Cost-Effectiveness of Treatment Optimisation with Biomarkers for Immunotherapy in Solid Tumours: A Systematic Review.

This study investigated the health economic evaluations of predictive biomarker testing in solid tumours treated with immune checkpoint inhibitors (ICIs). Searching PubMed, EMBASE, and Web of Science from June 2010 to February 2022, 58 relevant articles were reviewed out of the 730 screened. The focus was predominantly on non-small cell lung cancer (NSCLC) (65%) and other solid tumours (40%). Among the NSCLC studies, 21 out of 35 demonstrated cost-effectiveness, notably for pembrolizumab as first-line treatment when preceded by PD-L1 assessment, cost-effective at a threshold of $100,000/QALY compared to the standard of care. However, for bladder, cervical, and triple-negative breast cancers (TNBCs), no economic evaluations met the affordability threshold of $100,000/QALY. Overall, the review highlights a certain degree of uncertainty about the cost-effectiveness of ICI. In particular, we found PD-L1 expression associated with ICI treatment to be a cost-effective strategy, particularly in NSCLC, urothelial, and renal cell carcinoma. The findings suggest the potential value of predictive biomarker testing, specifically with pembrolizumab in NSCLC, while indicating challenges in achieving cost-effectiveness for certain other solid tumours.

Reimbursed Medication Adherence Enhancing Interventions in European Countries: Results of the EUREcA Study.

Introduction: Current literature lacks detailed understanding of the reimbursement framework of medication adherence enhancing interventions (MAEIs). As part of the ENABLE COST Action, the EUREcA ("EUropen REimbursement strategies for interventions targeting medication Adherence") study aimed to provide an in-depth overview of reimbursed MAEIs currently available in European countries at national and regional levels and to pave the way for further MAEIs to be implemented in the future. Methods: A web-based, cross-sectional survey was performed across 38 European countries and Israel. The survey questionnaire was developed as a result of an iterative process of discussion informed by a desk review. The survey was performed among invited ENABLE collaborators from June to July 2021. Besides descriptive analysis, association between country income and health care expenditure, and the availability of reimbursed MAEIs were also assessed. Results: The survey identified 13 reimbursed MAEIs in nine countries: multi-dose drug dispensing (n = 5), medication review (n = 4), smart device (n = 2), mobile application (n = 1), and patient education (n = 1). The median GDP per capita of countries having ≥1 reimbursed MAEI was significantly higher compared to countries having no reimbursed adherence intervention (33,888 EUR vs 16,620 EUR, respectively; p = 0.05). Conclusions: Our findings highlight that to date only a small number of MAEIs have been reimbursed in European countries. Comprehensive health technology assessment recommendations and multi-stakeholder collaboration could help removing barriers related to the implementation and reimbursement of MAEIs.

The Effectiveness of Interventions to Evaluate and Reduce Healthcare Costs of Potentially Inappropriate Prescriptions among the Older Adults: A Systematic Review.

Potentially inappropriate prescribing (PIP) is associated with an increased risk of adverse drug reactions, recognized as a determinant of adherence and increased healthcare costs. The study's aim was to explore and compare the results of interventions to reduce PIP and its impact on avoidable healthcare costs. A systematic literature review was conducted according to Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement guidelines. PubMed and Embase were queried until February 2021. Inclusion criteria followed the PICO model: older patients receiving PIP; Interventions aimed at health professionals, structures, and patients; no/any intervention as a comparator; postintervention costs variations as outcomes. The search strategy produced 274 potentially relevant publications, of which 18 articles met inclusion criteria. Two subgroups were analyzed according to the study design: observational studies assessing PIP frequency and related-avoidable costs (n = 10) and trials, including specific intervention and related outcomes in terms of postintervention effectiveness and avoided costs (n = 8). PIP prevalence ranged from 21 to 79%. Few educational interventions carried out to reduce PIP prevalence and avoidable costs resulted in a slowly improving prescribing practice but not cost effective. Implementing cost-effective strategies for reducing PIP and clinical and economic implications is fundamental to reducing health systems' PIP burden.

Prescription Appropriateness of Drugs for Peptic Ulcer and Gastro-Esophageal Reflux Disease: Baseline Assessment in the LAPTOP-PPI Cluster Randomized Trial.

Background: Drugs for peptic ulcer and gastro-esophageal reflux disease (GERD) are among the most widely prescribed, frequently without appropriate indications. This represents an important issue, as it leads to risk of adverse events for patients and unnecessary costs for National Health Service. Aim: To assess the prescription appropriateness of drugs for GERD, in the frame of the "Evaluation of the effectiveness of a Low-cost informative intervention to improve the Appropriate PrescripTiOn of Proton PumP Inhibitors in older people in primary care: a cluster-randomized controlled study" (LAPTOP-PPI) (Clinicaltrial.gov: NCT04637750). Methods: The appropriateness of drug prescription was assessed on data collected in administrative databases, by integrating information on concomitant medications, outpatient medical and laboratory procedures and hospital discharge diagnoses, according to the reimbursement criteria provided by the Italian Medicine Agency. We analyzed data of community-dwelling people aged 65 years and over, living in the areas of Bergamo (Northern Italy) and Caserta (Southern Italy), from July 1 to 31 December 2019. Results: Among 380,218 patients, 175,342 (46.1%) received at least one prescription of drugs for GERD. All in all, we found that only 41.2% of patients received appropriate prescriptions. Conclusion: Given the potential risk of adverse drug reactions, especially in older people, educational interventions should be prompted for physicians, in order to improve the quality of prescription of drugs for GERD and, in turn, avoid unfavorable health outcomes and unnecessary costs.

Developing and piloting a communication assessment tool assessing patient perspectives on communication with pharmacists (CAT-Pharm).

BACKGROUND: Effective communication strategies in health care help to enhance patient empowerment and improve clinical outcomes. OBJECTIVE: Adapt the original Communication Assessment (CAT) instrument for the pharmacist profession (CAT-Pharm) and to test its validity and reliability in two different settings. SETTING: Five hospital pharmacies in Italy and five community pharmacies in Malta. METHOD: Pilot study involving a standardized multi-step process adhering to internationally accepted and recommended guidelines. Corrections and adjustments to the translation addressed linguistic factors and cultural components. CAT-Pharm, compared to the original CAT, maintained 10 out of the 14 items: one was slightly modified; three were changed to better fit the pharmacist role; one was added. MAIN OUTCOME MEASURES: CAT-Pharm development and testing its practicality to assess patient perceptions of pharmacists' interpersonal and communication skills. RESULTS: CAT-Pharm was tested on 97 patients in the Italian setting and 150 patients in the Maltese setting to assess the practicality of the tool and its usefulness in investigating gaps and priorities for improving pharmacist-patient communication. Results Show reliability and internal validity of the CAT-Pharm tool. The analysis of patient perceptions of communication with the pharmacist in Italy indicated differences from that in Malta. The different settings provided insight into the utility of CAT-Pharm. CONCLUSION: This study provided a valid and reliable tool that could be applied to assess patient perception of the pharmacist's communication abilities.

Assessment of surgeon communication skills from the patient perspective: A national evaluation using the Communication Assessment Tool.

OBJECTIVE: The Communication Assessment Tool (CAT) has previously been translated and adapted to the Italian context. This national study aimed to validate the CAT and evaluate communication skills of practicing surgeons from the patient perspective. METHODS: CAT consists of 14 items associated with a 5-point scale (5 = excellent); results are reported as the percent of ''excellent'' scores. It was administered to 920 consenting outpatients aged 18-84 in 26 Italian surgical departments. RESULTS: The largest age group was 45-64 (43.8%); 52.2% of the sample was male. Scores ranged from 44.6% to 66.6% excellent. The highest-scoring items were "Treated me with respect" (66.6%), "Gave me as much information as I wanted" (66.3%) and "Talked in terms I could understand" (66.0%); the lowest was "Encouraged me to ask questions" (44.6%). Significant differences were associated with age (18-24 year old patients exhibited the lowest scores) and geographical location (Northern Italy had the highest scores). CONCLUSION: CAT is a valid tool for measuring communication in surgical settings. PRACTICE IMPLICATIONS: Results suggest that expectations of young people for communication in surgical settings are not being met. While there is room to improve communication skills of surgeons across Italy, patients highlighted the greatest need in the Central and Southern regions.

Cost-effectiveness of treatment optimisation with biomarkers for immunotherapy in solid tumours: a systematic review protocol.

INTRODUCTION: The combination of biomarkers and drugs is the subject of growing interest both from regulators, physicians and companies. This study protocol of a systematic review is aimed to describe available literature evidences about the cost-effectiveness, cost-utility or net-monetary benefit of the use of biomarkers in solid tumour as tools for customising immunotherapy to identify what further research needs. METHODS AND ANALYSIS: A systematic review of the literature will be carried out according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement guidelines. PubMed and Embase will be queried from June 2010 to June 2021. The PICOS model will be applied: target population (P) will be patients with solid tumours treated with immune checkpoint inhibitors (ICIs); the interventions (I) will be test of the immune checkpoint predictive biomarkers; the comparator (C) will be any other targeted or non-targeted therapy; outcomes (O) evaluated will be health economic and clinical implications assessed in terms of incremental cost-effectiveness ratio, net health benefit, net monetary benefit, life years gained, quality of life, etc; study (S) considered will be economic evaluations reporting cost-effectiveness analysis, cost-utility analysis, net-monetary benefit. The quality of the evidence will be graded according to Grading of Recommendations Assessment, Development and Evaluation. ETHICS AND DISSEMINATION: This systematic review will assess the cost-effectiveness implications of using biomarkers in the immunotherapy with ICIs, which may help to understand whether this approach is widespread in real clinical practice. This research is exempt from ethics approval because the work is carried out on published documents. We will disseminate this protocol in a related peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42020201549.

The value of the polypill in cardiovascular disease: an Italian multidisciplinary Delphi panel consensus.

The purpose of this work was to reach the consensus of a multidisciplinary and multistakeholder Italian panel on the value of polypill in cardiovascular disease, with respect to the clinical, technological, economic and organizational dimension. A three-step modified Delphi method was used to establish consensus. Eleven experts in the area of cardiology, pharmaceutical technology, general practice, hospital pharmacy, pharmacology, and health economics participated in the expert panel. To identify existing evidence concerning the value of polypill in the prevention of patients with cardiovascular disease, a systematic literature review was carried out according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses statement guidelines. In the first round, 22 statements were distributed to the panel. Panel members were asked to mark 'agree' or 'disagree' for each statement and provide any comments. The same voting method was again used for the second round. In the first round nine statements met consensus. In the second round, 10 statements reached consensus. Overall, consensus was reached for 19 statements representing five value polypill domains: clinical, technological, economic and organizational. During a final web meeting with all panel members consensus document open points were discussed. Panel members agreed to recognize polypill as effective in reducing cardiovascular events, blood pressure and lipids, cardiovascular risk and the weight of therapy, in therapeutic adherence improvement, in the absence of differences in bioavailability between drugs administered in fixed or free combinations and the better cost-effectiveness profile compared with standard care. This document represents a knowledge framework to inform decision makers of the value of polypill in cardiovascular prevention.

Comorbidity in an Older Population with Type-2 Diabetes Mellitus: Identification of the Characteristics and Healthcare Utilization of High-Cost Patients.

Objectives: Little is known about the specific comorbidities contributing to higher costs in patients with type-2 diabetes mellitus (T2DM), particularly in older cases. We aimed to evaluate the prevalence, type, and cost of comorbidities occurring in older T2DM patients versus older non-T2DM patients, and the factors associated with high cost (HC) T2DM patients. Methods: Retrospective cohort study using information from the Campania Region healthcare database. People aged ≥65 years who received ≥2 prescriptions for antidiabetic drugs were identified as "T2DM patients." Comorbidities among T2DM and non-T2DM groups were assessed through the RxRiskV Index (modified version). T2DM individuals were classified according to the total cost distribution as HC or "non-high cost." Two sub-cohorts of HC T2DM patients were assessed: above 90th and 80th percentile of the total cost. Age- and sex-adjusted logistic regression models were created. Results: Among the T2DM cohort, concordant and discordant comorbidities occurred significantly more frequently than in the non-T2DM cohort. Total mean annual cost per T2DM patient due to comorbidities was €7,627 versus €4,401 per non-T2DM patient. Among T2DM patients identified as being above 90th and 80th percentiles of cost distribution, the total annual costs were >€19,577 and >€2,563, respectively. The hospitalization cost was higher for T2DM cases. Strongest predictors of being a HC T2DM patient were having ≥5 comorbidities and renal impairment. Conclusion: HC patients accrued >80% of the total comorbidities cost in older T2DM patients. Integrated care models, with holistic and patient-tailored foci, could achieve more effective T2DM care.

Biological therapy utilization, switching, and cost among patients with psoriasis: retrospective analysis of administrative databases in Southern Italy.

PURPOSE: The aim was to describe the current use of biological therapies among patients affected by psoriasis and to analyze a drug utilization profile in naïve patients in terms of switching and treatment costs in a Local Health Unit (LHU) of Southern Italy. METHODS: We conducted an observational retrospective cohort analysis using the health-related administrative databases of a LHU in Southern Italy covering a population of about one million inhabitants. All subjects with a main or secondary diagnosis of psoriasis who received at least one prescription of biological therapies between January 1, 2010 and December 31, 2014 were analyzed. Switching rate was evaluated in naïve patients within the first year of treatment. Drug cost was calculated for all drugs prescribed and comprised both costs for psoriasis drugs and costs for other treatments. RESULTS: About 20% of patients identified with a diagnosis of psoriasis were under treatment with biological drugs. Among 385 subjects treated with biological therapy, 51.2% were in treatment with etanercept and 33% with adalimumab. Among naïve patients, switching rate to a different biological drug, within the first year of treatment, was 7.3%. The per patient yearly drug cost was €10,536: 96.8% for psoriasis-related drugs and 3.2% for other pharmaceutical treatments. The annual average cost per patient switching from the initial treatment was €13,021, while for those who did not switch from the initial treatment, the annual average cost was €10,342, with a significant difference of about €2,680 per patient per year (p=0.002). CONCLUSION: Our data may be useful in exploring the dynamics that characterize the use of biological therapy within a specific context and to optimize the use of resources for a better management of the disease.

Different approaches to the assessment of adherence and persistence with cardiovascular-disease preventive medications.

OBJECTIVE: To assess suitability and comparability of the most common methods of treatment adherence and persistence assessment, as applied to the same pharmacy dataset. METHODS: Data on drugs prescribed for cardiovascular primary prevention to participants in the Aragon Workers' Health Study (AWHS) were collected from a regional electronic drug prescription database. Several different approaches were used to measure treatment adherence (with the medication possession ratio [MPR]) and proportion of days covered [PDC]) and persistence in new users by therapeutic subgroup. Defined daily dose (DDD) was used as a proxy of the number of days' supply, or substituted with surrogate daily dose values. RESULTS: Higher mean adherence values and proportions of adherent patients were obtained using MPR versus PDC, with additional differences depending on the approach used. The proportion of adherent patients was lowest for oral antidiabetics (14.4%-30.6%) and highest for antihypertensives (70.2%-82.1%). The use of surrogate daily dose values increased adherence for antidiabetics and statins and decreased adherence for antihypertensives. After a 1 year follow-up, treatment persistence was observed for 21.1%, 58.7%, and 29.5% of antidiabetic, antihypertensive and statin users, respectively. CONCLUSIONS: Our findings indicate that use of multiple measures of treatment adherence and persistence provides a more complete overview of medication use patterns, and certain limitations associated with DDD for some drug groups can be overcome with replacement by surrogate doses. The PDC indicator seems to provide a more accurate reflection of patient behavior and treatment continuity than the MPR. Any comparison of adherence/persistence should always consider the method used, variables analyzed, and corresponding data collection process.

Italian translation and cultural adaptation of the communication assessment tool in an outpatient surgical clinic.

BACKGROUND: The aim of the study is to translate and cross-culturally adapt, for use in the Italian context, the Communication Assessment Tool (CAT) developed by Makoul and colleagues. METHODS: The study was performed in the out-patient clinic of the Surgical Department of Cardarelli Hospital in Naples, Italy. It involved a systematic, standardized, multi-step process adhering to internationally accepted and recommended guidelines. Corrections and adjustments to the translation addressed both linguistic factors and cultural components. RESULTS: The CAT was translated into Italian by two independent Italian mother-tongue translators. The consensus version was then back-translated by an English mother-tongue translator. This translation process was followed by a consensus meeting between the authors of translation and investigators, and then by two comprehension tests on a total of 65 patients. CONCLUSIONS: Results of the translation and cross-cultural adaptation were satisfactory and indicate that the Italian translation of the CAT can be used with confidence in the Italian context.

Toward appropriate criteria in medication adherence assessment in older persons: Position Paper.

Nonadherence to medication regimens is a worldwide challenge; adherence rates range from 38 to 57 % in older populations with an average rate of less than 45 % and nonadherence contributes to adverse drug events, increased emergency visits and hospitalisations. Accurate measurement of medication adherence is important in terms of both research and clinical practice. However, the identification of an objective approach to measure nonadherence is still an ongoing challenge. The aim of this Position Paper is to describe the advantages and disadvantages of the known medication adherence tools (self-report, pill count, medication event monitoring system (MEMS) and electronic monitoring devices, therapeutic drug monitoring, pharmacy records based on pharmacy refill and pharmacy claims databases) to provide the appropriate criteria to assess medication adherence in older persons. To the best of our knowledge, no gold standard has been identified in adherence measurement and no single method is sufficiently reliable and accurate. A combination of methods appears to be the most suitable. Secondly, adherence assessment should always consider tools enabling polypharmacy adherence assessment. Moreover, it is increasingly evident that adherence, as a process, has to be assessed over time and not just at one evaluation time point (drug discontinuation). When cognitive deficits or functional impairments may impair reliability of adherence assessment, a comprehensive geriatric assessment should be performed and the caregiver involved. Finally, studies considering the possible implementation in clinical practice of adherence assessment tools validated in research are needed.

Doctors commitment and long-term effectiveness for cost containment policies: lesson learned from biosimilar drugs.

BACKGROUND: Agency is a pervasive feature of the health care market, with doctors acting as agents for both patients and the health care system. In a context of scarce resources, doctors are required to take opportunity cost into account when prescribing treatments, while cost containment policies cannot overlook their active role in determining health care resource allocation. This paper addresses this issue, investigating the effects of cost containment measures in the market of biosimilar drugs that represent a viable and cost-saving strategy for the reduction of health care expenditure. The analysis focuses on a particular region in Italy, where several timely policies to incentivize biosimilar prescribing were launched. METHODS: Drugs were identified by the anatomical therapeutic chemical classification system. Information about biosimilar drugs and their originator biological products was extracted from the IMS Health regional database. Drug consumption was expressed in terms of counting units, while expenditure was evaluated in Euro (€). The market penetration of biosimilars was analyzed by year and quarterly. RESULTS: In the Campania region of Italy, the effects of cost containment policies, launched between 2009 and 2013, showed the prescription of biosimilars strongly increasing in 2010 until prescribing levels reached and exceeded the market share of the reference biological products in 2012. After a slight reduction, a plateau was observed at the beginning of 2013. At the same time, the use of the originator products had been decreasing until the first quarter of 2011. However, after a 1-year plateau, this trend was reversed, with a new increase in the consumption of the originators observed. CONCLUSION: Results show that the cost containment policies, applied to cut health expenditure "to cure and not to care", did not produce the cultural change necessary to make these policies effective in the long run. Therefore, top-down policies for cost containment are not successful; rather, a bottom-up approach based on consensus among professionals should become the preferred option.

Self-Assessment of Adherence to Medication: A Case Study in Campania Region Community-Dwelling Population.

Objectives. The aim of the study was to assess self-reported medication adherence measure in patients selected during a health education and health promotion focused event held in the Campania region. The study also assessed sociodemographic determinants of adherence. Methods. An interviewer assisted survey was conducted to assess adherence using the Italian version of the 8-item Morisky Medication Adherence Scale (MMAS-8). Participants older than 18 years were interviewed by pharmacists while waiting for free-medical checkup. Results. A total of 312 participants were interviewed during the Health Campus event. A total of 187 (59.9%) had low adherence to medications. Pearson's bivariate correlation showed positive association between the MMAS-8 score and gender, educational level and smoking (P < 0.05). A multivariable analysis showed that the level of education and smoking were independent predictors of adherence. Individuals with an average level of education (odds ratio (OR), 2.21, 95% confidence interval (CI), 1.08-4.52) and nonsmoker (odds ratio (OR) 1.87, 95% confidence interval (CI), 1.04-3.35) were found to be more adherent to medication than those with a lower level of education and smoking. Conclusion. The analysis showed very low prescription adherence levels in the interviewed population. The level of education was a relevant predictor associated with that result.

Prescription Patterns of Antidiabetic Treatment in the Elderly. Results from Southern Italy.

The treatment of diabetes in the elderly is a major challenge both in terms of clinical management and of public health. Evidence about prescribing patterns in the elderly diabetic population is limited. The aim was to describe trends in antidiabetic drug (AD) utilization patterns in the elderly in Southern Italy with a focus on drugs for cardiovascular prevention and pharmaceutical costs. The data used for this study were obtained from pharmacy records of Caserta Local Health Authority, a province in Southern Italy with 1 million of inhabitants, comprising urban and rural areas. Subjects above 65 years who received at least one dispensing of antidiabetic between January 2010 and December 2014 were selected. Prevalence and incidence rates (%) of AD use were calculated for each calendar year and stratified by class therapy and age group. Sub-analyses by cardiovascular co-medication therapy and pharmaceutical cost analysis were performed. The prevalence rate decreases from 22.0% in 2010 to 17.5% in 2014 (p<0.001). Proportion of subjects treated with monotherapy increases over the study period (33.9% in 2010; 38.6% in 2014; p<0.001). In particular, increases the proportion of users of metformin (18.2% in 2010; 23.7% in 2014; p<0.001), while the proportion of users of sulfonylureas dropped (11.0% in 2010; 7.2% in 2014; p< 0.001). About 90% of elderly diabetic patients are treated with drugs for cardiovascular prevention. The per/patient/yearly drug costs were 2,349 ∈: 28.5% for AD therapy and 71.5% for other treatments. Trend in drug utilization patterns showed a tendency towards treatment recommendations in older adults.

Assessment and potential determinants of compliance and persistence to antiosteoporosis therapy in Italy.

OBJECTIVES: To analyze adherence to antiosteoporosis drugs (AODs) and to assess the influence of patient-related and drug-related factors. STUDY DESIGN: Observational, retrospective study. METHODS: Data on prescriptions for AODs from 2007 through 2008 were retrieved from administrative databases of 10 Italian local health units. Key measurements included compliance and persistence at 1 year. Multivariate regression analyses were performed to estimate adjusted risk ratios for compliance less than 80% and adjusted hazard ratios for no persistence. RESULTS: Of 40,004 new patients (89.9% women, mean age 69.8 years), 84.0% were treated with bisphosphonates and 74.6% of administration regimens were weekly. Overall, 75.1% of patients had suboptimal levels of compliance and 84.7% were not persistent; almost one-third had only 1 prescription. In regression analyses, younger age, change of drug, and concomitant corticosteroid therapy were significantly associated to compliance and persistence in both genders. In women, weekly and monthly regimens reduced the risk for poor compliance (sex-adjusted relative risks 0.729 [0.697-0.762], 0.846 [0.817-0.876], respectively) and no persistence (sex-adjusted hazard ratios 0.591 [0.541-0.646], 0.508 [0.461-0.560], respectively) compared with a daily regimen. CONCLUSIONS: In our study, 75% of subjects had discontinuous treatment and inadequate drug supply. Age and frequency of administration were strongly associated with adherence. Improvement is urgently needed, and occasional prescriptions represent the main target.

Proton pump inhibitors prescribing following the introduction of generic drugs.

BACKGROUND: In many countries, the introduction of generic proton pump inhibitors (PPIs) onto the pharmaceutical market increased the phenomenon of therapeutic substitution in acid-related disorders (ARDs). AIM: To investigate the treatment of ARDs in an Italian primary care setting from 2005 to 2008 by verifying: (i) dynamics of PPI prescribing; (ii) predictors of PPI switching; and (iii) healthcare resource consumption costs. METHODS: This was a retrospective cohort study of 102 general practitioners (GPs) who managed an average of 150000 inhabitants in Naples. Multilevel logistic regression was used to assess the potential predictors of both PPI switching and termination. Primary care costs were expressed as the cost of ARD management per PPI user year. RESULTS: The percentage of PPI users with ARD increased from 5·5% (2005) to 7·0% (2008) (P<0·0001), especially for dyspepsia (from 9·5% to 13·7%; P<0·0001) and chronic treatments (from 23·4% to 29·4%; P<0·0001). PPI switching rose from 13·0% to 16·7% during the period observed (P<0·0001). Calendar years, long-term treatments and gastroesophageal reflux disease were positive predictors of PPI switching. Primary care costs relating to PPI switchers increased by 61·14€ compared with nonswitchers (P<0·0001). CONCLUSIONS: The introduction of generic PPIs onto the Italian market was associated with an increasing amount of PPI prescribing related to chronic treatments, unlicensed indications (e.g. dyspespsia) and therapeutic substitutions. Growing overall costs linked to the phenomenon of PPI switching was also found. Our data support the need to assess the effects of the introduction of generic drugs on both clinical outcomes and the cost management of ARDs.

Pharmaco-economic consequences of losartan therapy in patients undergoing diabetic end stage renal disease in EU and USA.

Diabetic nephropathy is the most frequent cause of end stage renal disease (ESRD). As ESRD incidence increases continuously, more resources are needed for treatment. The objective was to evaluate the economic impact of losartan added to the standard care administered to diabetic subjects with ESRD. The analysis has involved more than 500 million inhabitants. Standard methods have been used in order to conduct an economic evaluation comparing the economic outcomes deriving from the administration of losartan added to standard care versus standard care alone in patients with type 2 diabetes mellitus (DM) and nephropathy over 3.4 years. The study was hence conducted from the perspective of the third-party payer. The clinical outcome data were based on the results from the Reduction of Endpoints in Non-Insulin Dependent Diabetes Mellitus with the Angiotensin II Antagonist Losartan (RENAAL) trial. Direct medical costs are referred to the purchase costs of losartan and to the costs of hospitalization. The costs were discounted back at an annual rate of 3%. Also sensitivity analysis was performed. The RENAAL study showed that losartan confers strong renal protection in patients with DM and nephropathy. Losartan results into cost saving in all countries considered: 3,602.98€/Italy, 4,531.35€/France, 3,019.66€/Germany, 3,949.50€/Switzer-land, and 3,855.50€/US per patient. Results are not sensitive to both clinical and economic variables. In addition to the medical benefits, this analysis demonstrates the economic relevance of the treatment with losartan in DM patients affected by nephropathy.