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INTRODUCTION: Prostate cancer (PC) is a very common tumor among men: in Italy its prevalence in 2006 was 0.9%. Androgen deprivation therapy is a way to treat hormone-responsive PC by decreasing testosterone levels. GnRH-analogues, including GnRH-agonists and GnRH-antagonists, are effective for this purpose. AIM: This article presents a cost-effectiveness analysis based on a semi-Markov model comparing the GnRH-antagonist degarelix and GnRH-agonist leuprolide in the treatment of hormone-dependent advanced prostate cancer from the perspective of the Regional Health Service in Veneto Region (Italy). MATERIALS AND METHODS: Effectiveness data were retrieved by a 12-month phase III non-inferiority clinical trial, comparing degarelix and 7,5 mg leuprolide in 610 patients treated for hormone-dependent prostate cancer. Epidemiological data came from a national database and were referred to Veneto Region. The values of the healthcare resources were calculated using regional and national prices (€ 2012). The model considers 3 exhaustive and mutually exclusive health status: first-line treatment, further-lines treatment and death. It lasts 10 years, with 28 days per cycle. The entry in the model is hypothesized at the age of 70 (the age with most PCs in Veneto Region). Effectiveness endpoints were life years saved and quality-adjusted life years, using 3% social discount rate. The incremental cost per QALY was related to the range of acceptability proposed by the Associazione Italiana di Economia Sanitaria (€ 25,000-40,000). The budget impact was calculated on a 5-year time horizon. Univariate and probabilistic sensitivity analyses were performed on every hypothesis of the model. RESULTS: Degarelix resulted in minor costs if compared to 7.5 mg leuprolide (€ 20,511.64 vs 22,256.49). The cost-driver was chemotherapic care (32.45% degarelix vs 44.30% 7.5 mg leuprolide). Life years saved were the same for both the alternatives (5.58), while QALYs obtained were higher in degarelix vs. 7.5 mg leuprolide (4.41 vs. 4.10). QALY better data probably could results from greater delay to disease progression in castrate resistant phase with degarelix than comparator and also due to superior symptoms relief. Therefore degarelix is dominant compared to the agonist. The probability for degarelix to be cost-effective increases with the increasing of the threshold for incremental QALY, being 69.95%, 93.76%, 95.55%, and 97.42% for threshold values equal to € 0, € 25,000, € 40,000, and € 100,000, respectively. The use of degarelix in Veneto Region instead of 7.5 mg leuprolide would result, after a five-year period, in total savings for the Regional Health Service equal to € 4,783, considering the treatment of 259 patients. CONCLUSIONS: In the treatment of hormone-dependent advanced prostate cancer PC, degarelix is thought to be an economically rational investment of resources for the Regional Health Service of Veneto Region because it’s dominant, in term of cost-effectiveness, to the comparator (agonist) thanks to superior QALY and reduced costs.

OBJECTIVE: To simulate haemophilia A (HA) real-life management and compare the cost of different treatment strategies, both with plasma-derived and recombinant factor VIII (pdFVIII and rFVIII, respectively), from the perspective of the Italian NHS. METHODS: A discrete event (micro-)simulation (DES) model was developed to reproduce every possible HA patient clinical pathway: on-demand (OD) treatment of bleeding, continuous or discontinuous prophylaxis (PRO) with FVIII, inhibitors-tolerance-induction treatment (ITI), surgery in case of severe disability. Patient characteristics, treatment indications and disease evolution were modeled basing on data available in clinical literature in order to represent the actual state of art of HA management. In addition to the baseline scenario, reproducing current HA management, alternative strategies were simulated to explore the impact on the cost borne by the Italian NHS for these patients. Only differential direct sanitary costs were considered in the simulation, with a 3.5% discount rate. RESULTS: Baseline scenario results show difference between patients treated with pdFVIII and those treated with rFVIII: mean lifetime HA patient management cost was estimated at € 1,332,373 with pdFVIII treatment, compared with € 2,013,222 for rFVIII. The saving is due mainly to the lower acquisition cost of pdFVIII. Total medical costs are strongly and positively correlated with HA severity: cost per patient increases from € 86,269 (mild HA) to € 1,509,231 (severe HA) for patients treated with pdFVIII and from € 147,900 to € 2,621,540 in patients treated with rFVIII. All analyses conducted in the study lead to the conclusion that the use of pdFVIII is much less expensive than rFVIII, but therapeutically equivalent. CONCLUSION: Management of HA patients is complex and difficult to optimize; although involving a limited number of patients, lifetime management costs for the Italian NHS are extremely high. The main advantage of this model lies in the capability of estimating the economic impact of different strategic choices and economic/regulatory constraints.

Chronic constipation is a common disorder, especially in women. Options available for different subgroups of constipation are limited and in most cases unsatisfactory. The most severe forms of chronic constipation often require the use of laxatives in high doses or the use of invasive therapies. The introduction of a new drug, such as prucalopride, active in promoting intestinal transit, can help to improve the therapy of patients with chronic idiopathic constipation who have not found relief from previous treatment with laxatives. In this review, after a brief discussion of pathophysiology and pharmacotherapy of chronic constipation, we evaluate the pharmacological profile, therapeutic and cost of prucalopride, recently authorized in the EU countries and also available in Italy for the treatment of chronic constipation in women who did not benefit from the use of laxatives

Multiple sclerosis (MS) is a chronic autoimmune disease, which affects the central nervous system and is the leading cause of chronic disability in young adults. Especially in the most common form characterized by relapses and remissions (RRMS), MS is a major burden on the NHS and society at a cost of illness per year for Italy estimated at 1.5 billion euros. The DMT (Disease-Modifying Therapies) when used continuously since the diagnosis of the disease have proved effective in reducing the risk of relapses, slowing the progression of the disease, reducing the consumption of health resources, especially hospitalizations, with a significant savings on healthcare costs. High rates of adherence have been associated with DMT not only to improved clinical performance, but also to a significant reduction in costs associated with the consumption of health resources. Because some recent studies have shown that the use of IFNβ-1a IM leads to better adherence to therapy and a significant savings in hospitalizations, outpatient visits, and also on the access to the PS, it is desirable that in Italy the use of IFNβ-1a IM will become ever greater. In this way, we can assume that we can achieve a significant saving in direct health care costs that affect the NHS, as has been observed in some foreign studies in which adherence to treatment was associated with a reduction in the average annual cost per patient between 33 and 65%.

HBV infection in Italy is frequently underestimated, raising the risk of important complications, such as cirrhosis and hepatocellular carcinoma, and thus increasing mortality. In infections phases requiring treatment, it’s possible to choose among the currently available drugs: interferons, nucleoside and nucleotide analogues. Entecavir is a nucleoside analogue able to maintain a high genetic barrier, and to reduce the viral load < 300 copies/ml in 67% of HBeAg-positive patients and in 90% of HBeAg-negative patients after 48-weeks treatment, improving also necroinflammatory grade and fibrosis degree. In spite of the high cost of the confection, entecavir induces a saving in health costs because of the decrease in the disease progression. If compared, through pharmacoeconomic models and analysis, to tenofovir, a nucleotide acid considered equivalent in the first-line monotherapy of HBeAg-positive patients and in the long-term treatment of HBeAg-negative patients by the current international and Italian guidelines, it seems favourable in terms of safety and consequently in terms of costs of adverse events spared. However further studies are required: in particular direct comparative studies are still lacking.

Hyperphosphatemia is recognized as a principal mineral disorder in chronic kidney disease (CKD) that leads to the development of secondary hyperparathyroidism. Approximately 70% of patients with end-stage renal disease (ESRD) and dialysis have hyperphosphataemia, which is associated with renal osteodystrophy, metastatic calcification and increased mortality and morbidity. Despite dietary restriction and dialysis, most patients will require a phosphate-binding agent to treat this condition.Lanthanum carbonate is an new, potent, selective, no-resin, non-calcium phosphate binder that retains high affinity for phosphate over a wide pH range, does not bind bile acids or contribute to metabolic acidosis. Taken with food, it is well tolerated. It is poorly absorbed and does not require functioning kidneys to be removed from the body. There is no evidence from current studies that it accumulates to biologically significant levels in tissues. Lanthanum carbonate has been shown in clinical studies of up to 6 years to be an effective, well-tolerated phosphate binder. Lanthanum carbonate controls hyperphosphataemia without increasing calcium intake above guideline targets and has the potential to reduce pill burden and increase patient compliance compared with other phosphate binders. Reported adverse effects are mainly gastrointestinal, and do not differ from those of calcium carbonate. The new phosphate binders, lanthanum carbonate and sevelamer, have increased the possibilities for serum phosphate control, at the expenses of significant increases in costs. The cost-effectiveness of lanthanum carbonate has been assessed by three different studies. A recent analysis, conducted on the perspective of the UK NHS, shows it is cost-effective to follow current treatment guidelines and treat all patients who are not adequately maintained on calcium carbonate (serum phosphorus above 5.6 mg/dl) with second-line lanthanum carbonate. This is particularly the case for patients with serum phosphorus above 6.6 mg/dl. A retrospective analysis, performed on IHCSI data base (USA), and a prospective study conducted in Spain show that lanthanum carbonate is cost-effective as compared with sevelamer, requiring less number of tablets, a fact that might improve adherence, and that probably explains better results with lower costs.

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 ICU hospital lengths of stay (LOS), as compared to standard TPN regimens. Here we present a pharmacoeconomic evaluation of alanyl-glutamine dipeptide in critically ill patients admitted to Italian Intensive Care Units (ICUs). 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 evaluated the alternatives from the point of view of the hospital. Simulated clinical outcomes are death and infection rates in ICU, death rate in general ward, and hospital LOSs. One-way and probabilistic sensitivity analyses are performed by varying all uncertain parameter values in a plausible range. Results: alanyl-glutamine dipeptide results more effective and less costly than standard TPN: reduced mortality rate (23.55% ± 15.2% vs 34.50% ± 2.06%), infection rate (15.91% ± 3.95% vs 18.97% ± 3.94%), and hospital LOS (25.47 ± 0.26 vs 26.00 ± 0.27 days) come at a lower total cost per patient (23,922 ± 3,249 vs 24,145 ± 3,361 Euro). Treatment cost is completely offset by savings on ICU and antibiotic costs. The cost/effectiveness acceptability curve indicates an estimated 78% probability of alanyl-glutamine dipeptide resulting dominant and a 90% probability of resulting cost/effective for a willingness to pay up to 1,500 Euro for one patient death avoided. Conclusions: alanyl-glutamine dipeptide is expected to improve clinical outcomes and to do so with a concurrent saving for the hospital.

Three case reports, where an “equivalent” drugs is prescribed, are described: a patient treated with lanzoprazole, a man with acute myocardial infarction and a young man with epilepsy. These reports are emblematic of the doubts and problems that doctors have to afford in the choice of a generic drug instead of a branded drug. The Author examines not only clinical, legislative and economical aspects of prescription of generic drugs in the Italian context, but also common questions that patients may ask when a generic drug is prescribed.

The main aim of this retrospective study was to perform a pharmacoeconomic analysis of long term use of darbepoetin-α (DARB) after switch from erythropoietin-ß (EPO-ß) in treating chronic nephropathy-induced anemia in dialysed patients. Secondary objective was the assessment of the actual EPO-ß-to-DARB dose conversion factor. We extracted data of 78 patients who have been treated with EPO-ß for at least 6 months and then switched to DARB from the database of the dialysis center of the Asti (Piedmont, Italy) hospital. From these, we selected 47 patients (23 males and 24 females) who completed a 120-weeks follow-up treatment with DARB. All patients were treated with a dose adjustment schedule to keep haemoglobin levels in the range 11-12g/dl. Pre-switch EPO-ß administration was thrice a week, while DARB was administered once a week, both via intravenous. Initial DARB dose has been calculated on the basis of the theoretical 200:1 conversion factor. Actual cumulative EPO and DARB consumption was recorded for all patients. Drug costs were valued according to purchasing prices for the Italian National Health System (October 2006). In the 24 pre-switch weeks the average cost (±SD) per patient for EPO-ß was € 2,309.86 (±1,434.78). In the 120 weeks of follow-up the average cost (±SD) per patient for DARB/24 weeks ranged from a minimum of € 1,487.09 (±1,125.51) to a maximum of € 2,125.73 (±1,546.85). The switch of 47 patients to DARB produced an overall net saving for the dialysis centre estimated in 119,540.72 Euro/120 weeks, under the hypothesis that EPO-ß semester costs remain constant: the conversion from EPO-ß to DARB has the potential to maintain long term good haemoglobin control and induces significant savings for the National Health System. However the dosage should be adjusted on an individual basis in order to avoid excessive fluctuation of Hb concentrations. The actual conversion factor resulted on average higher than theoretical factor settling to 240-280:1.

Despite considerable improvements in the last two decades, chemotherapy-induced nausea and vomiting (CINV) remains a frequent and very bothersome medical problem. It is estimated that about one half to two thirds of all chemotherapy-treated patients experience CINV, the frequency depending on the chemotherapy regimen used and on patient-specific features. The impact of CINV, which may be acute, delayed or even anticipatory in experienced patients, on health-related quality of life (HRQoL) is substantial in all domains. Until recently, effective treatment choices included corticosteroids and first-generation 5-HT3 antagonists, which have been supported by aprepitant, the first clinically available NK1 antagonist, and by palonosetron, considered the first second-generation 5-HT3 antagonist for its high receptor-subtype selectivity and affinity and long plasmatic half-life. In this paper, clinical pharmacology of the latter drug is briefly outlined and recent Italian papers on the epidemiology and HRQoL impact of CINV are reviewed, as well as national pharmacoeconomic evalutations conducted on palonosetron. The role in therapy of palonosteron and its potential for improved clinical, HRQoL and economic outcomes is discussed.

Psoriatic arthritis is an inflammatory and possibly destructive form of arthritis; left untreated, psoriatic arthritis can be a progressively disabling disease. The arthritic manifestations often include debilitating disease of the hands and feet, as well as painful inflammation of the tendon insertions and arthritis of the spine. The most common treatments prescribed for the psoriatic arthritis are nonsteroidal anti-inflammatory drugs (NSAIDs), COX-2 inhibitors, corticosteroids and disease-modifying antirheumatic drugs (DMARDs). Due to a recently suggested role of the tumour necrosis factor (TNFα) in the pathogenesis of psoriatic arthritis, new therapies specifically blocking TNFα have been investigated. Aim of the present study is to compare cost/effectiveness (CEA) and cost/utility (CUA) ratios of anti-TNF medications currently available on the Italian market: etanercept, infliximab and adalimumab. The evaluation was conducted through the development of a single Markov model. Clinical data were obtained from three Phase III trials attesting the clinical efficacy of the biological therapies. Both cost/effectiveness and cost/utility analysis were implemented through the deterministic evaluation and the probabilistic evaluation, in order to assess the convenience for the Italian National Healthcare Service. Adalimumab appears to be cost effective for the treatment of psoriatic arthritis, especially considering the incremental cost/effectiveness ratio (ICER) and the incremental cost/utility ratio (ICUR); the results suggest that ICER and ICUR values of adalimumab over etanercept is definitely lower than the maximum acceptable willingness-to-pay value. Moreover, compared with infliximab, adalimumab is less costly and more effective.

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer and its medical and economical burden represents a serious matter in Europe and Usa, due to its high mortality rates and drug costs. Lung cancer is responsible for about 30% of cancer death in men and women; in Europe only about 8 per cent of people with lung cancer survive for 5 years. At present combination chemotherapy based on cisplatin or carboplatin associated with paclitaxel, vinorelbine or gemcitabine is the state of the art for the treatment in patients with stage IIIb or IV NSCLC. Aim of this study was to compare the cost-effectiveness of paclitaxel/carboplatin (PCb), gemcitabine/cisplatin (GC) and vinorelbine/cisplatin (VC) in the perspective of the Italian National Health Service. Therefore we perfomed a semi-Markov decision model mainly based on clinical results from the Italian Lung Cancer Project. The model included differential direct medical costs registered for two years from starting chemotherapy, using tariffs valid for 2005. Benefits was measured by years of life saved (YOLs). The model also allowed to estimate only costs accrued over the period of time, performing a cost-minimisation analysis. According to cost-effectiveness analysis, VC is dominated because it’s more costly and less effective than GC. On the contrary, combination chemotherapy with GC is more inexpensive but less effective than paclitaxel/carboplatin (PCb): in this case we compared the incremental cost-effectiveness ratio (ICER) with a maximum acceptable willingness-to-pay (WTP) value. In the base scenario the ICER of PCb over GC treatment is 52,326 euro/ YOLs, which is definitely lower than the maximum acceptable WTP value. Sensitivity analyses confirmed the robustness of the results from cost-effectiveness analysis in the base scenario.

Pharyngotonsillitis (FT) and acute otitis media (OMA) are among the most frequent infectious diseases of the childhood and exact a heavy toll on the Italian national health service (INHS), families and society as a whole. In case of established or suspected bacterial origin, current treatment guidelines for FT recommend 5-10 days of oral antibiotics, chosen among available penicillins, cephalosporins, or macrolides. More controversial appears the systematical use of an antibiotic for OMAs, but prevalent expert opinion suggests use of the same agents. In this paper, an economical appraisal of five of the most prescribed oral antibiotics for these indications in Italy (cefaclor, amoxicyllin, amoxicyllin/clavulanate, clarithromycin and azithromycin) is provided. The evaluation was conducted through the development and implementation of two distinct models, constructed to reflect national treatment patterns of these infections. Clinical and economical data were obtained from several sources: literature review, including published meta-analyses, consultation of an expert panel and, most importantly, from the results of a specific questionnaire-based survey completed by 136 pediatricians, based throughout Italy. The models were run to conduct both cost-effectiveness and cost-minimization analyses, that consistently indicated cefaclor and amoxicyllin to be substantially equivalent in terms of total costs to the INHS and the Italian society, but significantly more convenient than amoxicyllin/clavulanate, claritrhomycin or azithromycin. Extensive probabilistic sensitivity analyses confirmed the robustness of this conclusion.

Significant advances in the management of hypercholesterolemia have been made possible by the development of statins, 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors. More recently, statins have demonstrated benefit in primary and secondary prevention of cardiovascular disease also in patients without hypercholesterolemia. Therefore statins help to reduce the impact of cardiovascular disease on morbility, mortality and social costs. Statins inhibit HMG-CoA reductase competitively, reduce LDL levels more than other cholesterol-lowering drugs, and lower triglyceride levels in hypertriglyceridemic patients. Prescribing statins as first line therapy in management of hypercholesterolemia as a part of a more comprehensive prevention program of cardiovascular disease is widely recommended by international guidelines (e.g. National Cholesterol Education Program - NCEP - Adult Treatment Panel - ATP- III reports). Currently in Italy there are five available statins: atorvastatin, fluvastatin, pravastatin, rosuvastatin and simvastatin; each of them presents some differences in physical and chemical characteristics (solubility), pharmacokinetics (absorption, proteic binding, metabolism and excretion) and pharmacodinamics (pleiotropic effects). Compared to other statins, fluvastatin extended-release (RP) 80 mg provides an equal efficacy in lowering total cholesterol and low-density lipoprotein cholesterol (LDL-C), with an important action on triglyceride (TG) levels and superior increases in HDL-C levels, reducing the incidence of major adverse cardiac events (MACE). Aim of this study is to outline an updated therapeutic and pharmacoeconomic profile of fluvastatin, particularly regarding extended-release (RP) 80 mg formulation.

Darbepoetin (DARB), a human erythropoietin with improved pharmacological parameters (longer half life and a dose-response relationship independent from the route of administration) is a new treatment option for chronic nephropathy-induced anemia that in many Italian dialysis centers is substituting older erythropoietins, mainly due to greater ease of use. At current prices and at the theoretical and recommended 200:1 dose conversion factor, DARB pharmaceutical cost ranges from –9% to +17% of EPO cost. In this monocentric study, real drug consumption and related actual costs of a pre-switch semester with EPO were analysed and compared to the first two post-switch semesters with DARB therapy. Furthermore, erythropoetic response was recorded and related to drug exposition levels, in order to establish a real life EPO:DARB dose conversion factor. In this experience, the conversion factor was estimated in at least 250-280:1, depending on the method adopted for the estimation. The initial dose, chosen on the basis of the recommended conversion factor, induced an excessive erythropoietic response, which was generally followed by a dose reduction and successive titration to target desired Hb levels, generating the spiraliform dose-response curve associated with delayed feed-back mechanisms. The pharmacoeconomical analysis, conducted in the perspective of the public health service, indicated that the choice of substituting DARB for EPO in the treatment of chronic kidney failure-associated anemia is univocally convenient, the former being less costly and more effective.

Levofloxacin is a newer fluoroquinolone, with broad spectrum of antibacterial activity and good tolerability. This drug has a pharmacokinetic and pharmacodynamic profile that allows a once-a-day administration and offers the potential for intravenous-to-oral switch therapy. Due to these characteristics, the principal guidelines recommend it, as an option for the empirical therapy of patients with mild or more severe community acquired pneumonia (CAP), acute exacerbation of chronic bronchitis (AECB), complicated urinary tract infection (cUTI) and skin and soft tissue infection (SSTI). These pathologies are common causes of morbidity and mortality and place a large burden on medical and economic resources, specially if hospitalization is required. The implementation of a critical pathway, based on levofloxacin use and on a risk prediction rule to establish the need for hospitalization, has the potential to decrease healthcare resource consumption without impairment of clinical outcomes, with respect to conventional management. The possibility of switch therapy allows to reduce length of hospital stay, with a saving in both direct and indirect costs, and an increase in patient satisfaction. In summary, when used according to appropriateness criteria and for approved indications, levofloxacin offers favorable economic features for the healthcare provider, whilst guaranteeing a positive impact on patient functioning and quality of life.

Type 2 diabetes mellitus (DM) and peripheral arterial disease (PAD) are two very relevant cardiovascular (CV) risk factors, which can often be found concurrently in the same patient. The DAVID trial, a double-blind, randomized, aspirin(ASA)-controlled study, has demonstrated that the use of picotamide, a thromboxane A2 synthase and receptor dual inhibitor, is associated with lesser CV morbidity and mortality in this type of patients in comparison to ASA, considered the standard antiplatelet agent. In order to estimate clinical and economic impacts of picotamide in the Italian health care setting, we developed a pharmacoeconomic model based on clinical data from DAVID and national economic parameters and demographics. The base case scenario, which reflects current prices and reimbursement policy (i.e. ASA fully paid for, picotamide out-of-pocket for patients) yielded an incremental cost/effectiveness ratio (ICER) of about 8,500 euro/year of life (YOL) saved, which falls below conventionally adopted willingness to pay thresholds. This cost, however, is totally born by the patient, while the savings on health care expenditures for avoided events (and less ASA) benefit the national health service (NHS). These results may help the physician in explaining the consequences of this choice to his/her patients, facilitating a fully-informed choice. The availability of a theoretical model allowed to explore some alternative scenarios, that indicate that the ICER can be further lowered and the economical burden better distributed through policy changes. In conclusion, the pharmacoeconomic model indicated that picotamide is likely to be a cost/effective option for CV mortality and morbidity prevention in patients with concurrent type 2 DM and PAD and that the level of adoption of this strategy will depend on willingness to pay and policy priorities of the NHS and patients themselves.

Current international guidelines for the management of immuno-compromised patients with febrile neutropenia recommend a systemic antimicrobial therapy if fever hasn’t receded after three days of antibiotic treatment. Amphotericin B remains the gold standard because of its broad spectrum fungicidal action and minimal resistance development risk. Nonetheless, therapeutic use of the standard formulation, Amphotericin B deoxycholate, is limited by its toxicity, especially on the kidneys. To counteract this, amphotericin B has been encapsulated in liposomes, a process which reduces its toxicity and allows higher doses to be given. Three lipid formulations have been developed and are now available in most countries: amB colloidal dispersion (ABCD), amB lipid complex (ABLC), and liposomal amB (L-AmB). These lipid formulations differ in pharmacodynamics and pharmacokinetics, and can’t therefore be considered interchangeable. Besides, they are more expensive than Amphotericin B deoxycholate. Aim of the study is to perform a cost/effectiveness analysis (CEA) comparing L-AmB (3mg/kg/die or 5mg/kg/ die) and ABLC (5mg/kg/die) as first-line antimicrobial empirical treatments in immuno-compromised patients with febrile neutropenia resistant to broad spectrum antibiotics. Secondly, we present a cost-minimization analysis (CMA) of the considered alternatives, assuming the same efficacy for all treatments. At the end we value the principal cost items from the point of view of the Italian Health Service, with a particular focus on the economic burden caused by adverse reactions.

Current practice guidelines for the treatment of COPD recommend the use of combined inhaled corticosteroids and long-acting bronchodilators in severe and very severe patients (GOLD stages III and IV). OBJECTIVES: To analyze the economical and clinical impact of this recommendation, the affordability of its widespread application, as well as the relative pharmacoeconomical performance of the available options for severe and very severe COPD in Italy. METHODS: Published data on the Italian COPD population were fitted in a disease progression model based on a Markov chain representing severity stages and death. Alternative therapeutic options (salmeterol/ fluticasone - SF, formoterol/budesonide - FB, salmeterol alone - S, fluticasone alone - F and control - C) were represented as competing arms in a decision tree. Efficacy data from international trials were expressed in terms of risk reduction. Clinical parameters used were number of exacerbations and symptom-free days. Direct and indirect costs were considered and valued according to present prices and tarifs. The analyses were conducted from National Health System, societal and patient perspectives with time horizons of 1,5, and 10 years, and lifelong. RESULTS: The yearly total direct costs of treating COPD patients in Italy is estimated in approximately 7 billion Euro, with a mean cost/patient/year around 2,400 Euro. Mean survival of the cohort is 11,5 years. The C and F strategies are dominated (i.e. are associated with worse outcomes and higher costs) by all alternatives. S/F and F/B are the most effective strategies, with a slight clinical superiority of the latter, but are also marginally more expensive than S. Incremental cost/effectiveness of S/F vs. S is 679,55 Euro/avoided exacerbation and 3,31Euro/gained symptom-free day. CONCLUSIONS: The recommended use of combined inhaled corticosteroids and long-acting bronchodilators for severe and very severe COPD patients, as compared with current practice, has the potential of improving clinical outcomes without increasing health care costs.

Despite the fact that an effective vaccine against hepatitis B virus (HBV) has been available for over 30 years, the worldwide prevalence of this infection is still very high. Until recently, there were only two effective therapeutic options for chronic hepatitis B (CHB), interferon and lamivudine, but both are considered suboptimal therapies, for different reasons. Adefovir dipivoxil (ADV) is the oral prodrug of adefovir, an acyclic nucleotide analogue that demonstrated virological and clinical effectiveness against HBV in experimental and real world settings. In this paper the main pharmacological and clinical evidence of ADV in CHB is reviewed. Health care economics data on the direct costs of CHB in different countries are presented and potential economical consequences of its introduction in Italy are discussed.

OBJECTIVES: To estimate the pharmacoeconomical impact of preventing recurrent upper respiratory tract infections (URTIs) with OM-85, a non-specific immunostimulating agent, in at-risk children. METHODS: Implementation of a decisional model. The evaluation of effectiveness (number of prevented URTIs/therapeutic cycle) was based on weighted average of the results of four randomized, double-blind, placebo-controlled trials identified by literature reviewing. The clinical events considered in the model were natural resolution of the infection, onset of complications (acute otitis media, sinusitis, others) and their evolution. Baseline event probabilities were derived by reviewing published data in the literature. URTI-related direct and indirect costs supported by patient, by Italian health system and by community were structured according with the principal guidelines and implemented with current Italian prices and tariffs. The cost/ effectiveness of OM-85 was calculated for five scenarios, differing in the number of therapeutic cycles, grade of patient co-payment and other secondary assumptions. Sensibility analyses were performed to evaluate the model robustness. RESULTS: Immunostimulation with one cycle of OM-85 prevented on average 1,60 URTI/patient in six months (RR = 0,515). In the basic scenario, this preventive action induced savings for 107,42 euro/patient in the perspective of the patient’s family, for 48,52 euro/patient in the perspective of Italian health system and for 231,26 in the community perspective. Sensibility analyses confirmed the robustness of basic scenario results. Threshold analyses showed that OM-85 prophylaxis is economically convenient as long as more than 7% of infections are prevented or global cost of one episode of URTI is greater than 10,00 euro. CONCLUSIONS: Non-specific immunotherapy with OM-85 induces a reduction in the incidence of URTIs in atrisk children with a concurrent saving for patient and health system.

In the modern age, advances in processes, technology and clinical imperatives generated an evolution of the health care organization, particularly regarding hospitals, born as generic shelter and poor house. Nowadays the availability of high technologies and the intensity of intervention on patients are the main factors to warrant the modern hospital for acute care. This evolution trend brings out the need for new models of health care, focused on people’s different request about assistance (e.g. day-hospital, day-surgery, integrated home care, hospice). The present study gives an outline of the Italian situation, which is deeply changed in the latest years. New models of heath care emerged in Italy, as it had previously in the United States and other European countries, as able to improve assistance and reduce costs: the average hospital stay decreased, while the number of day-hospital and day-surgery increased. In spite of the rise observed in the last 3-4 years, both integrated home care and hospice availability remain still limited, especially considering the high potential request of the elderly population and the oncologic patients.

Sulodexide is a highly purified glycosaminoglycan approved for leg ulcers treatment. It contains two principal components: heparan sulfate, a fast-moving heparin fraction, (80%) and dermatan sulfate (20%). Sulodexide is available as an oral agent and as an injectable preparation. Its pharmacological action is obtained by dose-dependent coagulation factors inhibition: dermatan sulfate upgrades the physiological action of a selective thrombin inhibitor, heparin cofactor II, and heparan sulfate depresses activated factor X, via an increase of antithrombin III action. The antithrombotic action is enhanced by platelet aggregation inhibition and by the activation of the fibrinolytic system. This paper summarizes the results of some of the main trials that evaluated sulodexide in the treatment of peripheral occlusive arterial disease and venous leg ulcers; a trial on prevention of recurrent deep venous thrombosis with sulodexide is also reviewed. We analyzed data about the clinical and economical impact of chronic venous insufficiency with a particular attention to the cost of medication, hospitalization and management of leg ulcers. The hypothetical savings correlated to the reduction of leg ulcers incidence and healing time attainable with sulodexide have been estimated. A comparison between the different acquisition costs of the drugs frequently used to treat leg ulcers is also provided. Finally we reviewed some quality of life trials in which the psychological and sociological influence of the disease and its treatments on the patient are assessed.

Outpatient parenteral antibiotic therapy (OPAT) has become an increasingly used therapeutic modality during the last 20 years. Reasons for this rapid growth include OPAT’s many patient benefits as well as the development of new technologies and well-documented cost savings. Recently the Italian Drug Agency (AIFA) has revised the list of drug’s limitations and indications; particularly two notes about OPAT (n. 55- n.56) have been modified. These new notes can assume at least a double significance: if on the one hand they try to put a check on the overuse and misuse of OPAT, steering physicians towards a better utilization of parenteral antibiotics, on the other they allow to prescribe OPAT also in case of non-ordinary infections, promoting development of more structured OPAT programmes. Prescribing physicians should be aware of a number of aspects of OPAT which distinguish it from other forms of therapy: multiple factors must be taken into account, including the probable infecting organism, the pharmacodynamic and pharmacokinetic properties of candidate drugs, the capabilities of patients who will receive OPAT and of their caregivers. The Infectious Diseases Society of America (IDSA) Guidelines have been elaborated to help physicians thorough assessment of OPAT suitability, even if they need to be adapted to many variables in each treatment setting. Aim of the present study is to re-consider the main microbiologic, clinical and pharmacoeconomic criteria supporting the prescription of an outpatient parenteral antibiotic therapy after the publication of the new AIFA notes.

Antibiotics are commonly used to treat major inflammatory complications of diverticular disease, but apparently there is no rationale for the use of antibiotic therapy in uncomplicated disease, where an inflammatory component is by definition excluded. Some observations suggest a possible role of gut microflora in determining some symptoms related to diverticular disease: bacterial overgrowth, amplifying gas production and bacterial degradation of fibres, could determine bloating, pain and high fecal density. Therefore a beneficial antibiotic action on diverticular disease symptoms can be hypothesized. In this paper pharmacokinetic, pharmacodinamic and therapeutic potential of an intestinal antibiotic, rifaximin, are reviewed. Rifaximin is a rifamycin derivative which acts by inhibiting bacterial ribonucleic acid (RNA) synthesis. It is virtually unabsorbed after oral administration and in vitro data indicate it to possess a broad spectrum of action; bacterial resistance during exposure to rifaximin has been reported but its clinical importance remains to be fully defined. The results of placebo-controlled clinical trials show that cyclic administration of rifaximin is more effective in reducing symptoms and in preventing complications than fibre supplementation alone; the drug appears to be well tolerated and safe. We consider the clinical implications and economical impact of diverticulosis on the Italian National Health System and the patient, with a particular attention on the cost of hospitalization, surgery and global management of diverticulitis and other common disease complications. The hypothetic savings correlated to the reduction of complications incidence, attainable with rifaximin use have been calculated and the comparison between the different acquisition costs of the drug frequently used to treat the diverticular disease is provided. Finally we reviewed some quality of life trials in which the psychological and sociological influence of the disease symptoms and treatments on the patient are assessed.

Tramadol is one of the preferred weak opioid agonists in the management of chronic pain, due to a good efficacy and safety profile, to a particularly low interference with cardiovascular and respiratory functions and a low dependence and abuse potential. The successful use of tramadol, nevertheless, is often limited by low patient compliance, a consequence of gastrointestinal side effects (mainly nausea and vomiting) and frequent dosing regimens, among other reasons. In this paper, clinical studies conducted on slow-release formulations of tramadol and other strategies for compliance improvement in various pain conditions are reviewed. From the examined literature, it appears that the strategy with the best compliance is the use of slow release (SR) formulations, which simplify dosing regimens and tend to have a somewhat better tolerability, and a slow dose escalation, which improves tolerability. The advantages of SR formulations have to be weighed against the superior acquisition cost and the slower onset of analgesia. A frame for the evaluation of the clinical and economical advantages and disadvantages of SR versus immediate release formulations of tramadol is also proposed.

Dialysis-associated hyperphosphatemia has been treated with chelating calcium salts, in particular with calcium carbonate. A new option for the management of this problem is represented by sevelamer, a chelating agent which contains no calcium and no metals. Sevelamer and calcium carbonate are more or less equally effective and tolerated. The prolonged use of sevelamer instead of calcium carbonate, nevertheless, reduces calcemia and C-reactive protein levels, with a consequent reduction in myocardial infarction, angina pectoris and other peripheral vasculopathies. The limit to the wide-spread use of sevelamer is in its very high acquisition cost, as compared to the alternative. In this article, a semi-markovian pharmacoeconomical model for the comparison of clinical and economical outcomes of sevelamer and calcium carbonate is presented. The analysis is conducted in the perspective of the Italian health system (SSN). Clinical data are derived from published studies and integrated with expert panel estimates, cost data are relative to the Italian setting. The incremental cost-effectiveness analysis indicated that sevelamer is more costly, but also more costeffective: a one month gain in survival costs the SSN additional 2710 Euro, a value inferior to the conventionally accepted willingness-to-pay of industrialised countries. The majority of this excess cost is derived from the gain in survival, and consequent increase in dialysis costs. Thus, the choice of using sevelamer instead of calcium carbonate is even more justified from an ethical point of view. Sensibility analyses confirmed the robustness of the basic scenario results.

Parecoxib sodium is the first selective COX- 2 inhibitor to be available for parenteral administration. This pharmaceutical feature, alongside its favorable efficacy and safety profile, makes the new drug particularly suitable for simple and effective management of post-surgical pain. Aim of this work is to describe the pharmacoeconomical profile of the drug in the Italian setting, focusing on the comparison with parenteral ketorolac, the most widely prescribed treatment for post-surgical pain in Italy. The first part of the article describes the most important pharmacological characteristics of parecoxib and reviews the main efficacy and safety studies that were performed on patients presenting with post-surgical pain. A similar article about parecoxib was published on “Farmeconomia e percorsi terapeutici” 2003; 4(1): 39-50. At that moment, the price to the public wasn’t yet fixed and therefore the pharmacoeconomical analysis was based on estimated price. Moreover, during this year, extra studies were published on the efficacy of parecoxib on patients with post-surgical pain. For these reasons, we intend to present here an updated version of the profile.

The introduction of low molecular weight heparins (LMWHs) has opened new possibilities for the costeffective management of the thrombotic risk associated with surgical procedures, allowing prophylaxis – and sometimes even treatment of established deep vein thrombosis – on a out-patient basis. This article gives a brief overview of the pharmacological and clinical features of LMWHs, focusing on the differences with unfractionated heparin (UFH), which allow great simplification of dosing regimens and settings without disadvantages in terms of efficacy or safety. In fact, some data indicate that LMWH might be better tolerated than UFH. The overcoming of the need for hospitalization for pre- and post-surgical thromboprophylaxis has important economical implications and is leading to a different formation of health care costs in these patients. The clinical and economical consequences of the pharmacological differences between LMWHs and UFH are analyzed with a “value matrix”, a pharmacoeconomical technique for preliminary evaluations. The last section examines Italian drug acquisition costs and compares the economical values of the recommended dosing regimens of LMWHs available on the national market for the prevention and the treatment of deep vein thrombosis. Bemiparin is the most convenient LMWH for all approved indications. In the management of surgery-associated thrombotic risk, no clinically relevant differences among LMWHs have been demonstrated. Thus, bemiparin appears to be the most logical choice in a costminimization strategy.

Orphan drugs definition should be related to prevalence criteria. In Europe the prevalence criterion is 5/10.000. These drugs are called “orphans” because the pharmaceutical industry has little interest under normal market conditions in developing and marketing products intended for only a small number of patients. For this reason governments have emphasized the need for economic incentives to encourage drug companies to develop and market orphan drugs. Aim of this study is the analysis of the contributing factors involved in the price definition of orphan drugs in Italy, focusing on the case of DepoCyte®, a new orphan drug recently approved by the European Medicines Agency. DepoCyte® is a slow-release formulation of cytarabine designed for intrathecal administration in the treatment of neoplastic meningitis due to metastatic cancers. It maintains cytotoxic concentrations of free cytarabine in the cerebrospinal fluid for more than 14 days following a single injection. In two randomized clinical trials DepoCyte® was compared to standard formulation of cytarabine, showing a better time to neurologic progression and survival trend in favor of DepoCyte®, associated with an improved mean change about quality of life in Karnofsky performance score. The innovative technology and the efficacy of DepoCyte® allow to frame some interesting pharmacoeconomical consequences: the results of the present work showed that DepoCyte® is more expensive but also more effective than standard formulation, and the new formulation-correlated improvement in the patients’ quality of life seems to justify the difference between the costs of the two alternatives.

Bisphosphonates (BPs) are osteoclast-mediated bone resorption inhibitors and the nature of the groups attached to the central carbon atom determines the drug potency. Neridronate is an injectable aminobisphosphonate, structurally similar to alendronate and pamidronate, authorized for the treatment of osteogenesis imperfecta (OI). This drug has often been used to treat other pathologies, as an off-label option, to increase tolerability and ameliorate compliance, partly because the management of orally administered bisphosphonates, with their gastrointestinal side effects, results complicated. In this paper pharmacokinetic, pharmacodinamic and main placebo-controlled clinical trials on OI patients are reviewed. The available scientific evidence demonstrates the neridronate efficacy to improve spine and hip bone mineral density, to lower markers of skeletal turnover and to decrease fracture incidence, compared with controls. We also report clinical trials results and data about the effect of intravenous infusions of neridronate in patients with postmenopausal osteoporosis, Paget’s disease and rheumatoid arthritis. Finally, we consider the economical impact of chronic and incapacitating pathologies, like osteogenesis imperfecta, on family’s total income and the influence of the disease on quality of life of pediatric and adult patients.

Tramadol is an effective central analgesic with a dual mechanism of action: antagonism on mu-opioid receptors and inhibition of serotonin and norepinephrine reuptake. In this paper a pharmacological, clinical and economical profile of its use in pain management is provided. Tramadol has proven effective in the treatment of moderate and severe pain associated with acute and chronic conditions of different ethiology, at oral or parenteral doses of about 50-100 mg every 4-6 hours. The maximal daily dose should not exceed 400 mg, less in case of liver or kidney dysfunction. Tramadol has low potential for physical or psychological dependence; the minimal likelihood of provoking typical opioid adverse events represents an advantage over other morphine-like agents. From a pharmacoeconomical point of view, tramadol prescription appears to be efficient: the comparisons conducted in the management of post-surgical pain have shown tramadol to be more convenient than the studied alternatives. Overall, tramadol appears to be a safe and effective drug for the management of pain and it is one of the most relevant week opioids to be used in the second step of the pain management latter proposed by the WHO. The recent introduction of generic tramadol permits to choose among more products and allows to obtain savings on the cost of managing acute and chronic painful conditions.

The incidence of nosocomial infections from Gram-positive pathogens has been increasing in the last two decades, alongside the development of antibiotic resistance in many bacteria. Glycopeptidic drugs are the most widely used options for these patients, but some bacterial strains with low sensibility to vancomycin and teicoplanin are starting to emerge, warranting careful monitoring and control of nosocomial and also community- acquired infections. This paper outlines a clinical, therapeutic and economic profile of linezolid, the first drug of the only new antibiotic class developed in the last thirty years. In clinical trials, linezolid has demonstrated very promising efficacy and safety in the treatment of antibiotic-resistant infections, in particular those caused by methicillin-resistant staphylococci (MRSA), obtaining greater or equal clinical and microbiological success rates than the standard options. Linezolid, as most newer drugs, has higher acquisition costs than the alternatives, but also bears interesting features that may modify the formation of infection treatment costs. In particluar, linezolid is very well absorbed after oral administration, allowing the planning of sequential iv/os strategies that have the potential to reduce health care costs and to improve the quality of life of the patients by shortening the length of hospitalization. Economic evaluations have demonstrated that this advantage is not merely theoretical, but that it can be achieved in real practice. In particular, linezolid has been shown to be more cost-effective than teicoplanin and vancomycin in the treatment of hospitalized, MRSA-related nosocomial pneumonia and severe infections.

Uncontrolled epilepsy has a significant negative impact on patient’s quality of life, on his emotional well-being and his social functioning. Seizure places an undue economic burden on the patient and community. The increased costs are direct and indirect (e.g.,inpatient care and loss of earnings associated with time lost from work). Levetiracetam is a new antiepileptic drug used as adjuntive therapy in the treatment of refractory epilepsy. Its nonconventional mechanism of action is not completely understood, but preclinical studies suggest that its antiepileptic action.may depend on a reversible, saturable and stereoselective binding site in CNS membranes. In this paper, we review the main clinical and economic data available in the scientific literature. Levetiracetam has a favourable pharmacokinetic profile characterised by rapid and nearly complete absorption, very low potential for drug interactions and a prolonged pharmacodynamic effect that permits twice-daily dosing. Several placebo-controlled clinical trials have demonstrated that its efficacy has enabled many patients who were refractory to treatment with other antiepileptic drugs to achieve long-term seizure freedom; furthermore in levetiracetam trials the frequency of adverse events is low and withdrawal rates are comparable with those of placebo. A cost/effectiveness analysis compared direct medical costs of levetiracetam add-on therapy with maintenance of standard therapy alone within the UK National Health Service. A 1-year dose escalation decision model was set up in refractory patients who failed to respond to two or more other currently available therapies, with seizure freedom selected as the measure of effectiveness. Available pharmacoeconomic data show that the incremental cost of treating patients with levetiracetam is low when compared with the benefits of seizure freedom, at least in the UK. Furthermore, current studies suggest that this antiepileptic drug has a potential as first-line treatment for many types of epilepsy and in many different patient populations.

Losartan is an angiotensin II receptor antagonist (ARB) that has been proven effective and well tolerated in the treatment of hypertension and in the reduction of global cardiovascular risk, but is more expensive than many alternatives. The present paper resumes its main pharmacological and clinical features, as a basis for analyzing its economical value. Despite the universally accepted relevance of good blood pressure control, hypertension is still undertreated and poorly controlled. Among the main reasons for this, poor adherence to therapeutic regimens plays a relevant role. Losartan and ARBs have been shown to be associated with compliance rates superior to those observed with any other antihypertensive drug class, due to an adverse events incidence similar to placebo and scarcity of relevant pharmacological interactions, and can therefor improve the cost-effectiveness of hypertension treatment. Several trials have indicated that losartan determines clinical benefits that go beyond its haemodynamic effect, such as renal protection, reduced incidence of stroke and cognitive improvement. The addition of losartan to conventional hypertensive therapy in diabetic patients with nephropathy has been estimated to induce net health cost savings in different settings, a relevant result, as very few medical interventions have demonstrated such a potential. To understand the real economical value of losartan, its drug acquisition costs have to be balanced against the benefits deriving from antihypertensive effectiveness, high compliance and non-haemodynamic target organ protection.

Sodium parnaparin is a low molecular weight heparin (LMWH). The introduction of this drug class has represented a medical advancement in the prevention and therapy of thromboembolic pathologies, as they maintain the same efficacy of unfractionated heparin, but with simplified dosing regimens and reduced side effects. Parnaparin has demonstrated its thromboprophylactic efficacy on both high- and moderate risk surgical patients, besides resulting effective in treating established deep vein thromboses and thrombosis-associated phlebopathies. Alongside these clinical advantages, parnaparin and other LMWHs allow outpatient or home-based therapy of a large number of subjects that should otherwise be treated in hospital, with important savings of health resources and enhanced quality of life for the patients. In Italy, parnaparin drug acquisition cost is the lowest among all LMWHs for the majority of their applications, permitting marginal savings in health costs at the same efficacy level. In summary, the use of parnaparin in thrombotic pathologies has very good efficacy and safety profiles, and has positive clinical and economical outcomes for patients, health system and society as a whole.

Invasive aspergillosis (IA) is a common and life-threatening infectious complication of immune system depression. Amphotericin B deoxycholate (AMB-d) has been considered standard therapy for IA for over 40 years, despite the fact that success rates rarely exceed 40% and adverse effects are quite common. At present two more recent pharmacological agents are available for the treatment of IA: liposomal amphotericin B (L-AMB) and voriconazole (VOR). In this article, we present a pharmaco-economical study comparing the relative costeffectiveness of 5 alternative strategies in the treatment of invasive aspergillosis, analysed from the point of view of the Italian hospital: administration of L-AMB as first line therapy, followed by no rescue treatment in case of failure (L-AMB I°); administration of L-AMB as first line therapy, followed by VOR in case of failure (LAMB I° + VOR rescue); AMB-d as first line, followed by L-AMB in case of failure (L-AMB rescue); AMB-d as first line, followed by other antifungals as needed (AMB-d I°) and VOR as first line, followed by rescue treatments in case of failure (VOR I°). The cost-effectiveness analysis was conducted using decision tree modelling techniques: efficacy data were obtained from published clinical trials; costs parameters were fitted on the Italian setting. The results indicate that two strategies, L-AMB rescue and VOR I°, are dominated, i.e. induce higher costs and lower success rates than the alternatives. The three remaining strategies are neither dominated nor dominate the others, but are associated with different clinical and economical outcomes: AMB-d I° has the lowest total cost, but also the highest cost-effectiveness ratio and the lowest overall efficacy; L-AMB I° has the best cost-effectiveness, but requires the willingness to pay 2,100 euro for each additional success; L-AMB I° + VOR rescue is the most effective treatment, but this choice is associated with incremental costs of 17,200 euro for each additional success, compared with L-AMB I°. In conclusion, our analysis indicates that for clinical, economical and ethical reasons the best option in the treatment of IA is the administration of L-AMB as first line therapy, thus limiting the use of VOR to the rescue of the patients not cured by this approach.

[Editorial in Italian]

The term inflammatory bowel diseases (IBD) refers to two distinct clinical entities: Crohn.s disease and ulcerative cholitis, two chronic and non-specific disorders of unknown origin. Although quite uncommon and usually not life-threatening, IBDs have a strong economical impact, as they tend to affect patients in high productivity ages and require long and demanding therapies, medical and sometimes surgical. The pharmacological approaches to IBD treatment include aminosalicylates, corticosteroids and immunosuppressive agents. Aminosalicylic acids are the most widely used agents for maintaining remission and for the cure of mild-tomoderate forms of IBDs. This paper outlines the main pharmacological and clinical properties of one of these drugs, mesalamine (mesalazine). Mesalamine is the active moiety of sulfasalazine, an effective but not always tolerated agent. Mesalamine is available in several pharmaceutical forms, to be administered either by the oral or by the rectal route. As the therapeutic action of aminosalicylates is ascribed to their topical action on the inflamed intestine, while the adverse effects are believed to be caused by the systemically adsorbed (mainly in the first tract of the small bowel) fraction, slow-release formulations are usually preferred. From an economical point of view, mesalamine appears to have a moderate acquisition cost, widely offset by the savings induced on direct sanitary and, most importantly, indirect costs of IBDs. In particular, the availability of a generic drug with advanced colon-delivery technology provides the physician with the opportunity to treat patients with the best available technology at a reasonable price.

Oxatomide is an antiallergic drug with a double mechanism of action: it possesses antagonistic activity on the H1 histaminergic receptor and it inhibits the production and release of flogistic and allergic mediators by effector cells, presumably acting as a selective calcium channel blocker on these cellular types. The efficacy and safety of oxatomide have been evaluated in many studies conducted on patients affected by different clinical conditions, demonstrating remarkable flexibility. It proved to be safe and effective also in extreme ages, i.e. children under 3 months of age and elderly over 80 years. Approved indications include rhinitis, asthma, conjunctivitis, urticaria, atopic and allergic dermatitis and food allergy and intolerance. In direct comparisons, oxatomide consistently proved superior than placebo and equally or more effective than other consolidated antiallergics. The drug tolerability is good, its main side effects are drowsiness and weight gain, usually transient. Cardiac and hepatic safety data are very reassuring, as is the case for drug interaction potential. Form an economical point of view, the drug acquisition cost is acceptable, being among the lowest in its class, at equally effective doses. Overall, the efficacy in several clinical conditions, the good tolerability in most patients and the reasonable purchase cost suggest that oxatomide is characterized by excellent risk-to-benefit and cost-to-benefit ratios in the treatment of allergic pathologies.

Fluoxetine has been the first antidepressive agent of the class of selective serotonine reuptake inhibitors (SSRI) to be introduced in therapy, back in 1987. The availability of SSRIs has meant a great advance in the treatment of major depression and other neuro-psychiatric pathologies. In this paper we review the scientific and clinical research on fluoxetine that has been published in the last six years, as the prior work has been extensively examined in a review conducted on the tenth anniversary of its introduction on the market. The review focuses on cost minimization strategies that can be conducted following the introduction of low cost generic fluoxetine.

Cardiovascular disease (CVD) remains one of the leading causes of mortality and morbidity worldwide. Since several pharmacological approaches are available for the reduction of incidence and severity of cardiovascular events and health resources in modern managed care systems are limited, the evaluation of the clinical and economical consequences of any treatment is very valuable for decison-makers and physicians. In this article we present a flexible pharmacoeconomic model that permits the calculation of the marginal costeffectiveness of cardiovascular prevention with ramipril, a drug of the class of ACE-inhibitors. The clinical data used for the modelization are derived from the HOPE (Heart Outcomes Prevention Evaluation) study, a landmark cardiovascular prevention study that showed how the benefits of ACE-inhibition with ramipril go beyond the effects on blood pressure, while Italian epidemiological, demographic and economical data make the results appliable to the Italian population. The model, structured as a decision tree comparing the alternatives “to treat” or “not to treat” with Markow chains at the terminal nodes, calculates the marginal cost-effectiveness of the preventive treatment in terms of cost/year of live saved. The model is characterized by high flexibility, as it allows health decision-makers to set epidemiological and economical data in order to reflect the local population at high risk for developing cardiovascular diseas. The model was tested on a high risk population, formed by all acute myocardial infarction survivors in Italy, and indicated that life-long treatment of this patients would yield significant clinical benefits, with a cost/ effectiveness of 3,932 euro/year of life saved. This value is well below the standards that are considered acceptable, and offsprings from the partial offset of pharmaceutical costs caused by the reduction in the expenses for diagnosis and treatment of the cardiovascular events avoided with the preventive therapy.

Every drug whose copyright coverage has expired can be manufactured by a pharmaceutical company other than the one that developed it, giving rise to the market of the so-called generic drugs. It can be distinguished among two types of generic drugs: branded and unbranded, according to the choice of the manufacturer to assign it a fantasy name or to sell it with the name of the active principle, followed by the company’s name. In order to be accepted for marketing, every new drug has to pass the registration procedures of the Italian Ministry of Health, which are simplified for generics, as it’s sufficient to demonstrate the bioequivalence, considered a reliable proxy of therapeutic equivalence, of the new drug with the standard formulations it copies. The bioequivalence of two drugs depends on various parameters, related to the quality of the raw materials employed and the industrial processes they go through. There are several ways of assessing the equivalence between pharmaceutical products, and it is important the registration studies are conducted following strict rules, in order to guarantee the quality of generics, fundamental for achieving the trust of health operators and patients. The reason to be of generic drugs is essentially economic, as they bare no therapeutic innovation, and their introduction is mainly aimed to contain drug expenditures and to facilitate a competitive market, but to do so, they need to be widely accepted by the medical community and the population. In Italy, the market of generic drugs is very young and relatively underdeveloped if compared to what is observed in other industrialized countries such as the USA, Germany or UK, but it has a good expansion potential, as it also represents a chance for quality enhancement for the Italian pharmaceutical industry.

Parecoxib sodium is the first selective COX- 2 inhibitor to be available for parenteral administration. This pharmaceutical feature, alongside its favorable efficacy and safety profile, makes the new drug particularly suitable for simple and effective management of post-surgical pain. The first part of the present article describes the most important pharmacological characteristics of parecoxib and reviews the main efficacy and safety studies that were performed on patients presenting with post-surgical pain. Starting from these clinical data, the second part outlines the pharmacoeconomical profile of the drug in the Italian setting, focusing on the comparison with parenteral ketorolac, the most widely prescribed treatment for post-surgical pain in Italy. The available scientific evidence suggests that the introduction of parecoxib in the arsenal of available options for the management of this kind of patients in Italy may have a positive clinical and economical impact, despite of the higher drug acquisition price. In particular, the better tolerability shown by parecoxib in the comparison with non-selective NSAIDs would permit a reduction in the costs for the prevention and the cure of drugrelated adverse events and reduce the need for patient monitoring. Furthermore, the improved safety and the longer duration of the analgesic action could allow the management of more minor surgery patients in daysurgery units, with great economical advantages for the hospital and the health system and improved quality of life for the patients.

Osteoporosis is a disorder of bone re-modeling, characterized by loss of its micro-architecture and decreased bone density, which lead to fragility and high risk of fracture following moderate traumata. Osteoporosisrelated pathological fractures occur more frequently in post-menopausal women, and the WHO estimates that the risk of osteoporotic fractures in women is approximately 40% during lifetime. The prevention of these osteoporotic fractures is considered one of the primary objectives for the control of the economical health burden of modern societies. The first part of this paper briefly outlines the physio-pathological basis, the epidemiology, the diagnosis and the available treatment options for osteoporosis, with particular regard to those therapies that are able to reduce the incidence of pathological fractures, that represent the main cost factor of the disease. In the second part, we reviewed the economical evaluations published on the cost of illness and of the costefficacy of the treatments. The studies that have analyzed the cost of osteoporosis, although incompletely, highlight that the greatest expenditures are related to hospitalization and rehabilitation after hip fracture, while the cost for the pharmacological treatment is relatively low. The cost-efficacy and cost-utility analyses conducted on pharmacological treatment are quite heterogeneous, and therefore hardly comparable, beside being conducted in countries with different health systems; the obtained data are nor directly transferable to the Italian setting. However, it emerges that diphosphonates, estrogens and SERMs (selective estrogen receptor modulators) are among the drugs with more favorable cost/effectiveness ratio, but there is still an uncertainty in the detection of the appropriate patient groups, which is crucial for the clinical, economical and ethical optimization of prevention interventions.

In pharmacoeconomical evaluations the quantification of drug utilization has to be done on the basis of measurement units that allow comparisons among series of longitudinal and transversal data. The most common techniques used for the analysis and the comparison of drug utilization patterns are based either on the Defined Daily Dose (DDD), a unit system proposed by WHO’s Drug Utilization Research Group, or on the Prescribed Daily Dose (PDD), a statistical parameter obtained from the analysis of drug prescriptions. This article illustrates the meaning of the main indicators of drug consumption that can be build with these techniques, underlining their utility and limitations. The DDD is the conventionally established theoretical mean daily dose of a drug, referred to a way of administration and to its main indication. It is, therefore, a mere technical measurement unit that cannot be interpreted as mean prescribed or consumed dose, and even less as recommended dose. The PDD, on the contrary, is not a measurement unit but a statistical mean value, that expresses the central tendency of the prescription variability in a defined setting. Starting from Italian data on the consumption of wide-spread antibiotics, the use and interpretation of various indicators based on the DDDs and PDDs are discussed. The parameters derived with the DDD technique are suitable for monitoring drug utilization and pharmaceutical expenditure. The PDD method is more direct, indicates the mean quantities actually prescribed and permits the estimation of the total dose consumed per therapeutic cycle and of other clinically relevant parameters, but requires the acquisition of more data than the other technique does. It is also important to remark the fact that both methods can’t be directly used for economical evaluations trying to assess the efficiency of resource allocation, as they are not correlated to the clinical outcomes of the therapy.

Disease-related malnutrition, the most frequent cause of undernourishment in industrialized countries, appears to be highly prevalent among western patient populations, interesting up to 60% of the hospitalized and almost one fifth of the persons attending to the general medicine service. There are several reasons for this high prevalence, among which pathology-related causes, inadequate presentation of the meals in hospitals and institutions, and low recognition of nutritional problems by health professionals. Several studies have shown that undernourished patients have higher morbidity and mortality rates than the general population and suffer of more and more severe complications, leading to prolonged hospital stays and worse clinical outcomes. This determines a much higher Health costs, estimated in an English study as a yearly additional burden of over 7 billion £ for the National Heath Service. Nutritional interventions, such as the administration of oral supplements or enteral tube feeding, are capable to increase body mass index (BMI), that is considered the most reliable indicator of the nutritional status, muscle strength and overall psycho-physical performance, determining an improved quality of life and a reduced need for medical assistance. These functional improvements go alongside with better clinical outcomes, as shown by a reduced mortality rate, shorter hospital stays and lower incidence of complications observed after supplementation. Studies that have analyzed the economical impact of nutritional supplementation in terms of cost-benefit have shown that the cost of enteral nutritional interventions is almost negligible when compared to the associated savings in the production of the health service, mainly determined by lower hospitalization rates, shorter hospital stays, reduced costs for the treatment of complications and for the consultation of specialists. Greater awareness of the health professionals and more encouraging health policies toward nutritional interventions are required to reduce the clinical and economical impact of this unnecessarily wide-spread condition.

Pregnancy-related hypertension, intrauterine growth retardation, post-maturity and unfavorable local conditions are among the most frequent indications for labor induction. There are two competing strategies for the induction of labor in term pregnancies: formal induction with artificial rupture of the membranes and/or intravenous oxytocin on one side, and cervical ripening and induction with exogenous prostaglandins on the other. The use of prostaglandins in obstetrics relies on two pharmacological properties: the capacity of inducing the biochemical changes in the connective tissue of the cervix that lead to its maturation and the stimulation of the uterine smooth musculature. While the latter property is shared with oxytocin, the former offers great clinical advantages, in particular in those women that present an indication for labor induction but whose cervix, normally assessed with the use of the Bishop score, does not show “ripeness”, i.e. does not permit vaginal delivery. Since the acquisition cost of the prostaglandins is quite high, but the clinical benefit appears evident, several studies have analyzed the overall economical impact of their use, both as pre-induction cervical ripening agents and as induction drugs. When compared to a strategy of expectant management in term pregnancies without cervical ripeness, exogenous prostaglandin administration has proven to be more cost-effective and better accepted by the patients. Prostaglandins have also proven to be more cost-effective than oxytocin and/or amniotomy in women with an indication to labor induction and unripe cervix, due to the reduced number of induction failures and cesarean sections required with this strategy. The economical analyses that have compared oxytocin and prostaglandins in women with ripe cervices deliver more ambiguous data, but it appears that their cost-effectiveness is comparable. Furthermore, none of the reviewed studies has considered intangible costs, but it is a wide-spread opinion that induction with prostaglandins results in a more “natural” and less painful labor.