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Metformin is an antidiabetic drug; used to treat type II diabetes mellitus, metformin associated lactic acidosis has an incidence of 2-9 cases / 100,000 patients / year with high mortality (30%). We have had the case of a 75-year-old woman with metabolic acidosis as a result of metformin assumption, treated by renal replacement therapy (CRRT) with continuous veno-venous hemodiafiltration (CVVHDF).after a short treatment period there was a reduction in Lactates (from 16.8 mmol/L to 12.6 mmol/L) and a progressive improvement of acidosis. In 72 hours the recovery of diuresis and subsequent suspension of CRRT was achieved.CRRT, in addition to ensuring support for renal failure and volume correction, allowed a rapid recovery from metformin-associated lactic acidosis.

AIM: To perform an empirical, single-centre, retrospective and secondary cost of illness (COI) study of advanced ovarian carcinoma (AOC) in Italy. METHODS: Demographic, clinical, health care and non-health care resource consumption data concerning a convenience sample of subsequent patients in 1st line of treatment (100 patients), 2nd line of treatment A (surgery + chemotherapy; 30 patients) and 2nd line of treatment B (chemotherapy only; 20 patients) were obtained from a database created in 2011 by the Obstetrics and Ginecology Unit at Campus Biomedico teaching hospital, Rome. Patients were followed-up for 2 years. Resources were valued according to the above mentioned database and literature, following the societal viewpoint. Costs are expressed in Euro (€) 2014 and reported as mean and standard deviation (SD). RESULTS: One-year COI for 1st line of treatment reaches € 44,999.7 (SD: €28,757.3), € 55,410.8 (SD: € 32,454.6) and €46,895.6 (SD: € 28,407.4) for 2nd line of treatment A and B, respectively. Regardless the line of treatment, COI is mainly driven by cost borne by patient and her family. Due to the high costs of relapse the mean COI per patient after 2 years from the diagnosis of AOC equals € 81,869.4 (SD: € 30,660.9), or 182% of the COI for the 1st line of treatment. CONCLUSIONS: Despite some limitations, our results show that increasing progression-free survival could well reduce the COI for AOC in Italy.

INTRODUCTION:Payment by result agreements have been quite widely used in Italy to provide access for high costs oncologic drugs and minimize uncertainties of real life benefits (1). The aim of this analysis was to overview the Roche experience in terms of Payment by Result (Pbr) in oncology and investigate the relation between timing for the evaluation of treatment failures and observed Time to Off Treatment (TTOT) from Phase III clinical trials (2).METHODS:A retrospective analysis of the Roche payment by results schemes in place in Italy was conducted. For each drug included in the analysis it was collected: (i) the negotiated timing to assess the treatment failure for payment by result, (ii) the median time to off treatment curve observed in clinical trials for the experimental drug, (iii) the median time to off treatment observed in clinical trials for the control arm. The mean ratios between timing to assess the treatment failure for payment by result and the time to off treatment observed for the experimental drug or the median time to off treatment observed in the control arm were calculated to identify potential correlations. High level of correlation was expected if ratio was close to 1 (±.2).RESULTS:Roche products or different indications of the same product were identified as candidates for the analysis from 2008 to 2016. The timing for the evaluation of treatment failures for Pbr varies between 2 and 9 months, depending on the type of tumor and line of therapy. The mean Time to Payment By Result (TTPbr) / Control arm Time To Off Treatment (cTTOT) ratio was 1.16 (±.37) while the mean Time to Payment By Result (TTPbr) / Experimental arm Time To Off Treatment (eTTOT) ratio was .71 (±.13). Data analysis according to different time periods shows that the mean TTPbr/cTTOT and TTPbr/eTTOT for drugs negotiated from 2008 to 2015 were respectively 1.07 and 1.39 whereas for drugs negotiated in 2016 were respectively and .63 and 1.CONCLUSIONS:Good level of correlation between TTPbr and cTTOT was found. This finding is in line with the methodology used by Italian Medicines Agency so far, leveraging the cTTOT as the most appropriate proxy to assess any incremental effect of a new drug compared to the previous Standard of Care. The analysis over time of TTPbr shows that in the first years of payment by result negotiation TTPbr is more correlated to the cTTOT whereas in the last years is moving closer to the experimental one.

INTRODUCTION:In the past decades the cost-effectiveness of new effective disease-modifying therapies (DMTs) for Relapsing Remitting Multiple Sclerosis (RRMS) form was assessed through decision analytical models. Recently, new treatment option for the Primary Progressive (PPMS) form was developed. Aim of this work was assessing the similarities and differences of PPMS and RRMS and their impact in the development of decision analytical model for PPMS.METHODS:Literature review was performed to retrieve information on natural history of PPMS and RRMS and impact of DMTs agents on the progression of these conditions. Further, a review of the published cost-effectiveness models for RRMS was performed. Based on these data, an analysis on the difference and similarities between the two MS forms that could have an impact on the development of decision analytical model for PPMS was performed.RESULTS:Based on the analysis, similar structure model used for RRMS could be applied for PPMS. Health states of the model could be based on Expanded Disability Status Scale score as already done for RRMS. The relapse events considered for RRMS should not be included in PPMS model, and no possibility to develop another form, as the Secondary Progressive, should be included. While RRMS models should include at least a second line treatment option due to alternative DMTs available, only first treatment line should be considered for PPMS. Assessing data available to populate the model, poor data on the natural history, utility and cost associated to PPMS were available and assumption or expert opinions will be needed to overcome the lack of robust data.CONCLUSIONS:A decision analytical model for PPMS can use a similar structure used in the models for RRMS. However, more robust data on PPMS and some structural change are needed to provide a good tool to assess cost-effectiveness of DMTS in PPMS.

INTRODUCTION:In a budget constrained environment characterized by an increasing number of high-cost medicines, manufacturers need to demonstrate that their drugs can provide value-for-money. In this complex environment Managed Entry Agreements (MEAs) have been developed with the aim of sharing the risk between the National Health Service (NHS) and manufacturers (1). The objective of this analysis was to identify a correlation between Anatomical Therapeutic Chemical Classification (ATC) and different type of agreements assigned taking into consideration the distribution of Italian Medicines Agency registries by ATC and by kind of agreement negotiated (financial or performance based) (2).METHODS:This analysis takes into account all drugs under monitoring AIFA registries in place in Italy from 2006. For each registry included in the analysis it was collected the status of the registry (active, closed or incoming), the disease area that the registry covers and the monitored drugs with or without an associated Managed Entry Agreements. Considering the high weight of oncology drugs, a sub-analysis was done to investigate registries distribution for each specific form of cancer.RESULTS:The majority of drugs monitored are under a registry with no associated risk sharing agreement according to AIFA (60 percent). For what concerned monitored drugs with an associated agreement, performance-based agreement is the most diffused type of MEA. In terms of therapeutic area involved in the monitoring registries activity, oncology was the most common area. Financial based agreements characterize principally medicines used for Leukemia and Hepatitis C, whereas drugs administrated for Melanoma, Breast and Ovarian Cancer and Ophthalmology diseases follow performance based agreements.CONCLUSIONS:MEAs represent a way to guarantee a sustainable access for innovative medicines. It is proven that oncology products are most likely to have a MEA since they represent some of the most expensive drugs launched in recent years. From this study appear a correlation between the therapeutic disease area of the monitored drugs and MEA assigned by AIFA which is influenced also by other factors like budget impact, risk-benefit ratio and the presence of appropriate endpoints to evaluate the treatment response.

INTRODUCTION:The Italian Medicines Agency Registry represents a tool that could be a precious source of information regarding the mean treatment duration of a drug in a real world context. Monitoring registries are applied at the national level after market authorization and are designed not only to apply the Managed Entry Agreements (MEAs) but also to collect Real World Data on drugs safety, effectiveness and real life utilization. The purpose of this analysis was to compare the treatment duration from clinical trials and the mean treatment duration calculated using data from monitoring registries (1).METHODS:For each drug included in the analysis it was collected the treatment duration from Time To Off Treatment curves for the experimental drug (eTTOT) from Phase III clinical trials and the mean treatment duration data calculated by using the number of cycles (converted in months of treatment) of all treated patients extracted from AIFA registries (TTAR). The mean ratios between the Time of Treatment of Italian Medicines Agency and Experimental arm time to off treatment were calculated to identify potential correlations. High level of correlation was expected if Time to Payment By Result /Time To Off Treatment ratio was close to 1 (±.2).RESULTS:Six Roche products or different indications of the same product were identified as candidates for the analysis from 2013 to 2016. The mean TTAR/eTTOT ratio observed in patients treated from 2013 to 2016 was .97 (±.10), meaning that the mean treatment duration calculated from AIFA Registries is strongly comparable with the treatment duration observed in clinical trials. In one case the TTAR is even more major than eTTOT.CONCLUSIONS:A high level of correlation between TTAR and eTTOT was found. Additional analyses considering different cohorts of patients over time could be useful to have a more precise estimate of real world drug utilization. Even though RCTs remain the gold standard for demonstrating clinical efficacy in restricted trial setting, Real World Evidence from AIFA registries can contribute to the evidence base needed for healthcare decisions.