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Objective: The main objective of this study was to evaluate the potential role of efficacy data and other information available at the time of price and reimbursement (P&R) decision-making process within the definition of oncology treatment costs in Italy.Methods: The study included all P&R dossiers submitted to the Italian Medicines Agency between July 2015 and December 2017. It prospectively collected the data of the P&R process starting from dossier submission up to the Italian Health Service reimbursement decision. The cost of treatment per patient was estimated using both the list price ("gross cost") and the confidential net price ("net cost") of drug packages and applied to the median duration of treatment. A 2-sample stage Heckman decomposition model was used to evaluate the potential role of efficacy data and other information available at the time of P&R decision making on the gross and net cost.Results: A total of 37 oncology drugs related to 58 therapeutic indications were analyzed. The multivariate model showed that the variation of progression-free survival is the only variable predictor statistically associated with treatment cost, but this effect was observed only when confidential net prices were used (P=.026).Conclusions: Considering the perspective of a developed country having a public healthcare service with a central reimbursement negotiation is determined a relevant reduction in the treatment cost purchased by public payers. This is a useful approach to guarantee the affordability of innovative oncology drugs and to contain public expenditures on healthcare. Furthermore, the negotiation of confidential discounts and agreement clauses in managed entry agreements seemed to reward oncology drugs displaying an added therapeutic benefit. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Purpose: A complete economic evaluation requires accurate data concerning the resources used, outcomes, and utilities (patient's preferences) to properly value the cost utility of human papillomavirus (HPV) vaccination strategies. This study was designed to measure the utility loss in health states affected by a broad range of HPV-induced pathologies in both sexes in Italy. As a secondary objective, risk factors influencing the viral transmission and development of HPV infections were also investigated. Methods: Patients with a diagnosis of several HPV induced pathologies including atypical squamous cells of undetermined significance (ASC-US), cervical intraepithelial neoplasia (CIN), cervical and anal-colorectal cancer, head and neck squamous cell carcinoma (HNSCC) and anogenital warts (AWs) were evaluated. Utilities, quality of life, and risk factors were elicited using a standardized and computer-guided administration of time trade-off, European Quality of Life 5 Dimensions (EQ-5D), 3 levels, and risk factor questionnaires. Utilities were measured at 6 clinical research centers across Italy. A group of healthy subjects was used as a control. A mean number of 20 healthy subjects was used as a control for each pathology group. Findings: Overall, 600 respondents were eligible for analysis: 465 patients (mean [SD] age, 44.0 [16.3] years) and 135 controls (mean [SD] age, 44.0 [13.2] years). With the exception of anal and HNSCC cancer, no statistically significant differences were observed between case and control groups, in terms of either age or quality of life at the time of interview. The patients' perception of their health condition at baseline was equal to an EQ-5D score of 0.87 (0.22). The mean (SD) value of utilities associated with the HPV-induced pathologies corresponded to 0.83 (0.24), 0.78 (0.27), 0.83 (0.22), 0.81 (0.27), 0.58 (0.31), 0.51 (0.26), and 0.69 (0.30) for ASC-US, AWs, CIN 1 (mild), CIN 2-3 (moderate to severe), cervical cancer, anal cancer and HNSCC, respectively. Utility lost due to AWs was significantly higher in females compared with males (0.71 [0.29] vs 0.83 [0.25]; P= 0.018). Having 45 sexual partners increased the risk of acquiring HPV induced infections as much as 2.52-fold (P= 0.004), whereas for smoking or the age at start of sexual activity younger than 18 years, the risk increased by ~1.62-fold (P= 0.034). High levels of education were associated with a statistically significant protective effect (P < 0.001). Implications: Risk factors and utilities elicited in this study can be used as part of future economic assessments of other HPV vaccination strategies, including an immunization program for preadolescents of both sexes in Italy. [ABSTRACT FROM AUTHOR]

Background: A large number of economic evaluations have already confirmed the cost-effectiveness of different human papillomavirus (HPV) vaccination strategies. Standard analyses might not capture the full economic value of novel vaccination programs because the cost-effectiveness paradigm fails to take into account the value of active management. Management decisions can be seen as real options, a term used to refer to the application of option pricing theory to the valuation of investments in nonfinancial assets in which much of the value is attributable to flexibility and learning over time. OBJECTIVE: The aim of this article was to discuss the potential advantages shown by using the payoff method in the valuation of the cost-effectiveness of competing HPV immunization programs. METHODS: This was the first study, to the best of our knowledge, to use the payoff method to determine the real option values of 4 different HPV vaccination strategies targeting female subjects aged 12, 15, 18, and 25 years. The payoff method derives the real option value from the triangular payoff distribution of the project's net present value, which is treated as a triangular fuzzy number. To inform the real option model, cost-effectiveness data were derived from an empirically calibrated Bayesian model designed to assess the cost-effectiveness of a multicohort HPV vaccination strategy in the context of the current cervical cancer screening program in Italy. A net health benefit approach was used to calculate the expected fuzzy net present value for each of the 4 vaccination strategies evaluated. RESULTS: Costs per quality-adjusted life-year gained seemed to be related to the number of cohorts targeted: a single cohort of girls aged 12 years (€10,955 [95% CI, -1,021 to 28,212]) revealed the lowest cost among the 4 alternative strategies evaluated. The real option valuation challenged the cost-effectiveness dominance of a single cohort of 12-year-old girls. The simultaneous vaccination of 2 cohorts of girls aged 12 and 15 years yielded a real option value (€17,723) equivalent to that attributed to a single cohort of 12-year-old girls (€17,460). CONCLUSIONS: The payoff method showed distinctive advantages in the valuation of the cost-effectiveness of competing health care interventions, essentially determined by the replacement of the nonfuzzy numbers that are commonly used in cost-effectiveness analysis models, with fuzzy numbers as an input to inform the real option pricing method. The real option approach to value uncertainty makes policy making in health care an evolutionary process and creates a new "space" for decision-making choices. [ABSTRACT FROM AUTHOR]

Abstract: Background: The economic evaluation of any human papillomavirus (HPV) vaccination strategy requires the measurement of clinical benefits (quality-adjusted life-years [QALY]) gained to reflect both the increase in life expectancy and the economic benefits associated with an effective intervention. Objective: The purpose of this pilot study was to investigate the feasibility of a standardized time trade-off (TTO) procedure to quantify utilities loss in health states affected by HPV-induced pathologies in Italy. Methods: This multicenter, retrospective, observational, cross-sectional study was designed to elicit data on utilities in a cohort of women with a histologically confirmed diagnosis of high-grade cervical intraepithelial neoplasias (CIN2-3). An algorithm for the computerized administration of a TTO questionnaire was developed for the standardized elicitation of data on health utilities in CIN2-3, anogenital warts, and invasive cervical cancer. The European Quality of Life–5 Dimensions (EQ-5D) questionnaire was used to assess the respondents'' baseline perception of their health conditions. The correlation between utilities and age, time from conization to questionnaire administration, and EQ-5D score, was tested using the Spearman rank correlation coefficient (ρ) as a measure of validity. Results: Of 42 enrolled patients, 36 responded (85.7%) (mean [SD] age, 37.2 [9.0] years). The women''s perception of their health state was high (mean [SD] EQ-5D score, 0.93 [0.10]). The mean utility values were 0.73 (0.22), 0.71 (0.35), and 0.02 (0.08) for CIN2-3, anogenital warts, and invasive cervical cancer, respectively. Based on ρ values, none of the 3 HPV-induced pathologies considered was significantly correlated with utility. Nonsignificant variability was found among utilities elicited for anogenital warts (range, 0.54 [0.47] to 0.79 [0.27]); this variability was a limitation of this pilot study and was likely the result of the limited sample size. Conclusions: Based on the findings from this pilot study, a TTO standardized procedure is expected to be feasible and appropriate for assessing utilities in patients affected by HPV-related diseases and for cost-effectiveness analyses of cervical cancer prevention in Italy. [ABSTRACT FROM AUTHOR]

Background SOX2 is one of the pluripotency transcription factors expressed by stem cells, playing a central role in maintenance of stemness and overexpressed in a variety of solid tumours. In breast cancer, SOX2 expression has mainly been reported in the basal-like subtype. We evaluated a heterogenous group of breast cancer tissues to determine whether the expression of SOX2 and other pluripotency transcription factors correlated with clinicopathological factors and recurrence. Methods 140 primary invasive breast cancer specimens were collected. mRNA expression for SOX2, OCT4, NANOG, and GDF3 genes was assessed by RT-PCR. Immunohistochemistry was done for SOX2. Correlations with molecular subtypes, menopausal status, grading, ER, PR, ki67 (⩽20%), HER2, T-size, and node status were evaluated. Association of SOX2 expression and disease-free survival was estimated by univariate and multivariate analysis ( p ⩽ 0.05). Findings In 117 samples assessable by RT-PCR we found the following correlations: NANOG and grade 2, GDF3 and node-negative, SOX2 and higher ki67 ( p = 0.019, p = 0.029, p = 0.035, respectively). At univariate analysis of disease-free survival, SOX2 expression (hazard ratio (HR) 2.36; p = 0.002), ki67 (HR 2.19; p = 0.028), T-size ⩾1 (HR 2.06; p = 2.011), node-status (HR 2.21; p = 0.014); ER/PR (HR 0.58/HR 0.59, p = 0.065/ p = 0.068) were statistically significant. At multivariate analysis, SOX2 (HR 2.99; 95% confidence interval (CI) 1.41–6.30; p = 0.004), node-status (HR 2.44; 95% CI 1.25–4.76; p = 0.009), and T-size ⩾1 (HR 1.77; 95% CI 0.99–3.13; p = 0.051) were associated with increased risk of recurrence. An earlier recurrence was observed in SOX2 + (median 34.9 months; 95% CI 7.5–62.2) than SOX2- patients (median: 60.3 months; 95% CI 32.6–88.1; p = 0.017); overall survival was shorter in SOX2 + patients than in those who were SOX-(68.2 months, 95% CI 63.7–151.4 versus 145.3 months, 95% CI: 80.5–210.2) although this was not significant ( p = 0.104). IHC showed SOX2 protein expression in all of 11 samples; no expression was noted in 20 randomly selected SOX2- samples. Interpretation Our analysis confirms that expression of pluripotency transcription factors correlates with specific clinicopathological factors (grade, node-status, and ki67). SOX2 expression was associated with an increased risk of recurrence, irrespective of other clinicopathological factors. [ABSTRACT FROM AUTHOR]