Human papillomavirus vaccination: what is the best choice? A comparison of 16 strategies by means of a decisional model.

Some European countries decided to include human papillomavirus (HPV) vaccines in national immunization schedules. In order to help decision makers choose the best vaccination policy for females, a decisional model has been developed. The study was performed from the National Health Service perspective. Several hypotheses of multi-cohort vaccination policies were compared. 'Potentially avoidable infections' were chosen as the outcome. The model envisioned a short-term scenario (2008-2011). The best policy was that of vaccinating 12-year-olds and, a year later, those aged 14-16 years; the most expensive strategy was that of vaccinating 12-year-old females and, after 1 year, vaccinating those aged 15, 18 and 25 years. The sensitivity analysis showed that coverage rate has a great effect on the cost of avoidable infections. The study offers stake-holders an important datum-point for the choice of the best HPV policy vaccination in the short term. Indeed, it could generate interesting savings for the National Health Service and a rapid HPV immunization of young girls.

GOLD severity stratification and risk of hospitalisation for COPD exacerbations.

BACKGROUND AND AIM: The Italian Costs for Exacerbations in COPD ("ICE") study, following a pharmacoeconomic assessment of costs due to COPD exacerbations (primary endpoint), aimed also at evaluating (secondary endpoint) which clinical factors, among those considered for cost-analysis, may, at follow up, present a risk of new exacerbations and re-admission to hospital. MATERIALS AND METHODS: A prospective, multicentre study was carried out on COPD patients admitted to 25 Hospital Centres as a result of an exacerbation from October-December 2002. Following discharge, a 6-month follow-up was performed in each patient via three bi-monthly telephone interviews with a questionnaire administered by an investigator clinician. RESULTS: 570 patients were eligible for data processing, mean age 70.6 years (+/- 9.5 standard deviation, SD), males 69.2%. According to GOLD, severity stratification was as follows: moderate 36.4%; severe 31.3%; very severe 32.3%. 282 patients experienced at least one exacerbation at follow up, 42% of exacerbations requiring hospitalisation. No significant association was seen between exacerbations and GOLD stage or co-morbidities or treatments except LTOT. Conversely, COPD functional severity influenced hospitalisations very significantly, with relative risks 2.6 (95% Confidence Interval, CI 1.8-3.8) and 2.0 (CI 1.3-2.8) (GOLD very severe versus moderate and severe, respectively), and 1.3 (CI 0.85-2.1) (GOLD severe versus moderate). Hospitalisations were also significantly associated with treatments denoting more severe conditions (oral corticosteroids, oral theophylline, and LTOT). CONCLUSIONS: Severity stratification of COPD patients according to respiratory function classes as outlined in GOLD guidelines and need for LTOT are confirmed as important predictors of hospitalisation for an exacerbation.

Costs and quality of life of multiple sclerosis in Italy.

This cost-of-illness analysis based on information from 921 patients in Italy is part of a Europe-wide cost-of-illness study in multiple sclerosis (MS). The objective was to analyze the costs and quality of life (QOL) related to the level of disease severity and progression. Patients registered with the Italian MS patient organization were asked to participate in a mail survey, and 31% responded. The questionnaire asked for details on the disease (type of disease, relapses, level of functional disability), information on all medical and non-medical resource consumption, and informal care and work capacity (sick leave and early retirement). In addition, patients were asked about their current QOL (in the form of utility) and the level of fatigue. The mean age of respondents was 46 years, and 8.5% were 65 years or older. As many as 20% of patients had severe disease (Expanded Disability Status Scale [EDSS] score of > or =7), 47% had moderate disease (EDSS score of 4-6.5) and only 31% had mild disease (EDSS score of 0-3). Thus, the mean EDSS score in the sample was 4.6 (median 5.0), with a utility of 0.53 (range: 0 = death to 1 = full health) and a fatigue level of 6.4 (range: 1 = not tired to 10 = extremely tired). Costs and utility are highly correlated with disease severity. Workforce participation decreases from approximately 80% in early disease to less than 10% in the very late stages. Total costs increase fivefold between an EDSS score of 0-1 and a score of 7. Health-care costs, however, show a limited increase with worsening disease--hospitalization increases from euro 800 per patient to euro 3200, and ambulatory care increases from euro 900 to euro 1500. Productivity losses, on the other hand, increase by a factor of 12, while informal care increases from euro 500 at an EDSS score of 0-1 to nearly euro 25 000 at an EDSS score of 7, and euro 39 000 at an EDSS score of 8-9. Hence, total mean costs per patient are determined essentially by the distribution of the severity levels in the sample, increasing from euro 12 000 at an EDSS score of 0-1 to euro 57 000 at an EDSS score of 7, and euro 71 000 at an EDSS score of 8-9. The same is true for utility, which decreases from 0.80 to 0.06 as the disease becomes severe. However, the utility loss compared to the age- and gender-matched general population is high at all levels of the disease, leading to an estimated annual loss of 0.3 quality-adjusted life year (QALY) per patient. Relapses for patients with an EDSS score of <5 are associated with a cost of approximately euro 4000 and a utility loss of 0.18 during the quarter in which they occur.

Proton pump inhibitors in acute treatment of reflux oesophagitis : a cost-effectiveness analysis.

BACKGROUND AND AIM: Gastro-oesophageal reflux disease is a common medical problem that places a significant financial burden on outpatient pharmaceutical expenditure. A substantial proportion of this expenditure can be attributed to the use of proton pump inhibitors (PPIs). The aim of this analysis was to evaluate the cost-effectiveness of PPIs currently licensed in Italy in the acute treatment of reflux oesophagitis. METHODS: A decision analysis model that simulated the sequential management of reflux oesophagitis over the course of 8 weeks was constructed. Healing rates were derived from a published meta-analysis of PPIs for reflux oesophagitis. Costs of PPIs were based on retail prices in Italy, endoscopies and specialist (outpatient) visits were costed on the basis of public tariffs, and opportunity costs were calculated for general practitioner visits. The clinical effectiveness of a PPI was measured in terms of the proportion of patients healed at 8 weeks. An incremental cost-effectiveness analysis was performed, using omeprazole, the recognised 'gold standard' PPI in Italy, as the common comparator. The perspective of the analysis was the Italian National Health System (NHS). A sensitivity analysis was conducted in which the key parameters in the model were varied according to a Monte Carlo simulation of 1000 patients. RESULTS: Esomeprazole 40 mg/day was a dominant treatment option compared with omeprazole 20 mg/day (88.8% patients healed vs 82.2%, respectively; total treatment cost euro164.85 vs euro169.56, respectively (year of costing, 2002). Furthermore, on the basis of the 95% CIs generated by the Monte Carlo simulation, esomeprazole 40 mg/day appears to be more cost-effective than both lansoprazole 30 mg/day and pantoprazole 40 mg/day. CONCLUSIONS: Esomeprazole 40 mg/day can be considered a cost-effective treatment option for the acute treatment of reflux oesophagitis in Italy.

Utilisation Pattern of Nonspecific Nonsteroidal Anti-Inflammatory Drugs and COX-2 Inhibitors in a Local Health Service Unit in Northeast Italy.

BACKGROUND AND OBJECTIVE: Nonsteroidal anti-inflammatory drugs (NSAIDs) are prescribed widely in Italy. They include nonspecific NSAIDs (NS-NSAIDs) and the newly marketed cyclo-oxygenase (COX)-2 specific inhibitors (COXIBs) celecoxib and rofecoxib. The objective of this study was to describe the prescribing patterns for NS-NSAIDs and COXIBs in a local Italian area, analysing an administrative database. PATIENTS AND METHODS: We extracted from the database information on subjects who had received at least one reimbursed prescription of an NSAID during the period between 1 January 2001 and 31 December 2001, including age, sex, patient identification code, Anatomical Therapeutic Chemical (ATC) classification system code, strength, formulation, number of packs prescribed, prescription date, and prescription of gastroprotective agents (GPAs) on the same day as the prescription of the NSAID. On the basis of the type of NSAID received, we divided the patients into five cohorts: oral NS-NSAIDs only during the observed year, injectable NS-NSAIDs only, celecoxib only, rofecoxib only, and a combination. For descriptive purposes, we defined three age groups: <40 years, 40-64 years, and >64 years. The duration of exposure to NSAID therapy was calculated using the most commonly prescribed dose for the different drugs. Subjects receiving >/=30 doses per year were defined as "regular users". Analyses included mean age, mean duration of exposure, percentage of regular users, and percentage of GPAs co-prescribed in the different cohorts. RESULTS: NSAIDs were prescribed to 62 059 subjects from a resident population of 365 321 inhabitants; 43.8% received oral NS-NSAIDs only, 22.6% injectable NS-NSAIDs only, 7.2% celecoxib only, 5.2% rofecoxib only, and 22% different regimens of different types of NSAIDs. The mean duration of treatment increased with age in all cohorts; the mean age was 56 years in the NS-NSAID cohort, 61 years in the celecoxib cohort, and 62 years in the rofecoxib cohort (p = 0.01, COXIBs vs NS-NSAIDs). The mean duration of therapy was 11.4 days/year for injectable NS-NSAIDs, 43.8 days/year for rofecoxib, 50.5 days/year for oral NS-NSAIDs, and 53.7 days/year for celecoxib. Fifty-four percent of subjects in the oral NS-NSAID cohort were regular users versus 64% in the rofecoxib and 70% in the celecoxib groups (p = 0.001, COXIBs vs NS-NSAIDs). Co-prescription with GPAs was 9.5% for NS-NSAIDs, 8.4% for rofecoxib, and 7.7% for celecoxib. CONCLUSIONS: Analysis of an administrative database in Italy showed a trend suggesting that COXIBs are prescribed to an older population and for a longer period of time than NS-NSAIDs, and that their use is less frequently associated with GPAs.

Cost-benefit evaluation of influenza vaccination in the elderly in the Italian region of Liguria.

Influenza causes considerable morbidity and mortality and the damage to public health can be considerable. The most effective measures available for the prevention of influenza is vaccination. In most industrialised countries the objective of vaccination is to limit the disease among individuals at risk, especially the elderly. During the winter of 2000/2001, General Practitioners (GPs) monitored 14,818 elderly individuals. The objective was to evaluate the weekly incidence of the disease. Furthermore, we carried out a prospective study on 512 elderly individuals, arranged according to vaccination (304 vaccinated and 208 non-vaccinated), with the main objective of assessing the costs of the disease and the efficacy of vaccination. Finally, in order to assess the percentage of vaccinated elderly individuals, we carried out a telephone survey on 500 subjects. Our clinical surveillance study enabled us to establish that morbidity was particularly low in elderly individuals.The results of the prospective study allowed us to estimate the cost-benefit ratio at 8.22, with a net saving of 110.20 Euros for each vaccinated subject. We were also able to establish that the vaccine coverage among elderly individuals was 63%. Our study, though carried out during a low epidemic year, confirms the economic advantage of vaccination in the elderly.

Assessing the impact of complications on the costs of Type II diabetes.

AIMS/HYPOTHESIS: 'The Cost of Diabetes in Europe - Type II (CODE-2) study' provides the first coordinated attempt to assess the total costs of managing people with Type II (non-insulin-dependent) diabetes mellitus in Europe. Type II diabetes is associated with a number of serious long-term complications, which are a major cause of morbidity, hospitalisation and mortality in diabetic patients. METHODS: Patients were divided into four broad categories defining their complication status in terms of no complications, one or more microvascular complications, one or more macrovascular complications or one or more of each microvascular and macrovascular complication. The prevalence of complications and associated costs were assessed retrospectively for 6 months. RESULTS: In total, 72% of patients in the CODE-2 study had at least one complication, with 19% having microvascular only, 10% having macrovascular only and 24% of the total having both microvascular and macrovascular complications. Of patients with microvascular complications, 28% had neuropathy, 20% renal damage, 20% retinopathy and 6.5% required treatment for eye complications. Among the patients with macrovascular complications, 18% had peripheral vascular disease, 17% angina, 12% heart failure and 9% had myocardial infarction. Percutaneous transluminal coronary angioplasty, coronary artery bypass graft or stroke occurred in 3%, 4% and 5% of the patients, respectively. In patients with both microvascular and macrovascular complications, the total cost of management was increased by up to 250% compared to those without complications. CONCLUSION/INTERPRETATION: Complications have a substantial impact on the costs of managing Type II diabetes. This study has confirmed that the prevention of diabetic complications will not only benefit patients, but potentially reduce overall healthcare expenditure.

Assessing the impact of complications on the costs of Type II diabetes.

AIMS/HYPOTHESIS: 'The Cost of Diabetes in Europe-Type II (CODE-2) study' provides the first coordinated attempt to assess the total costs of managing people with Type II (non-insulin-dependent) diabetes mellitus in Europe. Type II diabetes is associated with a number of serious long-term complications, which are a major cause of morbidity, hospitalisation and mortality in diabetic patients. METHODS: Patients were divided into four broad categories defining their complication status in terms of no complications, one or more microvascular complications, one or more macrovascular complications or one or more of each microvascular and macrovascular complication. The prevalence of complications and associated costs were assessed retrospectively for 6 months. RESULTS: In total, 72% of patients in the CODE-2 study had at least one complication, with 19% having microvascular only, 10% having macrovascular only and 24% of the total having both microvascular and macrovascular complications. Of patients with microvascular complications, 28% had neuropathy, 20% renal damage, 20% retinopathy and 6.5% required treatment for eye complications. Among the patients with macrovascular complications, 18% had peripheral vascular disease, 17% angina, 12% heart failure and 9% had myocardial infarction. Percutaneous transluminal coronary angioplasty, coronary artery bypass graft or stroke occurred in 3%, 4% and 5% of the patients, respectively. In patients with both microvascular and macrovascular complications, the total cost of management was increased by up to 250% compared to those without complications. CONCLUSION/INTERPRETATION: Complications have a substantial impact on the costs of managing Type II diabetes. This study has confirmed that the prevention of diabetic complications will not only benefit patients, but potentially reduce overall healthcare expenditure.

Quality of life and utility in patients with non-small cell lung cancer. Quality-of-life Study Group of the Master 2 Project in Pharmacoeconomics.

BACKGROUND: Although several studies have determined quality of life in patients with lung cancer, there is still little information about the use of generic questionnaires [e.g. the 36-item Short Form health survey (SF-36)] and utility questionnaires [e.g. the EuroQOL instrument (EQ-5D)] in this disease. OBJECTIVES: To (i) measure quality of life and utility in patients with non-small cell lung cancer (NSCLC) using the SF-36 and the EuroQOL questionnaires; (ii) to evaluate the impact of some clinical variables on quality of life and utility; (iii) to assess the correlation between the measurements produced by the 2 questionnaires. STUDY DESIGN: Cross-sectional study. PARTICIPANTS: 95 patients from 15 Italian hospitals with NSCLC (93% male, mean age 62 years) completed both questionnaires. RESULTS: The mean scores for the 8 domains of the SF-36 ranged from 20.8 (physical role) to 63.0 (social functioning). The mean physical and mental summed scores of the SF-36 were 36.8 [standard deviation (SD) 9.8] and 43.0 (SD 11.5), respectively. The EuroQOL mean score was 0.58 (SD 0.32) in the self-classifier (SC) version and 0.58 (SD 0.20) in the visual analogue scale (VAS) version. Among the clinical variables that affected quality of life and utility, the presence of metastasis had the greatest impact: patients with metastasis had statistically significantly lower scores for 2 domains of the SF-36 (physical functioning, p = 0.009; bodily pain, p = 0.016), for the physical component summed score of the SF-36 (p = 0.015) and for both utility estimates (EuroQOL-SC, p = 0.027; EuroQOL-VAS, p = 0.038) than patients without metastasis. Both the SC and VAS EuroQOL scores showed a statistically significant correlation with each of the 8 domains of the SF-36. The scores for both the SF-36 and the EuroQOL in patients with NSCLC were considerably worse (relative differences ranging from -8 to -73%) than the corresponding values (normative data) previously reported for healthy individuals. CONCLUSIONS: Our study quantified the degree to which quality of life is impaired in patients with NSCLC, showed that the presence of metastasis had an important role, and indicated a strong correlation between the measurements produced by the 2 questionnaires. The EuroQOL measurements obtained from these patients will aid evaluation of the cost-utility ratio for NSCLC therapies.

Epidemiology and cost analysis of varicella in Italy: results of a sentinel study in the pediatric practice. Italian Sentinel Group on Pediatric Infectious Diseases.

BACKGROUND: Describing the epidemiology of varicella is relevant to the development of specific prevention strategies and to building up of economic models evaluating the cost:efficiency ratios of these strategies. AIM: Our study was designed to describe the epidemiology of chickenpox among Italian children and to assess the resulting economic and health burden on the country. METHODS: Thirty-nine Italian pediatricians participated in a sentinel network on pediatric infectious diseases representing a total pediatric population of 30 168 children. Each case of varicella observed from January through December, 1997, was recorded. Economic analysis was conducted from the societal point of view. All costs were broken down into two groups: direct and indirect costs. RESULTS: A total of 1599 cases of varicella were reported among children 0 to 14 years old. There were 1266 primary cases (mean age, 4.5 +/- 2 years) and 333 secondary cases (mean age, 3.6 +/- 3.2 years). The global incidence of chickenpox was 51.01/1000/year. Complications were seen in 56 cases (3.5%). Drugs were prescribed in 672 cases. A group of adults (364 susceptible and 193 with uncertain status) were exposed to primary cases. Seventy (12.5%) were eventually infected among whom there were 4 pregnant women. For pediatric patients an average cost of $146.90 (250 400 lire) was estimated; this is largely accounted for by indirect costs. CONCLUSIONS: The epidemiology of varicella in Italy is consistent with that found in previous studies in industrialized countries. Severe complications did not occur in our population. We believe that the health arguments in favor of universal vaccination of children > 18 months of age do not differ in our own country from those of other industrialized nations. Our data could now be incorporated into pharmacoeconomic models to establish cost-efficient strategies for Italy.

Resource costing for multinational neurologic clinical trials: methods and results.

We present the results of a multinational resource costing study for a prospective economic evaluation of a new medical technology for treatment of subarachnoid hemorrhage within a clinical trial. The study describes a framework for the collection and analysis of international resource cost data that can contribute to a consistent and accurate intercountry estimation of cost. Of the 15 countries that participated in the clinical trial, we collected cost information in the following seven: Australia, France, Germany, the UK, Italy, Spain, and Sweden. The collection of cost data in these countries was structured through the use of worksheets to provide accurate and efficient cost reporting. We converted total average costs to average variable costs and then aggregated the data to develop study unit costs. When unit costs were unavailable, we developed an index table, based on a market-basket approach, to estimate unit costs. To estimate the cost of a given procedure, the market-basket estimation process required that cost information be available for at least one country. When cost information was unavailable in all countries for a given procedure, we estimated costs using a method based on physician-work and practice-expense resource-based relative value units. Finally, we converted study unit costs to a common currency using purchasing power parity measures. Through this costing exercise we developed a set of unit costs for patient services and per diem hospital services. We conclude by discussing the implications of our costing exercise and suggest guidelines to facilitate more effective multinational costing exercises.

Cost of an outbreak of hepatitis A in Puglia, Italy.

In total, 5889 cases of hepatitis A virus infection were reported during an outbreak in Puglia, a region of Southern Italy, in 1996. The primary cause of the outbreak was consumption of contaminated food (raw shellfish, vegetables, etc.), with a contributory risk factor of person-to-person transmission. A detailed questionnaire was completed by 250 randomly selected patients to obtain information sufficient to calculate the direct and indirect costs of the outbreak for the individual patient, the National Health Service (NHS) and society as a whole. A conversion rate of $US1 = 1530 Italian lire (L) has been used throughout the study since this was the average exchange rate in 1996. For the individual patient with hepatitis A virus infection, the mean cost was L1.013 million ($US662), which was equivalent to 6.6% of the mean annual income of the employed patients. The total cost of the outbreak to the NHS was L23.98 billion ($US15.67 million), which was equivalent to 0.4% of the total public health expenditure in the region in 1996. The total cost of the outbreak to society (individual patient, NHS and third parties combined) was L37.406 billion ($US24.45 million), corresponding to 0.04% of the gross domestic product of the entire region in 1996, with a mean cost per patient of L6.35 million ($US4150) from a societal perspective. The majority of patients (86.3%) were 11 to 30 years of age, reflecting the increasing susceptibility of younger patients to hepatitis A virus infection in recent decades. These economic and demographic data provide important information for the evaluation of preventive strategies including public education, sanitation and immunisation, so as to optimise the use of local health resources.

A multinational economic evaluation of rhDNase in the treatment of cystic fibrosis.

Economic evaluations of pharmaceuticals are increasingly being conducted in conjunction with randomized phase III clinical trials to meet the demand for pharmacoeconomic data when new products are launched. While the need for such data is often global, the trials in which relevant information may be collected are often conducted in only one or a limited number of countries. A critical issue is how data from pivotal clinical trials in one setting can serve as the basis for pharmacoeconomic evaluations in others. We address this issue and report on four economic evaluations that we undertook in conjunction with a recent U.S. phase III clinical trial of recombinant human deoxyribonuclease (rhDNase), which is used to improve pulmonary function in patients with cystic fibrosis (CF). The objective of these evaluations was to estimate the potential impact of rhDNase therapy in France, Germany, Italy, and the United Kingdom on the direct costs of medical care for the treatment of respiratory tract infections (RTIs) in patients with CF. Analyses of economic impact were undertaken both with and without adjustment for differences in practice patterns between the United States and the countries of interest. Our findings suggest that rhDNase therapy may reduce the cost of RTI-related care by between US$600 and US$1,100 over a 24-week period; the cost of rhDNase is not included in these figures, as a price was unavailable when our analyses were undertaken. Despite methodologic challenges, economic evaluations that meet the information needs of decision makers in diverse countries can nonetheless be undertaken in conjunction with phase III clinical trials.

Economic evaluation of drug prescription monitoring systems in the extra-hospital environment.

Drugs expenditure accounts for a significant and rising share of public health expenditure (from 14% in 1980 it has now reached 17% approximately). Many efforts have been made to contain its expansion through tickets (co-payments), formularies, price policies, etc., but overall results have been unsatisfactory. The main cause for this failure may be found in the approach adopted, virtually excluding the evaluation of rational use of drugs. Economic evaluation of drug prescription, comparing cost per DDD, assessing both cost/effectiveness ratios and the monitoring system's efficiency, may contribute to a better control of drug expenditure.

[Current problems in assessing drug prices]. / Problemi atuali in tema di fissazione del prezzo dei farmaci.

Two reasons provide historical justification for controlling drug prices: safeguarding the consumer and safeguarding public demand. Due to the increased presence of the "third payer" in public health systems this second reason has become more important. Nevertheless, over the last decade, a third purpose has attached to public control of prices: promotion of drug manufacturers economic development. The justification offered for this is that development of pharmaceutical companies contributes to the economic growth of the host country by creating employment, exports and research activity. The situations in Germany, Great Britain and United States are often cited in support of this thesis. As a model for price policy in Italy, however, it has not been successful. The rapid growth of prices in fact has not created greater employment and the foreign exchange deficit has risen rapidly. In other words the growing cost of drugs to the National Health Service has not produced hoped-for economic benefits. It would therefore be opportune to modify the mechanisms of price control by seeking a better balance in the interests involved (safeguarding public demand versus manufacturers economic growth). Methodologies available point to the evaluation of the therapeutic utility of a drug as a useful tool for this purpose. By this method the price of a new drug may only be higher than that of a drug already on the market if its therapeutic utility (which does not coincide only with clinical effectiveness) is greater. Appropriate evaluation techniques of benefits deriving from a new drug (cost-effectiveness and cost-utility) do exist and can be taken into consideration in a new method of calculating drug price.