Orietta Zaniolo

Effectiveness and cost-effectiveness of supplemental glutamine dipeptide in total parenteral nutrition therapy for critically ill patients: a discrete event simulation model based on Italian data.

INTRODUCTION The supplementation of alanyl-glutamine dipeptide in critically ill patients necessitating total parenteral nutrition (TPN) improves clinical outcomes, reducing mortality, infection rate, and shortening intensive care unit (ICU) hospital lengths of stay (LOSs), as compared to standard TPN regimens. METHODS A Discrete Event Simulation model that incorporates outcomes rates from 200 Italian ICUs for over 60,000 patients, alanyl-glutamine dipeptide efficacy data synthesized by means of a Bayesian random effects meta-analysis, and national cost data has been developed to evaluate the alternatives from the cost perspective of the hospital. Simulated clinical outcomes are death and infection rates in ICU, death rate in general ward, and hospital LOSs. Sensitivity analyses are performed by varying all uncertain parameter values in a plausible range. RESULTS The internal validation process confirmed the accuracy of the model in replicating observed clinical data. Alanyl-glutamine dipeptide on average results more effective and less costly than standard TPN: reduced mortality rate (24.6% ± 1.6% vs. 34.5% ± 2.1%), infection rate (13.8% ± 2.9% vs. 18.8% ± 3.9%), and hospital LOS (24.9 ± 0.3 vs. 26.0 ± 0.3 days) come at a lower total cost per patient (23,409 ± 3,345 vs. 24,161 ± 3,523 Euro).Treatment cost is completely offset by savings on ICU and antibiotic costs. Sensitivity analyses confirmed the robustness of these results. CONCLUSIONS Alanyl-glutamine dipeptide is expected to improve clinical outcomes and to do so with a concurrent saving for the Italian hospital.

The cost effectiveness and cost utility of valsartan in chronic heart failure therapy in Italy: a probabilistic markov model.

ObjectiveTo evaluate the cost effectiveness and cost utility of the use of valsartan in addition to standard therapy for the treatment of patients with chronic heart failure with low left ventricular ejection fraction (LVEF).MethodsThe study was conducted by means of a cohort simulation based on a probabilistic Markov model and projecting the 23-month follow-up results of the Val-HeFT (Valsartan Heart Failure Trial) study over a 10-year time horizon. The model included four states (New York Heart Association [NYHA] classes II, III, IV, and death), and had a cycle duration of 1 month. Probabilistic simulations were performed using the WinBUGS software for Bayesian analysis. The distribution of patient parameters (sex, age, use of β-adrenoceptor antagonists, and ACE inhibitors) in the simulated population were derived from the Italian heart failure patient population. Individual mortality data were derived from general mortality data by multiplying by a NYHA state-specific relative risk, while the probability of changing NYHA class was taken from the Val-HeFT data. Costs (2007 values) were calculated from the perspective of the Italian Health Service (IHS) and included costs for drugs and heart failure hospitalizations. Quality-of-life (QOL) weights were obtained byusing published health-related QOL data for heart failure patients.A 3.5% annual discount rate was applied. Probabilistic sensitivity analysis was performed on each parameter using original-source 95% confidence interval (CI) values, or a ±10% range when 95% CI values were unavailable.ResultsFor the 10-year time horizon, patients were estimated to live for an average of 2.3 years or 1.7 quality-adjusted life-years (QALYs), with slight increases in the valsartan group. In this group, hospitalizations for worsening heart failure were predicted to be significantly reduced and overall treatment costs per patient to decrease by about €550. In subgroup analyses, valsartan lost dominance in patients in NYHA II, and in those receiving β-adrenoceptor antagonists or ACE inhibitors; the mean incremental cost-utility ratio for these groups was 21 240, 129 200, and 36 500 €/QALY, respectively.ConclusionsValsartan in addition to standard therapy is predicted to dominate standard therapy alone in Italian patients with mild to severe heart failure and low LVEF. There are relevant differences among various patient subgroups, and valsartan is expected to be good value for money particularly in the treatment of the most severe and less intensively treated (no ACE inhibitors, no β-adrenoceptor antagonist) heart failure patients.

Cost-effectiveness of blood culture and a multiplex real- time PCR in hematological patients with suspected sepsis: an observational propensity score-matched study

We evaluated the costs and clinical outcomes of episodes of suspected sepsis in hematological patients. A propensity score-matched study was planned, comparing a retrospective cohort managed with standard assays and a prospective cohort managed with the addition of a molecular assay. Diagnostic procedures and therapy were considered as costs variables. The primary clinical endpoint was sepsis-related mortality, whereas the length of each suspected sepsis episode was investigated as a secondary endpoint. A total of 137 and 138 episodes in the prospective and the retrospective cohorts were studied, respectively; 101 pairs of highly matched episodes were analyzed, evidencing a trend of higher mortality in the retrospective cohort. No difference in length of suspected sepsis episode was observed. Significant savings were observed in the prospective cohort, especially due to reduced costs in antifungal therapy. The apparently more expensive molecular assay favored a more rational use of economic resources without influencing, and probably improving, the clinical outcome.

Plasma for fractionation in a public setting: cost analysis from the perspective of the third-party payer

BACKGROUND In Italy, within the legal mandate to pursue national self-sufficiency of plasma-derived medical products, the Regions are starting to organise trade to offset imbalances between need and availability. It is, therefore, necessary to determine the full cost to the Regions of plasma collection and handling. Here we report an analysis of plasma production costs in the Department of Transfusion Medicine of Verona Province, Veneto Region. MATERIALS AND METHODS Plasma is obtained from voluntary, non-remunerated donors from either whole blood or apheresis donation, and in Verona it is collected, validated and distributed only in Regional Health Service facilities, and then delivered to industry for processing. The amounts and costs of materials and activities needed to collect, produce, validate and distribute plasma were obtained from the Department of Transfusion Medicine. Attributable overhead expenses were assumed at 15% of direct costs. When plasma was collected as part of whole blood or from multi-component apheresis, joint costs (the costs of the common manufacturing process before the separation) were allocated to the plasma based on the tariff for single components, taken as proxy of the willingness to pay for them. In an alternative scenario plasma recovered from whole blood donations was considered a by-product. RESULTS The estimated full cost of each valid unit of plasma derived from whole blood, multi-component apheresis, and plasma-apheresis was about € 30, € 73 and € 170, respectively. The estimated total cost per litre of plasma was € 113 for collection from whole blood and € 276 for collection from apheresis. When plasma recovered from whole blood donations was considered a by-product, its cost per litre was estimated to be € 26. DISCUSSION Our results suggest that the Italian donor-based system, in addition to its ethical and social values, can supply plasma at an affordable cost, comparable (albeit slightly higher) with costs in other recent analyses.

Tiotropium bromide in the routine care of GOLD stage II COPD patients: a pharmaeconomic evaluation

Background: a secondary pre-specified analysis of the UPLIFT cohort demonstrated that the inclusion of tiotropium bromide in the routine care of GOLD stage II (moderate) chronic obstructive pulmonary disease (COPD) patients is associated with stronger improvements of survival, quality of life, and exacerbation rate than those shown in the total cohort; in this subgroup, tiotropium furthermore induces a significant reduction in the rate of FEV1 decline. Objective: to adapt the Spiriva® model, originally built to evaluate cost-effectiveness of tiotropium inclusion in the general COPD population, to GOLD II patients. Methods: the Spiriva® model is a probabilistic Markov patient-level simulation developed over a lifetime horizon to compare outcomes associated with the inclusion of tiotropium in routine care (RC) for COPD treatment with those obtained with RC alone. Patients are characterised by gender, age, height, smoking status and FEV1. Model structure and sources have been maintained unvaried, except for demographic characteristics, specific for GOLD II patients, as extrapolated from an Italian observational study, and tiotropium efficacy, based on the secondary analysis of GOLD II UPLIFT patients. As in the original model, only direct health care costs are considered. Results: patients treated with tiotropium on average (95% CI) gain 0.70 (0.00/7.23) LYs or 0.77 (0.02/4.67) QALYs compared to RC. The incremental lifetime cost is € 3,520 (-6,391/26,686), meaning that the incremental cost required to gain a QALY (incremental cost-effectiveness ratio – ICER) is equal to € 4,548. Sensitivity analysis shows that tiotropium has a 50% probability of being cost-effective for a willingness-to-pay (WTP) around 4,600 €/QALY; 100% probability is achieved with a WTP of € 9,300. Conclusions: the adoption of a strategy based on the inclusion of tiotropium from the early COPD stages represents good value for money in Italy, as the ICER estimated for GOLD II patients is well below conventional WTP thresholds, and lower than that calculated for the entire UPLIFT cohort.

Estimation of economic consequences of GOLD guidelines adoption in the Italian clinical practice

Background: Chronic Obstructive Pulmonary Disease (COPD) affects about 4.5% of the Italian population, representing one of most burdensome public health problems. Literature data report an annual health care expenditure ranging between € 1,300 and € 4,500 per patient, of which drug costs are a limited share. In 1998 the WHO started GOLD program in order to ameliorate COPD patient management. As a part of his program, periodically updated guidelines are produced with the aim of defining an efficient diagnostic-therapeutic pathway managed by a multidisciplinary team and based on the optimization of the use of drugs and diagnostic tests and the reduction of exposure to risk factors. Objective: to estimate the economic consequences of GOLD guidelines adoption in the Italian clinical practice. Methods: a decision analytic model capable of calculating the impact on the National Health Service budget of an ameliorated adherence to GOLD guidelines (GOLD GL strategy), basing on the needed variations in health care strategies on a defined patient cohort treated with the current approach (CURRENT strategy). The simulation runs on a cohort representing Italian COPD patients over 45 years who transit through 5 Markov health states (4 GOLD stages and death), according to patient characteristics (age, gender, FEV1), with a time horizon of 3 years. Stage-specific drug consumption of the CURRENT strategy is based on data of 3,113 patients collected by three Health Local Units involved in a larger clinical audit project. The consumption of other health resources, i.e. medical visits and inpatient care, is estimated based on a multicentre observational Italian study. The GOLD GL strategy includes spirometry-based staging on the totality of the simulated patients, the development of a therapeutic strategy including the redefinition of pharmacological therapy based on guideline recommendations and experts opinion, and variation of other health resources consumption based on observational data. Costs of health care resources are calculated based on published micro-costing analysis and current prices and tariffs. Results: the model estimates an adjunctive cost of about 19 million of Euros with the GOLD GL strategy, just for the the spirometry-based restaging of about 40% of the over 1 million and 250 thousand prevalent Italian COPD patients. Furthermore, in the first year of the analysis, the redefinition of the best clinical management strategy for all patients would cost about 100 million Euros, which are to be added to the more than 320 million Euros associated with adaptation of the GOLD stage specific pharmacological therapy, consisting mainly in a higher usage of long-acting beta agonist/corticosteroid combinations, only partially offset by the lower prescription of corticosteroid alone. Based on Italian observational data, the consumption of other health care resources with the GOLD GL strategy is reduced by about 44%, reflected in an estimated cost saving of more than 850 millions of Euros. For the first analysis year, the net cost saving associated with full GOLD guideline adoption is estimated equal to 410 millions of Euros; this value decreases by 11% and 21% respectively in the second and third years. Conclusion: our model estimates that the adoption of GOLD guidelines in the Italian clinical practice is associated to an average cost saving of about 300 Euros per patient/year.

Organization and estimated patient-borne costs of oral anticoagulation therapy in Italy: results from a survey.

BackgroundThe management of the large patient population in Italy receiving long-term oral anticoagulation therapy (OAT) poses organizational challenges that are traditionally approached with a centralized procedure, relying on hospital-based clinics and/or GPs. However, the availability of near-patient testing devices for the monitoring of OAT effectiveness (international normalized ratio measurement) allows for alternative or complementary management models, in which adequately trained patients perform the test themselves and possibly make decisions about dosing adjustments (patient self-monitoring). Patient self-monitoring has been proven to be effective and safe, and is economically attractive. However, in order to assess its potential economic impact in Italy, there is a need for data on current treatment patterns and relative costs, which are currently not available.ObjectiveTo establish prevalent management patterns and costs incurred by Italian OAT patients.MethodsAn ad hoc questionnaire was developed and administered to OAT patients with the support of the main Italian OAT patients association. Returned questionnaires were checked for consistency and valid data were summarized. Resources used were costed according to published prices.ResultsA total of 4722 valid questionnaires were returned from all over Italy. The prevalent OAT management model in this sample relied on hospital-based anticoagulation clinics. Significant earning losses, transportation costs and other out-of-pocket expenses were incurred by patients, with an estimated mean overall monthly cost of approximately €30 (year 2008 value). There was a wide distribution of costs in this population, depending mainly on monitoring frequency, home-to-clinic distance and employment status.ConclusionThis study contributes to clarifying the organizational models of the Italian OAT population and delivers data on treatment patterns and costs that may be used when planning and evaluating alternative management options.

Sartans: differences, similitudes and costs

The search for a more specific and complete blockade of the hypertensive effects of angiotensin and of better tolerability than ACE-inhibitors has led to the development of angiotensin II receptor blockers (ARBs), which were introduced about 10 years ago. During this period they have been evaluated in several large studies in terms of efficacy and safety in reducing blood pressure, as well as for cardiovascular and renal protection. In patients with heart failure, valsartan, candesartan and, partially, losartan have been shown to be associated with positive outcomes both as monotherapy, when ACE-inhibitors are contraindicated or not tolerated, and in combination with ACE-inhibitors standard therapy. Among ARBs, valsartan is the only that is also approved for treatment of patients with both heart failure and recent myocardial infarction. In light of the high costs related to cardiovascular disorders, agents that reduce cardiovascular risk, like ARBs, represent a potential long-term health cost saving strategy, if used according to guidelines in approved indications. Valsartan has a daily cost which is lower than the mean cost of the class. Furthermore, this drug shows one of the lowest costs for patient brought to blood pressure goals in its class. In this paper, economic evaluations conducted on the results of large trials were reviewed. Their results add economic rationale to the therapeutic algorithms recommended by clinical guidelines on heart failure management; using valsartan, or other evaluated ARBs, in heart failure patients who are intolerant or contraindicated to ACE-inhibitors therapy, is expected to be highly cost/effective. In combination with ACE-inhibitors in those patients not on beta-blocker therapy, its cost/effectiveness is somewhat worse, but still acceptable, with an estimated cost of 15,000 USDs for life year saved. In summary, when used for approved indications, valsartan offers attractive economic features for the healthcare provider and has a positive impact on the cardiovascular morbidity and health-related quality of life of these patient populations.

Simvastatin: between clinics and health economics

Statins reduce the incidence of cardiovascular events, one of the most important public health problems and among the main leading causes of death. Their use has been increasing in the last decade and today they represent the first drug class in terms of public expenditure. In view of the introduction of generic simvastatin in the Italian market, this paper outlines a pharmacological and economic profile of this compound. Despite two decades of life, simvastatin remains competitive with other HMG-CoA inhibitors, inducing a dose-dependent, up to 43% cLDL reduction. In clinical trials evaluating hard endpoints, simvastatin treatment achieved a strong reduction of cardiovascular events, revascularization procedures and mortality. Review of the main published pharmacoeconomic studies on simvastatin consistently indicated good cost/effectiveness ratios in most geographic contexts; convenience of this therapy increases along with baseline cardiovascular risk. Among available statins inducing equivalent cholesterol reductions, generic simvastatin has the lowest daily costs. Assuming stable market volume, an estimated cost saving for the Italian National Health Service of about 1 million Euro per year is expected from the introduction of the generic drug. Further cost savings may accrue for a potential switch from more expensive statins to simvastatin. Albeit individual responses to statins are unpredictable, the choice to start with lower cost molecules can limit initial drug investment and dampen the negative financial impact of treatment interruptions and switches.

The clinical and economic value of lovastatin in the primary prevention of cardiovascular disease

HMGCoA-inhibitors (statins) lower plasma cholesterol through interference with the rate-limiting enzyme in the endogenous synthesis process. Since their introduction in the early 90’s, the clinical attitude towards cardiovascular (cv) risk reduction has evolved from the attention to single risk factors to a more comprehensive global risk evaluation, and thus the indications of statins have broadened from the secondary prevention in hypercholesterolemic patients to include primary prevention in mildly and moderately hypercholesterolemic, or even normocholesterolemic patients, provided their global cv risk is considered high (typically, an estimated major cv event probability greater than 20%). Italian drug utilization data show that a small proportion of patients who could benefit from statins do actually receive them, contributing to the persistence of the clinical and economical burden of cv disease, the leading cause of mortality; since statins have proved effective, and cost-effective, in cv prevention, a more widespread use appears desirable, but requires high investments in pharmaceutical costs. This article defines a clinical profile of lovastatin, a statin with a solid efficacy and safety record only recently introduced into the Italian market despite it has been the first to become clinically available abroad. Among available statin formulations appropriate for target cholesterol reductions up to 30%, which apply to a significant proportion of statin therapy candidates, lovastatin 20 mg is marketed at the lowest price. Although the individual response to the different statins is highly unpredictable, determining a mandatory empirical molecule- and dose-finding strategy on the single patient, from the societal point of view the choice to start with lower cost molecules, among options that on average are equally-effective, may limit initial drug investment and dampen the impact of resource waste secondary to treatment interruptions and switches.