Estimation of Direct Melanoma-related Costs by Disease Stage and by Phase of Diagnosis and Treatment According to Clinical Guidelines.

Cutaneous melanoma is a major concern in terms of healthcare systems and economics. The aim of this study was to estimate the direct costs of melanoma by disease stage, phase of diagnosis, and treatment according to the pre-set clinical guidelines drafted by the AIOM (Italian Medical Oncological Association). Based on the AIOM guidelines for malignant cutaneous melanoma, a highly detailed decision-making model was developed describing the patient's pathway from diagnosis through the subsequent phases of disease staging, surgical and medical treatment, and follow-up. The model associates each phase potentially involving medical procedures with a likelihood measure and a cost, thus enabling an estimation of the expected costs by disease stage and clinical phase of melanoma diagnosis and treatment according to the clinical guidelines. The mean per-patient cost of the whole melanoma pathway (including one year of follow-up) ranged from €149 for stage 0 disease to €66,950 for stage IV disease. The costs relating to each phase of the disease's diagnosis and treatment depended on disease stage. It is essential to calculate the direct costs of managing malignant cutaneous melanoma according to clinical guidelines in order to estimate the economic burden of this disease and to enable policy-makers to allocate appropriate resources.

CASE STUDY ON AN IPILIMUMAB COST-CONTAINMENT STRATEGY IN AN ITALIAN HOSPITAL.

OBJECTIVES: Ipilimumab is the first licensed immune checkpoint inhibitor for treatment of melanoma. The promising results of the registration clinical study need confirmation in real practice and its clinical success comes together with a relevant budget impact due to the high price of this drug. The aim of this work is to describe a new model of economical sustainability of ipilimumab developed in an Italian reference center for melanoma treatment. METHODS: This retrospective, observational, and monocentric study was carried out at the Veneto Institute of Oncology. Ipilimumab was administered to fifty-seven patients with advanced melanoma. Overall survival, progression free survival, and toxicity were evaluated. A local management procedure was evaluated together with the cost-saving strategies implemented by the Italian Medicines Agency (AIFA). RESULTS: We demonstrated that the use of ipilimumab for metastatic melanoma in real practice had an efficacy and toxicity similar to that reported in the literature. In this scenario, our management model (centralization of compounding + drug-day) permitted savings up to the 11.1 percent of the gross cost for the drug (calculated assuming that no cost saving procedures were applied) while the policy of cost containment designed by AIFA produced an additional 6.2 percent of savings. CONCLUSIONS: In real practice conditions, the centralized administration of ipilimumab allows to replicate the results of clinical studies and in the meantime to contain the cost associated with this drug. The local strategy of management can be readily applied to most of the high cost drugs compounded in the hospital pharmacy. Impact of findings on practice: (i) We describe a new model of economic sustainability (drug-day, centralization of compounding, payback systems) of an expensive and innovative drug, ipilimumab, for treatment of melanoma within an Italian cancer center. (ii) This pivotal study demonstrated that a cost containment strategy is feasible and it needs the cooperation of all healthcare providers (oncologists, pharmacists, nurses, and technicians) to guarantee the full efficiency of the process.

Hospital Pharmacy Response to Covid-19 Pandemic in Italy: What We Learned From the First Outbreak Wave.

BACKGROUND: When COVID-19 pandemic started, Italian hospital pharmacists faced multiple challenges and change their work practices. OBJECTIVES: The aim of this study was to describe the impact of COVID-19 emergency on pharmaceutical care provided by pharmacists during the first wave of the pandemic. Issues related to pharmacist's involvement in the pandemic management were: changes in activities, support received by authorities and pharmacists' own perceived role in the Health System. METHODS: A cross-sectional study based on a web survey was conducted between May and June 2020 collecting information from pharmacists, members of Italian Society of Clinical Pharmacy and Therapeutics. 113 (11.4%) completed the questionnaire. The cohort was divided in 2 arms: pharmacists who worked in severely COVID-19 affected areas (High Spread Regions) and those employed in less affected areas (Low Spread Regions). RESULTS: The changes in pharmacy work settings reflected the increase of logistics area and non-sterile clinical galenic, and reduction of clinical tasks. The most demanding challenge was referred to shortages of medical devices and drugs, 61/113 pharmacists reported difficulty in obtaining products compliant to quality standards. National Institutions and Regional Governments provided a greater perceived support. More than 50% of participants felt that their role did not change if compared to other health professionals. CONCLUSIONS: Despite some limitations related to their clinical activity, pharmacists played a crucial role in supplying personal protective equipment, medical devices and medications to improve health outcomes during this emergency. The results may guide pharmacists in future actions to improve the management of the pandemic.

Estimation of direct costs of melanoma in the Veneto Region: a budget assessment and cost-consequence analysis.

BACKGROUND: While many evidence-based pathways have been introduced to drive quality improvements in cancer care, most of these do not include evidence about their affordability. The main aim of this study was to provide an estimation of the overall budget to cover all the needs of melanoma patients in Veneto Region, managed according to the clinical pathway defined by the Rete Oncologica Veneta. A second objective is to conduct a cost-consequence analysis, comparing two different treatments. METHODS: A very detailed whole-disease model was developed describing the patient's pathway from diagnosis through the first year of follow-up. Each procedure involved in the model was associated with a likelihood measure and a cost. The model can be used to estimate the expected direct costs associated with melanoma. RESULTS: We can observe that 0 and I stage, despite accounting for a huge percentage of new melanoma cases are characterized by a small percentage of the total costs. Stage III can be considered as the most expensive stage accounting for 54% of the total costs with a 12% of patients. Finally, the stage IV patients, although very few accounts for almost the 7% of the total costs. Regarding the cost-consequence analysis, it was estimated that the therapies introduced in 2016 led to an approximately 14% increase in the total costs. CONCLUSIONS: Modeling a clinical pathway with a high level of detail enables to identify the main sources of spending. The consequent analysis can thus help policymakers to plan the future resources allocation.

Cost-effectiveness of a melanoma screening programme using whole disease modelling.

OBJECTIVE: To assess the potential impact of a melanoma screening programme, compared with usual care, on direct costs and life expectancy in the era of targeted drugs and cancer immunotherapy. METHODS: Using a Whole Disease Model approach, a Markov simulation model with a time horizon of 25 years was devised to analyse the cost-effectiveness of a one-time, general practitioner-based melanoma screening strategy in the population aged over 20, compared with no screening. The study considered the most up-to-date drug therapy and was conducted from the perspective of the Veneto regional healthcare system within the Italian National Health Service. Only direct costs were considered. Sensitivity analyses, both one-way and probabilistic, were performed to identify the parameters with the greatest impact on cost-effectiveness, and to assess the robustness of our model. RESULTS: Over a 25-year time horizon, the screening intervention dominated usual care. The probabilistic sensitivity analyses confirmed the robustness of these findings. The key drivers of the model were the proportion of melanomas detected by the screening procedure and the adherence of the target population to the screening programme. CONCLUSIONS: The screening programme proved to be a dominant option compared with usual care. These findings should prompt serious consideration of the design and implementation of a regional or national melanoma screening strategy within a National Health Service.

Bioethics: a challenge and an opportunity for hospital pharmacists.

OBJECTIVES: Traditionally, pharmacy ethics in Europe has held an insignificant place in the scheme of pharmaceutical education. We embraced the idea that bioethics should be an integral part of a pharmacist's education and professional practice, especially in hospital pharmacy where the concept of 'pharmaceutical care' should be revitalised to strengthen the broad-based and patient-oriented responsibilities of the clinical pharmacist. METHODS: We decided to structure a bioethics course tailored to pharmacists who are specialising in hospital pharmacy. We first created a training network partnership between a university and a research hospital to integrate classroom teaching with skill-specific practical experience. Our course pilot project introduces, in two of the four years of the national specialty programme, general topics and practical bioethical issues. RESULTS: A pilot course on ethics for the School of Specialisation in Hospital Pharmacy began at the Padua University in 2014. in February 2017 we contacted the same students again, asking them further questions about their experience. Several students asked to examine more cases and to deal with the few arguments that questioned them on an ethical level. On the whole, through the comments of trainees, the needs of those who are facing an unfamiliar subject, which is perceived as important, emerge. CONCLUSION: Even if we are aware that this is a pilot project and requires more data, dissemination of this experience into a wider network will help us to define an effective educational pathway in collaboration with other Specialty Schools of Hospital Pharmacy.

Safety and Tolerability of Anti-Angiogenic Protein Kinase Inhibitors and Vascular-Disrupting Agents in Cancer: Focus on Gastrointestinal Malignancies.

Angiogenesis is an essential process for tumor growth and metastasis. Inhibition of angiogenesis as an anticancer strategy has shown significant results in a plethora of tumors. Anti-angiogenic agents are currently part of many standard-of-care options for several metastatic gastrointestinal cancers. Bevacizumab, aflibercept, ramucirumab, and regorafenib have significantly improved both progression-free and overall survival in different lines of treatment in metastatic colorectal cancer. Second-line ramucirumab and third-line apatinib are effective anti-angiogenic treatments for patients with metastatic gastric cancer. Unfortunately, the anti-angiogenic strategy has major practical limitations: resistance inevitably develops through redundancy of signaling pathways and selection for subclonal populations adapted for hypoxic conditions. Anti-angiogenic agents may be more effective in combination therapies, with not only cytotoxics but also other emerging compounds in the anti-angiogenic class or in the separate class of the so-called vascular-disrupting agents. This review aims to provide an overview of the approved and "under development" anti-angiogenic compounds as well as the vascular-disrupting agents in the treatment of gastrointestinal cancers, focusing on the actual body of knowledge available on therapy challenges, pharmacodynamic and pharmacokinetic mechanisms, safety profiles, promising predictive biomarkers, and future perspectives.

Ipilimumab in real-world clinical practice: efficacy and safety data from a multicenter observational study.

In patients with metastatic melanoma, ipilimumab has been shown to improve long-term survival. This observational multicenter study reports clinical outcomes of 418 patients treated with second-line ipilimumab from February 2013 to August 2014. Median overall survival (OS) was 6.43 months (95%CI: 5.45-7.42; n = 300), while median progression-free survival (PFS) was 3.7 months (95%CI: 3.23-4.17; n = 188). Demographic factors, such as sex or number of previous therapies did not affect OS. Survival was shorter in patients with ECOG > 0 (Eastern Cooperative Oncology Group, Performance Status) (p < 0.001), while a longer OS was found in patients who completed all four therapy cycles (p < 0.001). Adverse events of any grade were reported for 66% of patients (mainly cutaneous and gastrointestinal), but most were low grade and easily managed. Adverse events of grades 3-4 were observed in 13% of patients. This study confirmed the efficacy and safety of this treatment in real practice.

A survey on patients medication reconciliation process in an oncological hospital.

OBJECTIVES: The purpose of this study was to assess the impact of medication reconciliation in the clinical practice from a hospital pharmacist point of view. METHODS: A survey of the medication taken by cancer patients was performed on admission and on discharge in an oncological hospital, and then the subjects were followed up until discharge for 8 weeks. The pharmacist entered the data collected into a computer based tool which, by using Screening Tool of Older Persons' Potentially Inappropriate Prescriptions (STOPP criteria) and Micromedex™ interactions database, automatically produces a report indicating the possible inconsistencies. The report is to check all potentially inappropriate prescriptions (PIPs) correlated to the drugs assumption by the patient. The appropriateness of the medication was scored using a Medication Appropriateness Index (MAI index) which was used to reconcile the medication list accordingly. RESULTS: Patients reconciled at admission were 98, while patients reconciled at discharge were 90, 8 patients dropped out due to death. After the intervention of the hospital pharmacist, the average value of MAI index showed a significant reduction (3,391 to 2,552 p=0.039) and the median number of drugs prescribed per patient was decreased (7 vs 6; p=0.8058). CONCLUSION: Our study demonstrated that the forms used in the reconciliation process, in particular the record card, is a promising method to increase the quality of the information related to drug use in clinical decisions. We think that medication reconciliation softwares should be widely used by health care professionals involved in the recording of drug history or prescription process.