Giampiero Favato

Economic burden of human papillomavirus-related diseases in Italy

Introduction Human papilloma virus (HPV) genotypes 6, 11, 16, and 18 impose a substantial burden of direct costs on the Italian National Health Service that has never been quantified fully. The main objective of the present study was to address this gap: (1) by estimating the total direct medical costs associated with nine major HPV-related diseases, namely invasive cervical cancer, cervical dysplasia, cancer of the vulva, vagina, anus, penis, and head and neck, anogenital warts, and recurrent respiratory papillomatosis, and (2) by providing an aggregate measure of the total economic burden attributable to HPV 6, 11, 16, and 18 infection. Methods For each of the nine conditions, we used available Italian secondary data to estimate the lifetime cost per case, the number of incident cases of each disease, the total economic burden, and the relative prevalence of HPV types 6, 11, 16, and 18, in order to estimate the aggregate fraction of the total economic burden attributable to HPV infection. Results The total direct costs (expressed in 2011 Euro) associated with the annual incident cases of the nine HPV-related conditions included in the analysis were estimated to be €528.6 million, with a plausible range of €480.1–686.2 million. The fraction attributable to HPV 6, 11, 16, and 18 was €291.0 (range €274.5–315.7 million), accounting for approximately 55% of the total annual burden of HPV-related disease in Italy. Conclusions The results provided a plausible estimate of the significant economic burden imposed by the most prevalent HPV-related diseases on the Italian welfare system. The fraction of the total direct lifetime costs attributable to HPV 6, 11, 16, and 18 infections, and the economic burden of noncervical HPV-related diseases carried by men, were found to be cost drivers relevant to the making of informed decisions about future investments in programmes of HPV prevention.

Anti-HPV vaccination: A review of recent economic data for Italy

The total cost of HPV-related diseases accounts for euro 200-250 million of which euro 210 million is absorbed by the prevention and treatment of precancerous lesions and cervical cancer. Although both available HPV vaccines are below the threshold value for economic convenience (euro 9,569 and euro 26,361 per QALY-gained for the quadrivalent and bivalent vaccines, respectively), at this point in time long-term economic models developed for Italy seem to indicate the quadrivalent vaccine as the most cost-effective option. Recent publications by official bodies, including the World Health Organization and the Supervisory Authority for Public Contracts in Italy, recommend that the decision-making process be based on both the quality of goods and services as well as the best achievable price.

Prevalence of the Prescription of Potentially Interacting Drugs

The use of multiple medications is becoming more common, with a correspondingly increased risk of untoward effects and drug-related morbidity and mortality. We aimed at estimating the prevalence of prescription of relevant potentially interacting drugs and at evaluating possible predictors of potentially interacting drug exposure. We retrospectively analyzed data on prescriptions dispensed from January 2004 to August 2005 to individuals of two Italian regions with a population of almost 2.1 million individuals. We identified 27 pairs of potentially interacting drugs by examining clinical relevance, documentation, and volume of use in Italy. Subjects who received at least one prescription of both drugs were selected. Co-prescribing denotes “two prescriptions in the same day”, and concomitant medication “the prescription of two drugs with overlapping coverage”. A logistic regression analysis was conducted to examine the predictors of potential Drug-Drug Interaction (pDDIs). 957,553 subjects (45.3% of study population) were exposed to at least one of the drugs/classes of the 27 pairs. Overall, pDDIs occurred 2,465,819 times. The highest rates of concomitant prescription and of co-prescription were for ACE inhibitors+NSAIDs (6,253 and 4,621/100,000 plan participants). Considering concomitance, the male/female ratio was <1 in 17/27 pairs (from 0.31 for NSAIDs-ASA+SSRI to 0.74 for omeprazole+clopidogrel). The mean age was lowest for methotrexate pairs (+omeprazole, 59.9 years; +NSAIDs-ASA, 59.1 years) and highest for digoxin+verapamil (75.4 years). In 13/27 pairs, the mean ages were ≥70 years. On average, subjects involved in pDDIs received ≥10 drugs. The odds of exposure were more frequently higher for age ≥65 years, males, and those taking a large number of drugs. A substantial number of clinically important pDDIs were observed, particularly among warfarin users. Awareness of the most prevalent pDDIs could help practitioners in preventing concomitant use, resulting in a better quality of drug prescription and potentially avoiding unwanted side effects.

ASSET (Age/Sex Standardised Estimates of Treatment): A Research Model to Improve the Governance of Prescribing Funds in Italy

Background The primary objective of this study was to make the first step in the modelling of pharmaceutical demand in Italy, by deriving a weighted capitation model to account for demographic differences among general practices. The experimental model was called ASSET (Age/Sex Standardised Estimates of Treatment). Methods and Major Findings Individual prescription costs and demographic data referred to 3,175,691 Italian subjects and were collected directly from three Regional Health Authorities over the 12-month period between October 2004 and September 2005. The mean annual prescription cost per individual was similar for males (196.13 euro) and females (195.12 euro). After 65 years of age, the mean prescribing costs for males were significantly higher than females. On average, costs for a 75-year-old subject would be 12 times the costs for a 25–34 year-old subject if male, 8 times if female. Subjects over 65 years of age (22% of total population) accounted for 56% of total prescribing costs. The weightings explained approximately 90% of the evolution of total prescribing costs, in spite of the pricing and reimbursement turbulences affecting Italy in the 2000–2005 period. The ASSET weightings were able to explain only about 25% of the variation in prescribing costs among individuals. Conclusions If mainly idiosyncratic prescribing by general practitioners causes the unexplained variations, the introduction of capitation-based budgets would gradually move practices with high prescribing costs towards the national average. It is also possible, though, that the unexplained individual variation in prescribing costs is the result of differences in the clinical characteristics or socio-economic conditions of practice populations. If this is the case, capitation-based budgets may lead to unfair distribution of resources. The ASSET age/sex weightings should be used as a guide, not as the ultimate determinant, for an equitable allocation of prescribing resources to regional authorities and general practices.

Novel Health Economic Evaluation of a Vaccination Strategy to Prevent HPV-related Diseases The BEST Study

Background:The development of human papillomavirus (HPV)-related diseases is not understood perfectly and uncertainties associated with commonly utilized probabilistic models must be considered. The study assessed the cost-effectiveness of a quadrivalent-based multicohort HPV vaccination strategy within a Bayesian framework. Methods:A full Bayesian multicohort Markov model was used, in which all unknown quantities were associated with suitable probability distributions reflecting the state of currently available knowledge. These distributions were informed by observed data or expert opinion. The model cycle lasted 1 year, whereas the follow-up time horizon was 90 years. Precancerous cervical lesions, cervical cancers, and anogenital warts were considered as outcomes. Results:The base case scenario (2 cohorts of girls aged 12 and 15 y) and other multicohort vaccination strategies (additional cohorts aged 18 and 25 y) were cost-effective, with a discounted cost per quality-adjusted life-year gained that corresponded to &OV0556;12,013, &OV0556;13,232, and &OV0556;15,890 for vaccination programs based on 2, 3, and 4 cohorts, respectively. With multicohort vaccination strategies, the reduction in the number of HPV-related events occurred earlier (range, 3.8–6.4 y) when compared with a single cohort. The analysis of the expected value of information showed that the results of the model were subject to limited uncertainty (cost per patient=&OV0556;12.6). Conclusions:This methodological approach is designed to incorporate the uncertainty associated with HPV vaccination. Modeling the cost-effectiveness of a multicohort vaccination program with Bayesian statistics confirmed the value for money of quadrivalent-based HPV vaccination. The expected value of information gave the most appropriate and feasible representation of the true value of this program.

Cost-Effectiveness Analysis of Universal Human Papillomavirus Vaccination Using a Dynamic Bayesian Methodology: The BEST II Study

BACKGROUND Human papillomavirus (HPV) plays a role in the development of benign and malign neoplasms in both sexes. The Italian recommendations for HPV vaccines consider only females. The BEST II study (Bayesian modelling to assess the Effectiveness of a vaccination Strategy to prevent HPV-related diseases) evaluates 1) the cost-effectiveness of immunization strategies targeting universal vaccination compared with cervical cancer screening and female-only vaccination and 2) the economic impact of immunization on various HPV-induced diseases. OBJECTIVE The objective of this study was to evaluate whether female-only vaccination or universal vaccination is the most cost-effective intervention against HPV. METHODS We present a dynamic Bayesian Markov model to investigate transmission dynamics in cohorts of females and males in a follow-up period of 55 years. We assumed that quadrivalent vaccination (against HPV 16, 18, 6, and 11) is available for 12-year-old individuals. The model accounts for the progression of subjects across HPV-induced health states (cervical, vaginal, vulvar, anal, penile, and head/neck cancer as well as anogenital warts). The sexual mixing is modeled on the basis of age-, sex-, and sexual behavioral-specific matrices to obtain the dynamic force of infection. RESULTS In comparison to cervical cancer screening, universal vaccination results in an incremental cost-effectiveness ratio of €1,500. When universal immunization is compared with female-only vaccination, it is cost-effective with an incremental cost-effectiveness ratio of €11,600. Probabilistic sensitivity analysis shows a relatively large amount of parameter uncertainty, which interestingly has, however, no substantial impact on the decision-making process. The intervention being assessed seems to be associated with an attractive cost-effectiveness profile. CONCLUSIONS Universal HPV vaccination is found to be a cost-effective choice when compared with either cervical cancer screening or female-only vaccination within the Italian context.

Using scenario thinking to make real options relevant to managers: a case illustration

This paper argues the advantages of Real Options thinking and by means of examples, exhibits the types of decision-making calculations that are distinctive to Real Options. However, in the process of clarifying the application of Real Options analysis to real decision making, a strong dependency upon scenario thinking is established. The value to decision makers of Real Options depends crucially on the substance and use of the scenarios on which it rests. The distinctive contribution of this paper consists in substantiating this view. By forging a critical link between Real Options analysis and scenario thinking, this paper illustrates how the beneficial application of Real Options to decision making brings it down from the esoteric heights of mathematics, converts it into a technique readily accessible to managers and qualifies it for inclusion in the curriculum of management education. Two cases drawn from personal experience are used to illustrate the approach recommended by the authors.

Governance of preventive Health Intervention and On time Verification of its Efficiency: the GIOVE Study

Objectives The GIOVE Study was aimed to the achievement of allocative efficiency of the budget allocated to the prevention of human papillomavirus (HPV)-induced diseases. An ex-ante determination of the most efficient allocation of resources between screening and multicohort quadrivalent immunisation programmes was followed by the ex-post assessment of the allocative efficiency actually achieved after a 12-month period. Design A bound optimisation model was developed to determine the ex-ante allocative efficiency of resources. The alternatives compared were the screening programme alone and the quadrivalent immunisation with access to screening. A sensitivity analysis was carried out to assess the uncertainty associated with the main inputs of the model. Subsequently, a cohort of girls with a complete recorded vaccination history were enrolled in an observational retrospective study for 18 months to ensure full compliance with the recommended schedule of vaccination (0, 2, 6 months) within a 12-month time horizon. Setting Basilicata region, in the south of Italy. Participants 12 848 girls aged 12, 15, 18 or 25 years. Intervention Immunisation with quadrivalent anti-HPV vaccine. Outcome measures The vaccination coverage rate was considered to be the indicator of the best achievable benefit, given the budgetary constraints. Results Assuming a vaccine price of €100 per dose, a vaccination coverage rate of 59.6% was required for the most effective allocation of resources. The optimal rate of coverage was initially in favour of the multicohort strategy of vaccination against HPV (72.8%±2%). When the price paid for the quadrivalent vaccine dropped to €85 per dose, the most efficient coverage rate (69.5%) shifted closer to the immunisation rate actually achieved during the 12-month observation period. Conclusions The bound optimisation model demonstrated to be a useful approach to the ex-ante allocation and the ex-post assessment of the resources allocated to the implementation of a multicohort quadrivalent anti-HPV vaccination programme.

Art as an Alternative Investment Asset

The paper constitutes a discussion of the trend around the rise of art as an alternative investment. With financial markets in turmoil, art as an alternative asset class is being incorporated into portfolios in the interest of diversification. Arts low correlation with the equities market and desirable risk and reward ratio, as price appreciation defies all logic, makes it an attractive investment. The volatility, irrationality and illiquidity of the art market make it hard to compare to more conventional investments. The paper will look at how investors are treating art as an asset class and how art compares to more traditional assets such as equities and bonds.

Evaluation of the economic impact produced by the prevention of events induced by the HPV 6-11 virus types contained in the quadrivalent vaccine

Although the integration of the fragmentary data concerning the total expenses borne for the early diagnosis and the treatment of HPV-induced pathologies is problematic, it is possible to break down the total burden of HPV-induced events into the leading determinants of cost. By entering the results obtained from several published studies into a model specifically designed to evaluate the economic effectiveness of the implementation of a multi-cohort vaccination strategy in Italy, it is possible to estimate the effect of the quadrivalent vaccine in terms of number of prevented events and the potential cost reduction. The quadrivalent vaccine should determine a significant cost-saving of 68.6%, corresponding to approximately 70 million euros.