Cost-effectiveness analysis of mechanical thrombectomy with stent retriever in the treatment of acute ischemic stroke in Italy

Background: Stroke has a significant disease burden in terms of acute and long-term disability in Italy and throughout the world. Endovascular treatments for the management of a stroke event have been coupled in the past years with the possibility to mechanically remove the occlusion by means of specially designed thrombectomy devices, and their exclusive use showed levels of effectiveness in line with those of the existing pharmacological treatments.

Objective: To assess the cost-effectiveness of mechanical thrombectomy (MT) with the Solitaire Revascularization Device (stent retriever) for the treatment of acute ischemic stroke (AIS) in patients with large vessel occlusions (LVOs), comparing MT plus intravenous tissue plasminogen activation (MT plus IV t-PA) vs IV t-PA alone, in Italy.

Methods: A Markov model was used to simulate costs and benefits of MT plus IV t-PA and IV t-PA alone over a 5-year time horizon and considering the perspective of the Italian National Health Service (NHS). Results are reported in terms of Incremental Cost Effectiveness Ratio (ICER). Deterministic and probabilistic sensitivity analyses are carried out in order to test the robustness of the results.

Results: Total costs of MT plus IV t-PA and IV t-PA alone are equal to €31,798 and €34,855, respectively. The MT allows incremental QALYs for 0.77, determining a dominant ICER. The utilities associated to the mRS health states are the parameters with the highest impact on the results. Multiway sensitivity analyses determined a 90% probability of dominance.

Conclusions: MT plus IV t-PA for AIS patients with LVO is cost-effective from year 1 through year 3, and cost-saving from year 4 onward in the Italian context, achieving better results, both in terms of efficacy and in terms of resource consumption.     

Subcutaneous vs intravenous rituximab in patients with non-Hodgkin lymphoma: a time and motion study in the United Kingdom

Objective:

Rituximab is part of standard therapy for many non-Hodgkin lymphoma (NHL) patients, and is usually administered as an intravenous (IV) infusion. A formulation for subcutaneous (SC) injection will be available from June 2014. A time and motion study was conducted to investigate the staff time and costs associated with administration of SC and IV rituximab.

Research design and methods:

The time and motion study was conducted in three UK centers alongside a phase III trial of SC rituximab in patients with NHL (ClinicalTrials.gov identifier NCT01461928). Active healthcare professional (HCP) time spent on the preparation and administration of IV and SC rituximab was recorded and used to calculate the associated costs.

Results:

Total active HCP time associated with administration of IV rituximab was 223.3?min (95% CI?=?218.0–228.7), vs 48.5?min (95% CI?=?45.5–51.6) for SC rituximab, a saving of 174.8?min (95% CI?=?172.5–177.1) per session. Patient time in the treatment room was 263.8?min (95% CI?=?236.6–294.3) for IV rituximab and 70.0?min (95% CI?=?57.1–87.2) for SC rituximab, per session. The SC formulation reduced total mean staff costs by £115.17 (95% CI?=?98.95–136.93) per session. Differing monitoring scenarios during infusion consistently showed time and cost savings for SC rituximab.

Limitations:

Study limitations include the non-interventional design and lack of statistical power, and the investigational nature of SC rituximab. The data collected did not account for patient and center characteristics and variability on active HCP time.

Conclusions:

SC rituximab was associated with reduced active HCP time and costs vs IV rituximab, as well as reduced patient time in the treatment room. Switching from IV to SC rituximab could increase treatment room capacity and patient throughput, as well as improving the patient experience.     

Managing acute acetaminophen poisoning with oral versus intravenous N-acetylcysteine: a provider-perspective cost analysis

Abstract

Background: Acetaminophen (APAP) overdose, which can lead to hepatotoxicity, is the most commonly reported poisoning in the United States and has the highest rate of mortality, with more than 100,000 exposures and 300 deaths reported annually. The treatment of choice, N-acetylcysteine (NAC), is effective in both oral (PO) and intravenous (IV) formulations. The main difference in therapies, other than administration route, is time to complete delivery – 72 hours for PO NAC versus 21 hours for IV NAC, according to full prescribing information. This distinction is the primary basis for variation in management costs for hospitalized patients receiving these products.

Objectives: To quantify and compare full treatment costs from the provider perspective to manage acute APAP poisoning with either PO or IV NAC in a standard treatment regimen.

Methods: A cost model was developed and populated with published data comprising probabilities of potential clinical outcomes and the costs of resources consumed during patient care.

Results: For patients who present <10 hours post-ingestion, the estimated total cost of care with PO NAC in the treatment regimen is $5,817 (ICU patients) or $3,850, (ward patients) compared with $3,765 and $2,768 for similar care with IV NAC. Potential cost savings equal – $2,052 (–35%) or –$1,083 (–28%), respectively, in favor of IV NAC. Similar potential savings were estimated for patients presenting 10–24 hours post-ingestion.

Conclusion: IV NAC is the less costly therapeutic option for APAP poisonings, based on simulation modeling and retrospective data. The current economic evaluation is restricted by the absence of comparative data from head-to-head, matched-cohort studies and the limitations common to retrospective APAP toxicology datasets. Additional research could refine these results.     

A multidimensional spatial lag panel data model with spatial moving average nested random effects errors

This paper focuses on a three-dimensional model that combines two different types of spatial interaction effects, i.e. endogenous interaction effects via a spatial lag on the dependent variable and interaction effects among the disturbances via a spatial moving average (SMA) nested random effects errors. A three-stage procedure is proposed to estimate the parameters. In a first stage, the spatial lag panel data model is estimated using an instrumental variable (IV) estimator. In a second stage, a generalized moments (GM) approach is developed to estimate the SMA parameter and the variance components of the disturbance process using IV residuals from the first stage. In a third stage, to purge the equation of the specific structure of the disturbances a Cochrane–Orcutt-type transformation is applied combined with the IV principle. This leads to the GM spatial IV estimator and the regression parameter estimates. Monte Carlo simulations show that our estimators are not very different in terms of root mean square error from those produced by maximum likelihood. The approach is applied to European Union regional employment data for regions nested within countries.     

Lower and upper bounds of returns to schooling: An exercise in IV estimation with different instruments

Several recent studies based on `exogenous' sources of variation in educational outcomes show IV estimates of returns to schooling that are substantially higher than the corresponding OLS estimates. Card (1995a, Earnings, schooling, and ability revisited. Research in Labor Economics 14, 23–48) suggests that these results are explained by the existence of heterogenity in individual returns and by the fact that these studies are based on instruments that influence only the educational decision of individuals with high marginal returns due to either liquidity constraints or to high ability. This conclusion is consistent with the local average treatment effect (LATE) interpretation of IV (Imbens and Angrist (1994, Identification and estimation of local average treatment effects. Econometrica 62, 467–475) according to which IV identifies only the average returns of those who comply with the assignment-to-treatment mechanism implied by the instrument. We show evidence for Germany suggesting that returns to schooling are heterogeneous, instruments matter and the LATE interpretation of IV makes sense. With an appropriate choice of instruments we also show how IV can be used to approximate the range of variations of returns to schooling in Germany.     

Updated trends in US brand-name and generic drug competition

Objective: To provide updated evidence on US trends in: market exclusivity periods (MEPs, time between brand-name drug launch and first generic competitors) for new molecular entities (NMEs); likelihood, timing and number of Hatch-Waxman Act Paragraph IV patent challenges; and generic drug penetration.

Methods: This study used IMS Health National Sales Perspectives^TM US data to calculate MEPs for the 288 NMEs experiencing initial generic entry between January 1995 and December 2014, the number of generic competitors for 12 months afterward (by level of annual sales prior to generic entry), and generic penetration rates. The likelihood, timing and number of Paragraph IV challengers were calculated using data from Abbreviated New Drug Approval (ANDA) letters, the FDA website, public information searches, and ParagraphFour.com.

Results: For drugs experiencing initial generic entry in 2013–2014, the MEP was 12.5 years for drugs with sales greater than $250 million (in 2008 dollars) in the year prior to generic entry ($250 million?+?NMEs), 13.6 years overall. After generic entry, brands rapidly lost sales, with their average unit share being 7% at 1 year for $250 million?+?NMEs, 12% overall. Ninety-four percent of $250 million?+?NMEs experiencing initial generic entry in 2013–2014 had faced at least one Paragraph IV challenge, an average of 5.2 years after brand launch (76% and 5.9 years for all NMEs). NMEs faced an average of 5.1 and 6.2 Paragraph IV challenges per NME, for all and $250 million?+?NMEs, respectively.

Limitations: Analyses, including Paragraph IV calculations, were restricted to NMEs where generic entry had occurred.

Conclusion: The average 2013–2014 MEP of 12.5 years for $250 million?+?NMEs, 13.6 overall remains consistent with prior research. MEPs are lower, and Paragraph IV challenges are more frequent and occur earlier for $250 million?+?drugs. Generic share erosion is also greater, and continues to intensify for both NME types.     

Let the Data Speak? On the Importance of Theory‐Based Instrumental Variable Estimations

In absence of randomized‐controlled experiments, identification is often aimed via instrumental variable (IV) strategies, typically two‐stage least squares estimations. According to Bayes’ rule, however, under a low ex ante probability that a hypothesis is true (e.g. that an excluded instrument is partially correlated with an endogenous regressor), the interpretation of the estimation results may be fundamentally flawed. This paper argues that rigorous theoretical reasoning is key to design credible identification strategies, the foremost, finding candidates for valid instruments. We discuss prominent IV analyses from the macro‐development literature to illustrate the potential benefit of structurally derived IV approaches.     

Pharmacological control of secondary hyperparathyroidism in hemodialysis subjects: a cost consequences analysis of data from the FARO study

Abstract

Background and objectives:

Secondary hyperparathyroidism (SHPT) is a frequent complication of CKD with incidence, prevalence, and costs increasing worldwide. The objective of this analysis was to estimate therapy cost of SHPT in a sub-population of the FARO study.

Materials and Methods:

In the FARO study, an observational survey aimed to evaluate patterns of treatment in patients with SHPT who had undergone hemodialysis, pharmacological treatments and biochemical parameters evolution data were collected in four surveys. Patients maintaining the same treatment in all sessions were grouped by type of treatment and evaluated for costs from the Italian National Health Service perspective.

Results:

Four cohorts were identified: patients treated with oral (PO) calcitriol (n?=?182), intravenous (IV) calcitriol (n?=?34), IV paricalcitol (n?=?62), and IV paricalcitol?+?cinacalcet therapy (n?=?20); the cinacalcet monotherapy group was not analysed due to low number of patients (n?=?9). Parathyroid hormone (PTH) level at baseline and effectiveness of treatments in suppressing PTH level were assessed to test comparability among cohorts: calcitriol PO patients were significantly less severe than others (PTH level at baseline lower than 300?pg/ml; p?<?0.0001); calcitriol IV patients did not reach significant reduction in PTH level. Paricalcitol and paricalcitol?+?cinacalcet treatment groups results were comparable, while only the IV paricalcitol cohort’s PTH level, weekly dosage, and cost decreased significantly from the first to the fourth survey (p?=?0.020, p?=?0.012, and p?=?0.0124, respectively). Total costs per week of treatment (including calcium-based phosphate binder and sevelamer) were significantly lower in the paricalcitol vs paricalcitol?+?cinacalcet cohort (p?<?0.001). Major limitations of this study are related to the survey design: not controlled and lack of comparability between cohorts; however, reflective of true practice patterns.

Conclusions:

The IV Paricalcitol cohort had significantly lower treatment costs compared with patients treated with paricalcitol?+?calcimemtics (p?<?0.001), without a significant difference in terms of baseline severity and PTH control.     

Forecasting Canadian consumption using the Dynamic Generalized Linear Expenditure System (DGLES)

This paper uses the Dynamic Generalized Linear Expenditure System (Dgles) to: 1. study the behaviour of the Canadian consumer; and 2. provide ex postforecasts of consumption expenditures by commodity group. The model is estimated for seven commodity groups (durables, food, fuel, gasoline, other non-durables, semi-durables and services) using quarterly data covering the period 1961.I–1978.IV. The method of estimation is the full information maximum likelihood routine, and the ex postforecasts are provided for the period 1979.I–1981.IV.     

Dollars and pounds: the impact of family income on childhood weight

This article examines the impact of family income on childhood weight status for children in the United States using matched mother-child data from the National Longitudinal Survey of Youth (NLSY 79). Instrumental variable (IV) models, family Fixed Effects (FE) models and family Fixed Effects IV (FEIV) models are estimated in order to control for causality. The results suggest that although the prevalence of childhood obesity is higher in low-income families in the sample, family income might be acting primarily as a proxy for other unobserved characteristics that determine the child's weight status rather having a major direct causative role in determining the child's weight status.     

The quality of consumption: Some Australian evidence

The paper reports new estimates of Theil's index of the quality of consumption for four age groups and at two levels of affluence (income) for Australian households over the period 1975.IV to 1982.IV with special emphasis on the role played by energy and non-energy commodity groups. The evidence reveals an improvement in the quality of consumption of energy and energy-related goods and a quality deterioration in food, clothing and rent at all income levels and for all four age groups.     

Persistence, Asymmetries and Interrelation in Factor Demand

A neoclassical factor demand model for structures, equipment and labour is analyzed in this paper. It incorporates a variety of dynamic specifications, such as a multi-period time-to-build for structures, internal adjustment costs for each production factor, and external investment adjustment costs. First-order conditions of the model are estimated by the generalized method of moments using manufacturing industry data from the US, Canada, West Germany, the UK (all 1960.I–1988.IV), France (1970.I–1992.II) and the Netherlands (1971.I–1990.IV). The results endorse time-to-build for structures, persistence of technology shocks and interrelations in adjustment cost dynamics.     

Development and validation of a new instrument to evaluate the ease of use of patient-controlled analgesic modalities for postoperative patients

Abstract

Objective: To describe the development and psychometric evaluation of a questionnaire assessing the ease of use that patients associate with patient-controlled analgesia (PCA) modalities.

Methods: Qualitative interviews were conducted with patients who had experience with intravenous (IV) PCA for postoperative pain management to generate items relevant to the ease of using PCA modalities. The content validity of the resulting questionnaire was examined through follow-up patient interviews, and an expert panel reviewed the questionnaire. Cognitive debriefing interviews were conducted with patients to determine the clarity and content of the instructions, items, and response scales, and the ease of completing the instrument. Psychometric evaluation was performed with patients who had undergone surgery and received IV PCA for postoperative pain management. Item and scale quality and the internal consistency reliability of the questionnaire were assessed. Construct validity was evaluated by examining the relationship between subscales of the questionnaire with patient-reported outcome measures. Known-groups validity was determined by assessing the instrument's ability to differentiate between patients with versus without an IV PCA problem. A potential limitation of this study was the exclusive sampling of patients who had experience with IV PCA.

Results: The Patient Ease-of-Care (EOC) Questionnaire included 23 items in the following subscales: Confidence with Device, Comfort with Device, Movement, Dosing Confidence, Pain Control, Knowledge/Understanding, and Satisfaction. Coefficient alpha reliability estimates were ≥0.66 for Overall EOC (includes all subscales except Satisfaction) and all EOC subscales. Construct validity was supported by the moderate relationship between the Pain Control subscale and measures of pain severity and pain interference; additional evidence of construct validity was provided by correlations of the Confidence with Device subscale, the Satisfaction subscale, and Overall EOC with measures of pain severity, pain interference, and satisfaction. Significant mean score differences were reported between participants with and without IV PCA problems for Overall EOC and for the Comfort with Device, Confidence with Device, Movement, Pain Control, and Satisfaction subscales indicating known-groups validity.

Conclusions: Results provide evidence for the reliability and validity of the Patient EOC Questionnaire as a measure of the ease of use that patients associate with PCA systems and may be useful for evaluating emerging PCA modalities.     

EMPLOYMENT EFFECTS OF THE MINIMUM WAGE: PANEL DATA EVIDENCE FROM CANADIAN PROVINCES

Recent U.S. studies offer conflicting evidence on minimum wage impacts. This paper studies the effects of 185 amendments to minimum wage on employment rates using panel data across Canadian provinces from 1981 to 2011. Ordinary least squares and instrumental variables (IV) estimates imply a 10% increase in minimum wage is associated with a 1%–4% reduction to employment rates for both male and female teens. We also find that an increase in the minimum wage is associated with lower employment of prime‐aged immigrants. Our results are robust to a wide array of IV and the use of controls for spatial heterogeneity. (JEL J30, J71, J23)     

Consumption,co-integration and varying coefficients: the Australian evidence

An aggregate consumption function incorporating random coefficient approach is estimated to investigate the changing pattern of consumer response in Austrialia using quarterly data from 1959: IV to 1990: IV. The methdology applied is that of Hidreth and Houck (1968), Singh et al. (1976) and Hoque (1991). The largenge multiplier test, as suggested by Breush and Pagan (1979), supports the hypothesis of randomness in the response coefficients. Our Study indicates strong dependence on the first-difference of income and that consumers respond quite slowly to short-run fluctuations. This is because consumption and income have been found to be integrated of order one and co-integrated. Thus, as error correction model has been estimated following Engle and Granger (1987).     

Structure of research on biomass and bio-fuels: A citation-based approach

Biomass and bio-fuels have gained a growing interest as sustainable and renewable energy. In this paper, we perform a citation network analysis of scientific publications to know the current structure of biomass and bio-fuel research. By clustering and visualizing the network, we revealed their taxonomic structure. Emerging technologies are detected by analyzing the average publication year of clusters. According to the results, bio-diesel and hydrogen production are the most rapidly developing domains among biomass bio-fuel researches. We also analyzed the position of each cluster in the global structure of research. By using citation counts within and out of the cluster, we categorized each cluster into the following four categories: (I) topic specific; (II) domain specific; (III) global link; and (IV) specific & global. For research domains of category (III) or (IV), it is difficult that single technology overcomes the current limitation of bio-energy productions. Research on lignocellulose feedstock is a typical case where knowledge from other scientific disciplines is necessary.     

Economic assessment of doripenem versus imipenem in the treatment of ventilator-associated pneumonia

Abstract

Background: Ventilator-associated pneumonia (VAP), the most common nosocomial infection in critically ill patients, is associated with significantly longer duration of mechanical ventilation, and increased mortality, hospital days, and health-care costs. A previously published prospective, randomized study established the noninferiority of intravenous (IV) doripenem versus IV imipenem/cilastatin (‘imipenem‘) for VAP. This study compares the economic outcomes of IV therapy with doripenem versus imipenem as first-line treatment for VAP.

Methods: A decision-analytic model of inpatient care and outcomes for VAP was used to estimate costs associated with VAP treatment. The model calculates total hospital costs, comprising costs of initial and concomitant therapy, and costs associated with mechanical ventilation, intensive care unit stays, and total days in hospital.

Results: Total treatment costs for doripenem were $10,630 lower than for imipenem ($71,259 vs. 81,889), driven primarily by differences in costs of mechanical ventilation ($45,224 for doripenem, $57,348 for imipenem). Probabilistic sensitivity analyses found doripenem consistently cost saving versus imipenem in 1,000 simulations. Study limitations include use of a simple model to represent a complex disease process and reliance on trial data that may not reflect real-world care and outcomes.

Conclusions: Doripenem is a cost saving first-line treatment for VAP versus imipenem while providing an equivalent rate of cure.     

THE SO2 EMISSIONS TRADING PROGRAM: COST SAVINGS WITHOUT ALLOWANCE TRADES

Title IV of the 1990 amendments to the Clean Air Act initiated a historic experiment in incentive-based environmental regulation by permitting electric generating facilities to trade allowances for emission of sulfur dioxide. To date, relatively little allowance trading has occurred. However, the costs of compliance have been much less than anticipated. The purpose of this paper is to address the apparent paradox—that the allowance trading program may not require (very much) trading in order to be successful. Title IV represented two great steps forward in environmental regulation: (i) a move toward performance standards and (ii) formal allowance trading. The first step has been sufficient to date for improving dynamic efficiency and achieving relative cost-effectiveness.     

Social Interaction Effects in Disability Pension Participation: Evidence from Plant Downsizing*

We estimate the magnitude of social interaction effects in disability pension participation among older workers in Norway. The problem of omitted variable bias is addressed using the exposure of an individual's neighbors to plant‐downsizing events as an instrument for the disability entry rate among the individual's previously employed neighbors. Our instrumental variable (IV) estimates suggest that an increase of one percentage point in the participation rate of previously employed neighbors increased the subsequent four‐year entry rate of older workers by about 0.4 percentage points. Numerous robustness and specification tests appear to support the validity of the identifying assumption in our IV strategy.     

The inflation rates may accelerate after all: panel evidence from 19 OECD economies

The stationarity of inflation has many important economic implications. Most panel-based empirical studies do not handle cross-sectional dependence, which will result in power distortion. This paper applies a nonlinear IV estimator to calculate the test statistic of panel unit root (Chang in J Econom 110:261–292, 2002), which accounts for general cross-sectional correlation. Using monthly inflation rates, two statistics proposed by Im et al. (J Econom 115:53–74, 2003) reject the unit root; however, the nonlinear IV statistic accepts the unit root. That is, the ignored cross-sectional correlation may lead to over-rejection of the unit root null. In a nutshell, unlike current literature, the inflation rates may accelerate after all.