Price and reimbursement of advanced therapeutic medicinal products in Europe: are assessment and appraisal diverging from expert recommendations?

BACKGROUND: Advanced therapy medicinal products (ATMPs) represent an important cornerstone for innovation in healthcare. However, uncertainty on the value, the high average cost per patient and their one-shot nature has raised a debate on their assessment and appraisal process for pricing and reimbursement (P&R) purposes. This debate led experts providing for recommendations on this topic. Our primary objective is to investigate the ATMPs P&R process in the main five European countries and to understand if this process is consistent with published P&R expert recommendations. We also investigated the current ATMP pipelines to understand if future ATMPs will create challenges for their P&R process. METHODS: P&R framework for ATMPs in the European Major five (EU5) countries was investigated through a literature search on PubMed, institutional websites of National Health Authorities and grey literature. The ATMPs pipeline database was populated from a clinical trial database (clinicaltrials.gov), relying on inclusion and exclusion criteria retrieved from the literature. RESULTS: Reimbursement status of ATMPs is different across the EU5 countries, with the exception of CAR-Ts which are reimbursed in all countries. Standard P&R process in place for other medicinal products is extended to ATMPs, with the exception of some cases in Germany. List prices, where available, are high and, tend to be aligned across countries. Outcome-based Managed Entry Agreements (MEAs) have been extensively used for ATMPs. Extra-funds for hospitals managing ATMPs were provided only in Germany and, as additional fund per episode, in France. The accreditation process of hospitals for ATMPs management was in most countries managed by the national authorities. As far as ATMPs pipeline is concerned, ATMPs in development are mostly targeting non-rare diseases. CONCLUSIONS: Expert recommendations for ATMPs P&R were partially applied: the role of outcome-based MEAs has increased and the selection process of the centres authorized to use these treatments has been enhanced; additional funding for ATMPs management to accredited centres has not been completely considered and annuity payment and broader perspective in cost considerations are far from being put in place. These recommendations should be considered for future P&R negotiations to pursue rational resource allocation and deal with budget constraints.

Percutaneous cryoablation vs. open partial nephrectomy in small kidney cancers: the Italian experience.

INTRODUCTION: The aim of the present work was to analyze the economic impact of PCA (percutaneous cryoablation) vs. OPN (open partial nephrectomy), as it represents the most common standard of care for SRMs (small renal masses), namely T1a renal cancers (<4 cm), in Italy. EVIDENCE ACQUISITION: A cost analysis was performed to compare the difference of the total perioperative costs between PCA and OPN, both from the perspective of the National Healthcare System and the hospital. Clinical and resources consumption inputs were retrieved by a non-systematic literature search on scientific databases, complemented by a grey literature research, and validated by expert opinion. Costs calculation for the NHS perspective were based on reference tariffs published by the National Ministry of Health, while for the hospital perspective, unit costs published in the grey literature were used to compare the two alternatives. EVIDENCE SYNTHESIS: Assuming the NHS perspective, the cost analysis shows there is an economic advantage in using PCA vs. OPN (€4080 vs. €7541) for the treatment of SRMs. Hospitalization time is the driver of the total costs, while the costs of complications are quite negligible in both groups. From the hospital perspective the costs of PCA is slightly higher (+€737) than OPN, with cryoprobes contributing as the greatest cost component. However, this increase is quite restrained and is offset by an inferior use of healthcare resources (surgery room, healthcare personnel, length of stay in the hospital). CONCLUSIONS: According to our analysis, PCA results an advantageous technique compared to OPN respectively in terms of costs and resource consumption from both the NHS and the hospital perspective.

The burden of atopic dermatitis in adults in Italy.

BACKGROUND: Moderate-to-severe atopic dermatitis (AD) generates a considerable consumption of healthcare resources and significant economic consequences for the patients and their families, healthcare systems (NHS) and society. Several studies on the burden of AD in paediatric patients are available in literature, while data in adults is scant. The purpose of this study was to estimate the direct and indirect costs of moderate to severe AD in adult patients in Italy. METHODS: Patients with Eczema Area and Severity Index (EASI) Score >20 were included in a multicentre, observational study conducted in six outpatient dermatology clinics throughout the national territory. Data were retrospectively gathered through a case report form investigating healthcare resources consumption, out-of-pocket expenses and patients' and caregivers' productivity loss. Descriptive statistics was used to illustrate data. Univariate generalized linear model with gamma distribution and identity function link was used to describe association between costs and disease severity. RESULTS: A total of 50 patients with a diagnosis of moderate-to-severe DA (EASI Score ≥20), equal to 89% of the total, were included in the analysis. The total annual burden of the disease, direct and indirect costs, amounted to € 4284 per patient; 19.3% accounted for direct medical costs, 19.9% for direct non-medical and 60.8% for indirect costs due to productivity loss. CONCLUSIONS: Moderate-to-severe AD in adults represents an important cost for the society imposing a high financial burden for the NHS, but even more for patients and caregivers. Results from this study may support identification of potential factors impacting on the choice of new therapeutic options to improve the clinical and economic management of this devastating disease.

Persistence on apixaban in atrial fibrillation patients: a retrospective multicentre study.

AIMS: Real-world data on treatment persistence, safety and effectiveness of non-Vitamin K antagonist oral anticoagulants (NOACs) play an important role in the assessment of risks and benefits of these drugs. Our aim was to evaluate persistence on treatment, incidence of major bleeding and incidence of a composite endpoint of major events, including all-cause death, myocardial infarction, stroke and systemic thromboembolism, during treatment with apixaban in a cohort of patients with nonvalvular atrial fibrillation (NVAF). METHODS: In this multicentre retrospective observational study, we retrieved data from medical records of five Italian hospitals on patients with a diagnosis of NVAF who initiated apixaban between 1 January 2014 and 31 March 2016 and had a first subsequent visit at the same hospital. RESULTS: We studied 766 patients with mean age of 74.2 (standard deviation 11.1) years and median CHADS2 and CHA2DS2VASc scores of 2.0 and 4.0, respectively. Over a median follow-up period of 339 days, persistence on treatment was 83.5% [95% confidence interval (95% CI) 75.5-89.1%]. The rate of major bleeding (per 100 person-years) was 1.15 (95% CI 0.39-1.90 per 100 person-years), while the cumulative incidence was 4.4% (95% CI 1.6-12.0). The rate of major events was 1.97 (95% CI 1.08-2.86) per 100 patient-years, with a cumulative incidence over the entire follow-up period of 7.7% (95% CI 4.6-12.8). CONCLUSION: In real-life conditions, NVAF patients treated with apixaban show rates of treatment discontinuation and major bleedings, which are comparable to those found in the ARISTOTLE pivotal study, thus supporting its external validity.

Primary Biliary Cholangitis: advances in management and treatment of the disease.

Primary Biliary Cholangitis, previously known as Primary Biliary Cirrhosis, is a rare disease, which mainly affects women in their fifth to seventh decades of life. It is a chronic autoimmune disease characterized by a progressive damage of interlobular bile ducts leading to ductopenia, chronic cholestasis and bile acids retention. Even if the disease usually presents a long asymptomatic phase and a slow progression, in many patients it may progress faster toward cirrhosis and its complications. The 10year mortality is greater than in diseases such as human immunodeficiency virus/Hepatitis C Virus coinfection and breast cancer. Ursodeoxycholic acid is the only treatment available today, but even if effective in counteracting the disease progression for the majority of patients, in approximately 40% is not able to decrease effectively the alkaline phosphatase, a surrogate marker of disease activity. Recently, obeticholic acid received the European Medicines Agency conditional approval, as add on treatment in patients non responders or intolerant to ursodeoxycholic acid. The present paper illustrates the opinion of a working group, composed by clinical pharmacologists, gastroenterologists/hepatologists with specific expertise on Primary Biliary Cholangitis and patient associations, on the state of the art and future perspectives of the disease management. The agreement on the document was reached through an Expert Meeting.