY. The probability that lurasidone was a cost-effective treatment strategy was approximately 75 % at all willingness-to-pay thresholds, with similar results being obtained for the Welsh analysis. CONCLUSIONS: Our analysis suggests that lurasidone would provide an effective, cost-saving alternative for the healthcare service in the treatment of adult patients with schizophrenia.

Cost-Effectiveness of Capsaicin 8% Patch Compared with Pregabalin for the Treatment of Patients with Peripheral Neuropathic Pain in Scotland.

We evaluated the cost-effectiveness of capsaicin 8% patch (QUTENZA™) versus pregabalin in patients with PNP from the perspective of the National Health Service (NHS) and Personal and Social Services in Scotland, UK. A decision-tree cost-effectiveness model was developed for non-diabetic patients with peripheral neuropathic pain (PNP) who were pregabalin-naïve and had not achieved adequate pain relief or tolerated conventional first- or second-line treatments. Patients entering the model received either a single application of capsaicin 8% patch or titrated daily dosing with pregabalin; after 8 weeks patients were classified as responders, non-responders, or were assumed to discontinue treatment due to intolerable adverse events. Responders continued to receive baseline treatment at intervals observed in clinical practice. Non-responders and those who discontinued treatment were assumed to receive last-line therapy (duloxetine). The base-case time horizon was 2 years. Model inputs for effectiveness, discontinuations and health-state utilities were taken from a head-to-head non-inferiority study (ELEVATE, NCT01713426). Other inputs were obtained from published sources or clinical expert opinion. Costs were expressed in GBP 2013/14. Results were presented as incremental cost-effectiveness ratios (ICER), i.e. cost per quality-adjusted life-year (QALY) gained. Model assumptions were tested with scenario analyses. Parameter uncertainty was tested using one-way and probabilistic sensitivity analyses. Compared with dose-optimized pregabalin, capsaicin 8% patch was the dominant treatment strategy (total cost difference, -£11; total QALY gain, 0.049). Capsaicin 8% patch was also the dominant treatment strategy versus pregabalin in 6 out of 7 scenario analyses. The model was most sensitive to variation in time to capsaicin 8% patch retreatment (maximum ICER, £7,951/QALY at lower-bound 95% confidence interval). At a willingness-to-pay threshold of £20,000/QALY, the probability of capsaicin 8% patch being cost-effective versus pregabalin was 97%. Capsaicin 8% patch is a cost-effective treatment option compared with dose-optimized pregabalin in patients with PNP who have failed one or more previous systemic treatments.

Inhaled aztreonam lysine versus inhaled tobramycin in cystic fibrosis. An economic evaluation.

RATIONALE: Pseudomonas aeruginosa infection is a significant cause of morbidity and mortality in patients with cystic fibrosis and is associated with a high economic burden. A recently published comparator trial demonstrated that outcomes in patients with cystic fibrosis with chronic P. aeruginosa infections switched from tobramycin solution for inhalation to aztreonam lysine for inhalation were better than those of patients who continued on tobramycin. OBJECTIVES: To compare overall costs of treatment of chronic inhaled tobramycin and aztreonam lysine in patient with cystic fibrosis who have chronic Pseudomonas infection, taking differences in outcomes into account. METHODS: A cost-effectiveness analysis with a 3-year time horizon was performed to simulate the economic consequences of either treatment from the perspective of a third party payer in the United States. We extrapolated results from the comparator trial and used data regarding clinical outcomes, quality of life, and costs from published literature and proprietary databases. A Markov structure was used to consider transitions between health states, defined principally by levels of percent predicted of FEV1. Extensive scenario and probabilistic sensitivity analyses were performed. MEASUREMENTS AND MAIN RESULTS: Use of aztreonam lysine for inhalation was associated with an average cost saving of $41,947 per patient over 3 years, as well as greater quality-adjusted life-years and total life-years. Scenario analyses demonstrated that these findings were robust to changes in key assumptions. CONCLUSIONS: It appears, with high likelihood, that the use of aztreonam solution for inhalation is associated with cost savings, an increase in quality-adjusted life-years, and improved clinical outcomes among patients with extensive prior use of tobramycin solution for inhalation who are naive to inhaled aztreonam lysine.

Will the Supreme Court finally eliminate ERISA preemption?

David Trueman's article reviews the history of ERISA preemption by analyzing seminal Supreme Court cases and predicts the future of ERISA preemption in his analysis of recent federal case law. Traditionally, the ability to hold a managed care entity responsible for its actions has been hampered by a strict interpretation of the preemption clauses of ERISA but as the Supreme Court's jurisprudence has evolved and loosened, several federal courts have allowed suits against managed care companies to go forward. Conflict among the federal circuits has arisen and the Supreme Court has granted certiorari to two cases from Texas in order to clarify ERISA preemption. Mr. Trueman discusses the future of ERISA preemption in light of these decisions.

The impact of the recent Supreme Court rulings in Pegram and Rush Prudential on state regulation of managed care organizations.

Over the past two decades, the Employee Retirement Income Security Act of 1974 (ERISA) has shielded managed care organizations (MCOs) from liability for negligent treatment or coverage decisions. This Article examines the Supreme Court jurisprudence in the area of ERISA preemption, and assesses the impact of these recent decisions on state regulation of MCOs. The author concludes that recent decisions in Pegram v. Herdrich and Rush Prudential HMO, Inc. v. Moran have broadened the states' power to regulate MCOs and enhance the ability of injured plaintiffs to sue such organizations under state tort law.

The liability of medical directors for utilization review decisions.

Managed Care Organizations (MCOs) have turned to numerous cost-containment measures to combat rising healthcare costs. One of the most common is the use of utilization review to ascertain whether a recommended mode of treatment is "medically necessary." When the medical director of an MCO determines that care recommended by a patient's treating physician is not medically necessary and not eligible for coverage (and, as a result, potentially unattainable due to cost), the stage is set for litigation. In such situations, medical directors may become potentially liable for disciplinary action by their state medical licensing board as well as lawsuits for malpractice or negligence. However, plaintiffs wishing to recover damages for improper determinations of this nature or state boards trying to discipline these physicians, face the hurdles of the preemptive force of ERISA, and state doctrines to the effect that corporations (and, derivatively, their medical directors) cannot practice medicine and therefore cannot be liable for malpractice. Conflicting decisions and opinions make it impossible at the present time to have a settled expectation regarding the potential liability of medical directors in this context, although the law appears to be moving toward the treatment of utilization review as medical decisionmaking; therefore, it appears likely that the activities of medical directors increasingly will face state oversight--including the imposition of common law liability in appropriate situations.