A cost-effectiveness and budget impact analysis of apremilast in patients with psoriasis in the Italian setting.

Aims: The aim of this study was to conduct a cost-effectiveness analysis, as well as a budget impact analysis, on the use of apremilast for the treatment of adult patients with moderate-to-severe plaque psoriasis (defined as a psoriasis area severity index [PASI] ≥ 10), who failed to respond to, had a contraindication to, or were intolerant to other systemic therapies, within the Italian National Health Service (NHS).Materials and methods: A Markov state-transition cohort model adapted to the Italian context was used to compare the costs of the currently available treatments and of the patients' quality of life with two alternative treatment sequences, with or without apremilast as pre-biologic therapy. Moreover, a budget impact model was developed based on the population of patients treated for psoriasis in Italy, who would be eligible for treatment with apremilast.Results: Over 5 years, the cost-effectiveness analysis showed that the strategy of using apremilast before biologic therapy was dominant compared with the sequence of biologic treatments without apremilast. In addition, it is important to underline that the use of apremilast slightly increases the quality-adjusted life years gained over 5 years. Furthermore, within the budget impact analysis, the strategy including apremilast would lead to a saving of €16 million within 3 years. Savings would mainly be related to a reduction in pharmaceutical spending, hospital admissions and other drug administration-related costs.Conclusion: These models proved to be robust to variation in parameters and it suggested that the use of apremilast would lead to savings to the Italian healthcare system with potential benefits in terms of patients' quality of life.

Age- and risk-related appropriateness of the use of available influenza vaccines in the Italian elderly population is advantageous: results from a budget impact analysis.

INTRODUCTION: Nowadays, four different types of influenza vaccines are available in Italy: trivalent (TIV), quadrivalent (QIV), MF59-adjuvanted (aTIV) and intradermal TIV (idTIV) inactivated vaccines. Recently, a concept of the appropriateness (i.e. according to the age and risk factors) of the use of different vaccines has been established in Italy. We conducted a budget impact analysis of switching to a policy, in which the Italian elderly (who carry the major disease burden) received the available vaccines according to their age and risk profile. METHODS: A novel budget impact model was constructed with a time horizon of one influenza season. In the reference scenario the cohort of Italian elderly individuals could receive either available vaccine according to 2017/18 season market share. The alternative scenario envisaged the administration of TIV/QIV to people aged 65-74 years and at low risk of developing influenza-related complications, while aTIV/idTIV were allocated to high-risk 65-74-year-olds and all subjects aged ≥ 75 years. RESULTS: Switching to the alternative scenario would result in both significant health benefits and net budget savings. Particularly, it would be possible to prevent an additional 8201 cases of laboratory-confirmed influenza, 988 complications, 355 hospitalizations and 14 deaths. Despite the alternative strategy being associated with slightly higher vaccination costs, the total savings derived from fewer influenza events completely resets this increase with net budget savings of € 0.13 million. CONCLUSIONS: An immunization policy in which influenza vaccines are administered according to the age and risk profile of Italian elderly individuals is advisable.

Cost-consequences evaluation between bivalent and quadrivalent HPV vaccines in Italy: the potential impact of different cross-protection profiles.

OBJECTIVES: Two human papillomavirus (HPV) vaccines are currently available: a bivalent HPV-16/18 and a quadrivalent HPV-6/11/16/18 vaccine. The vaccines may have different sustained- and cross-protection levels against non-vaccine oncogenic HPV-types. This study investigated the potential difference in clinical and economic impacts provided by two HPV vaccines in Italy. METHODS: A prevalence-based model estimated the potential net difference in HPV-related lesions (abnormal pap smear, cervical intraepithelial neoplasia (CIN), cervical cancer (CC) and genital warts (GW)) and associated costs generated by the two vaccines. Incidence and treatment costs were obtained from Italian and European sources. Vaccine efficacy rates were based on published data for each vaccine. Lifetime vaccine efficacy was assumed. Results are reported over one year after reaching a steady state. Sensitivity analyses were performed on the lesion incidence, vaccine effectiveness, treatment costs and sustained protection. RESULTS: The bivalent vaccine would prevent an additional reduction of 7976 abnormal pap smears; 601 CIN1; 1826 CIN2/3 and 295 CC cases compared to the quadrivalent vaccine while 25,848 genital wart cases would be prevented by the quadrivalent vaccine. The additional cost averted with the bivalent vaccine was estimated at €2,385,354 per year compared to the quadrivalent vaccine. The most influential parameters were CC- and GW-related costs and the difference in sustained protection. CONCLUSIONS: Our model suggests that, in the Italian setting, the bivalent vaccine would prevent more precancerous and CC lesions than the quadrivalent vaccine. This translates into a greater cost averted for the bivalent vaccine, which could completely offset savings in GW-related costs associated with the quadrivalent vaccine.

[Methodological aspects of clinical and economic impact of vaccine interventions and HTA. Focus on HPV vaccination]. / Aspetti metodologici della valutazione di impatto clinico ed economico negli interventi vaccinali in HTA. Focus sulla vaccinazione anti-HPV.

The aim of the present study is to analyze the methodological and technical aspects of Health Technology Assessment (HTA) as a tool for the clinical and economic impact of vaccine interventions, describe and comment the main studies at the national level, with a particular focus on HPV vaccination. The work was conducted in 3 phases: a) revision of the scientific literature, strictly linked to methodologies adopted in different studies on economic evaluations on HPV vaccines and analysis of Guidelines for building models for the economic assessment; b) analysis of the peculiarities and critical elements of economic evaluations in the field of vaccinology, from the clinical and epidemiological point of view, as well as the recognition of lack of knowledge on HPV infection dynamics; c) a comparative analysis of the two italian studies and of the results coming from them. Many differences between studies were found. Nevertheless, there is a general agreement on the economic profile of HPV vaccination for adolescent girls, if compared with the actual practice on the prevention of cervical carcinoma (pap-test screening). All the models showed a significant impact in terms of reduction of the incidence of cervical carcinoma and related mortality, in the long run, as well as a reduction of pre-cancer lesions and abnormal Pap tests. HTA approach has been recently recognized as a tool for decision making in vaccinology, and its methodologies and procedures are currently debated by public health experts. There is a strong need to continue the work in improving the model techniques of economic evaluations concerning HPV vaccination, as well as the adoption of homogeneous methods and standards, with the aim of helping the decision process in the field of Public Health.

Determination of endocrine disrupting chemicals in environmental solid matrices by extraction with a non-ionic surfactant (Tween 80).

A readily applicable method based on extraction by aqueous non-ionic surfactant solutions (Tween 80) and RP-HPLC coupled to fluorescence detection, has been developed for the simultaneous determination of the phenolic endocrine disrupting chemicals (EDCs) nonylphenol (NP), nonylphenol monoethoxylate (NP1EO) and nonylphenol diethoxylate (NP2EO) and bisphenol A (BPA) in environmental solid matrices. Clean up of sample extracts was performed on Si-C18 solid phase extraction (SPE) cartridges. The overall Tween 80 extraction-SPE-RP-HPLC procedure was validated for accuracy and precision by analyzing sediment samples spiked with known amounts of EDCs. Recoveries for NP, NP1EO, NP2EO and BPA and limits of detection are in agreement with conventional extraction methods. The developed methodology was successfully applied to the analysis of target compounds in Italian river sediments, river suspended matter and benthonic macroinvertebrate organisms (oligochaetes Lumbriculus variegatus). Results confirmed that this relatively simple procedure performed satisfactorily in the determination of phenolic EDCs in environmental solid matrices of different complexity and that it can be a suitable alternative method to conventional systems even for routine analyses.

Clinical-practice recommendations for the management of bowel obstruction in patients with end-stage cancer.

The paper highlights a series of questions that doctors need to consider when faced with end-stage cancer patients with bowel obstruction: Is the patient fit for surgery? Is there a place for stenting? Is it necessary to use a venting nasogastric tube (NGT) in inoperable patients? What drugs are indicated for symptom control, what is the proper route for their administration and which can be administered in association? When should a venting gastrostomy be considered? What is the role of total parenteral nutrition (TPN) and parenteral hydration (PH)? A working group was established to review issues relating to bowel obstruction in end-stage cancer and to make recommendations for management. A steering group was established by the (multidisciplinary) Board of Directors of the European Association for Palliative Care (EAPC) to select members of the expert panel, who were required to have specific clinical and research interests relating to the topic and to have published significant papers on advanced cancer patients in the last 5 years, or to have particular clinical expertise that is recognised internationally. The final constitution of this group was approved by the Board of the EAPC. This Working Group was made up of English, French and Italian physicians involved in the field of palliative care for advanced and terminal cancer patients; and of English, American and Italian surgeons who also specialized in artificial nutrition (Dr. Bozzetti) and a professor of health economics. We applied a systematic review methodology that showed the relative lack of RCTs in this area and the importance of retrospective and clinical reports from different authors in different countries. The brief was to review published data but also to provide clinical opinion where data were lacking. The recommendations reflect specialist clinical practice in the countries represented. Each member of the group was allocated a specific question and briefed to review the literature and produce a position paper on the indications, advantages and disadvantages of each symptomatic treatment. The position papers were circulated and then debated at a meeting held in Athens and attended by all panel members. The group reviewed all the available data, discussed the evidence and discussed what practical recommendations could be derived from it. An initial outline of the results of the review and recommendations was produced. Where there were gaps in the evidence, consensus was achieved by debate. Only unanimous conclusions have been incorporated. Subsequently the recommendations were drawn together by Carla Ripamonti (Chairperson) and Robert Twycross (Co-Chair) and refined with input from all panel members. The recommendations have been endorsed by the Board of Directors of the EAPC. It was concluded that surgery should not be undertaken routinely in patients with poor prognostic criteria, such as intra-abdominal carcinomatosis, poor performance status and massive ascites. A nasogastric tube should be used only as a temporary measure. Medical measures such as analgesics, anti-secretory drugs and anti-emetics should be used alone or in combination to relieve symptoms. A venting gastrostomy should be considered if drugs fail to reduce vomiting to an acceptable level. TPN should be considered only for patients who may die of starvation rather than from tumour spread. PH is sometimes indicated to correct nausea, whereas regular mouth care is the treatment of choice for dry mouth. A collaborative approach involving both surgeons and physicians can offer patients an individualized and appropriate symptom management plan.

[The health care market: what possible competition?]. / Il mercato della sanità: quale concorrenza possible.

The subject of competition in health care exceeds the scientific journals being discussed in almost each public debate on the health care system. In this paper the elements characterising economic competition will be defined in comparison with the particular characteristics of the health care market. The peculiar features of that market require attention to be paid to the equity of the system, to the competitive mechanisms which are not completely evaluated and to the failures of the public bureaucracy still operating. The principal models of competition found in the literature are illustrated and some experiences as UK and Sweden are shown. Some elements of competition are proposed for the Italian National Health Service (INHS) with some rules for the possible implementation.

Methods for evaluation of the direct and indirect costs of long-term schizophrenia.

Two approaches can be used to estimate the cost of schizophrenia. Prevalence-based cost provides an estimate of the direct and indirect economic burden incurred in a period of time as a result of the prevalence of schizophrenia during the same base period, most often a year. Incidence-based cost represents the lifetime cost resulting from the illness. Different examples of studies applying the 2 methods are illustrated, by stressing the advantages and the pitfalls of both. The incidence-based approach is the most appropriate for the purpose of making decisions about which treatment to implement. Cost analysis of lifetime schizophrenia requires reliable data on service use and treatments and particular methodological instruments. In particular, since schizophrenia is in many cases a chronic disease, pharmaco-economic evaluation should also be applied using an incidence-based approach rather than a short period of treatment.

Cost-effectiveness in the hospital use of antibiotics: introductory considerations.

A cost-effectiveness analysis was performed for three antibiotic drug therapies in pneumonia and bronchopneumonia: broad spectrum penicillins, III generation cephalosporins and ceftriaxone. The study was based on records from 117 patients in 9 general medical departments in North and Central Italy during 1989. Costs included direct cost of drugs, staff, accommodation, and other hospital costs. Effectiveness was measured radiographically as clinical cure, interruption of therapy or death. The effectiveness and shorter duration of therapy with ceftriaxone in respect to the other treatments, produced a 15.18% savings of hospital resources compared with other III generation cephalosporins, and a 14.76% savings compared with broad spectrum penicillins. This is a provisional conclusion requiring confirmation with a larger number of patients and randomized trials.

The cost of hospital stay for operable breast cancer.

The cost of the first hospital stay for operable breast cancer was deducted by analysing a random sample of 100 admissions to the National Institute of Cancer during the period January-December 1989. The aims of the study were: (1) to describe and calculate the cost component of the stay; (2) to analyse whether any procedure, service rendered or stage of the pathology might explain differences in the total costs of the stay; and (3) to acquire a better knowledge of the organizational aspects to be improved. With an average length of stay of 14.1 days, the overall total cost observed was 4.9 million lira (US $3.800, 1989 US dollars). A significant correlation between total cost and duration of stay was found (R2 = 0.982), while no or very little correlation was found between cost and the anatomical extent of disease (TNM stage) and different cost items (laboratory, imaging tests, operating room, etc.). Two homogeneous groups of cases were found: patients with quadrantectomy and patients with mastectomy. The cost of the latter was 40% greater than that of the former (P < 0.001) with a length of stay 52% longer (p < 0.001). This study does not concern the costs immediately following the stay, which namely are higher for the quadrantectomy because the radiotherapy outpatient procedures. Attention should be paid to reducing the length of stay, keeping waiting time for organizational procedures to a minimum during the stay.

Cost-effectiveness comparison of single and multiple-dose antibiotic treatment of lower uncomplicated urinary tract infections.

This study analyzed the cost-effectiveness of antibiotic treatments of different durations for acute cystitis in non-pregnant females. Questionnaires were sent to 400 practitioners evenly distributed throughout Italy. Data are reported from 2,069 patients. The clinical bacteriological efficacy at 10-15 days was 86.4% for single-dose treatment with fosfomycin-trometamol (FT), and 81.8% for the multiple-dose antibiotics group (MDAG). Disappearance of symptoms occurred in 2.1 days with FT and 3.4 days with MDAG. With FT 93.8% of patients were free of adverse events and 86.9% with MDAG. Analysis of the cost-effectiveness indicators for cure rate and absence of adverse events showed that treatment costs were similar for all antibiotics. FT needed less time interval for symptoms to disappear with a slightly higher cost than for MDAG, which had a better cost/effectiveness ratio.

[Economic efficiency and effectiveness in health care: the economist's perspective]. / Efficienza economica ed efficacia nella sanità: la prospettiva dell'economista.

The debate on the efficiency of the health care system in Italy requires a developing dialogue between clinicians, epidemiologists and health economists. In this perspective the meaning of economic efficiency and its relationship with effectiveness are presented, either at production unit level either at system level. Application of criteria of efficiency is not independent from value judgements. The conflict between clinical freedom and controls on health care expenditure have ever been and it may not be eliminated, but compounded by expliciting the criteria of choice and by defining the responsibilities of health policy makers and clinicians. An example is represented by the recent Oregon's experiment. In the agenda of the future change of the Italian National Health Service, mechanisms of cost-effectiveness resource allocation criteria are suggested to be included.

Cost evaluation of chronic schizophrenic patients during the first 3 years after the first contact.

This study was performed in Italy, where mental health care is largely provided by the Government-financed Italian National Health Service (INHS). Since 1978, outpatient services and psychiatric beds in general hospitals have replaced psychiatric hospitals, which have not been permitted to admit new patients. The direct costs of three cohorts of 20 chronic schizophrenic patients were evaluated according to incidence data for a 3-year period. The analysis focused in particular on services provided by public institutions. The average cost per patient during this period following first contact-admission was $9,612 (1989 U.S. dollars), which is low compared to costs in other countries. The cost distribution between inpatient and outpatient services was different from other studies and showed that, in Italy, hospital expenses covered approximately 50 percent of total direct INHS costs. The length of time between onset and first contact-admission showed a significant association (p less than 0.01) with INHS costs during the 3 years. A significant association (p less than 0.05) also was found between the Scale for the Assessment of Positive Symptoms (SAPS) global symptom "delusions" evaluated after 5 to 7 years and the average INHS costs during the 3 years of the study.

Cost-Effectiveness Analysis of Induction Regimens Containing Anthracyclines in Adult Acute Myelogenous Leukemia.

A cost-effectiveness analysis was performed to evaluate the impact on hospital costs of two alternative regimens, idarubicin + cytarabine and daunorubicin + cytarabine, in the induction treatment of newly-diagnosed patients with acute myeloid leukemia (AML). In evaluating the economic effects the perspectives of both hospital doctors and administrators were taken into account in order to achieve better value for money spent. For this study, the comparative results from four recently published randomized clinical studies were used as the source of clinical data. Data on the duration of hospitalization, hospital procedures and AML treatment costs were obtained from the patient records of two haematological centers. The idarubicin induction regimen appeared to be more cost-effective than that of daunorubicin in achieving complete remission, especially when costs are linked to response rate. Although several methodological issues in terms of economic evaluation still need to be solved, this type of study might offer a social contribution to the problem of the efficient allocation of resources in the health care sector.

Determination of linear alkylbenzenesulphonates, alkylphenol polyethoxylates and nonylphenol in waste water by high-performance liquid chromatography after enrichment on octadecylsilica.

An enrichment procedure involving percolation through octadecylsilica cartridges was applied to the extraction of linear alkylbenzenesulphonates (LASs), alkylphenol polyethoxylates (APEOs) and nonylphenol (NP) from treated and untreated municipal waste waters. The analytes were quantitated by reversed-phase high-performance liquid chromatography with UV-fluorescence detection. Recoveries higher than 80% were obtained from the analysis of biologically treated waste waters. The method allows rapid, precise and reliable determination of LASs and APEOs at concentrations as low as 20 and 4 micrograms l-1, respectively.