Nello Martini

Off-label use of medicines in children: can available evidence avoid useless paediatric trials?

PurposeIn some cases of drug therapy, the available evidence might be sufficient to extend the indications to children without further clinical studies.MethodsWe reviewed the available evidence for one of the categories of drugs most frequently used off-label in children: proton pump inhibitors (PPIs) used for the treatment of gastroesophageal reflux disease (GERD). A classification of the appropriateness of off-label use of PPIs in children with GERD was also performed.ResultsOf the five PPIs evaluated, only omeprazole has a paediatric indication in Europe. Overall, 19 clinical trials were retrieved and evaluated on the basis of pharmacokinetics, efficacy and safety data. The off-label use of omeprazole, esomeprazole and lansoprazole in children was evaluated as appropriate given the consistent available evidence retrieved in literature.ConclusionThis study demonstrates the existence of a large body of clinical evidence on the use of PPIs in children. Regulatory agencies and ethical committees should cope with this issue for ethical reasons to avoid unnecessary trial replication.

Current national initiatives about drug policies and cost control in Europe: the Italy example.

Abstract:Pharmaceutical expenditure is a challenge to the financial compatibility of health systems because it is growing faster (+11% per year in the last 5 years in Italy) than any other health sector. In order to curb public pharmaceutical expenditure 2 interventions are commonly used: delisting (de-reimbursement) and reference price, with the difference being paid by patients. The Italian Ministry of Health implemented a set of interventions with the general aim of pharmaceutical governance based on the following criteria: (a) to assure a complete coverage of all clinically and epidemiologically relevant diseases; (b) to provide health professionals with a range of different active drugs with the same therapeutic indications within the same therapeutic class; and (c) to identify a reimbursement threshold in order to save public money by narrowing the (wide) price differentials among drugs with comparable efficacy and safety. In this context, interventions have been undertaken at several levels including drug price reduction, generic drug promotion, delisting of drugs reimbursed, and direct distribution of medicines (by hospital services). Furthermore, a new National Pharmaceutical Formulary has been implemented. Medicines have been classified into homogeneous categories (ie, medicines with the same main indication(s) and with similar clinical efficacy and safety profile). Within each homogeneous category, a reimbursement level (cutoff) was then identified and, accordingly, pharmaceutical companies were asked to adjust their price. This adjustment was based on price per daily drug dose (DDD), cumulative expenditure (at least 50%), and cumulative utilization (at least 60%). This readjustment, at no cost for patients, is expected to save more than &U20AC;280 million of public money. Seventy-seven percent of this saving will be due to price readjustment of antiulcers, calcium channel blockers, angiotensin-converting enzyme (ACE) inhibitors, and some antibiotics (mainly cephalosporins). The Italian system was able to cover all relevant diseases and ensured citizens and health professionals a choice among a wide range of valid pharmacological therapies. At the same time it was able to save public money by narrowing wide price differentials among drugs with comparable clinical properties. The set of interventions yielded a new national formulary that was able to have a significant influence on the trend of drug expenditure in Italy. This experience can be a useful reference for other European and non-European states.

Natalizumab : a country-based surveillance program

Natalizumab is a humanized monoclonal antibody with a selective adhesion-molecule inhibitor effect, and a demonstrated efficacy in decreasing the frequency of relapses and progression of disability in relapsing-remitting multiple sclerosis (RR MS). After the approval of FDA and EMEA in MS cases unresponsive to immunomodulating therapy or in severe MS patients also not previously treated with interferons, and considering the concern on the possible side effects, an accurate program of surveillance was organized in our country by a combined effort of AIFA, Cineca, Department of Pharmacology of University of Bologna, and a group of neurologists appointed by the National Society of Neurology (SIN). After 15 months from the authorization of natalizumab therapy in MS, as of 31 March 2008, 908 cases have been treated with natalizumab and enrolled in this pharmaco-vigilance study. The mean age is 35 years, while the duration of disease is longer and disability is higher than that reported in the registrative study. Side effects are at the moment mild and similar to those previously described. At follow-up, the majority of treated cases are stable or ameliorated. The treatment was discontinued in 6% of patients.

Burden of disease, healthcare pathways and costs of cardiovascular high-risk patients with type 2 diabetes: a real world analysis

Objective: To estimate the burden of disease and to describe healthcare pathways and costs of type-2diabetes (DMT2) patients at high cardiovascular risk (HRCV). Methods: A real-world analysis was performed by using a subset of the AR-CO database, containing administrative health data of >4.3 million of inhabitants. A cohort of adult patients with DMT2 and HRCV was selected in 2013, and followed for 1 year. Through this period, information on antidiabetic and cardiovascular therapies, other co-treatments, hospitalisations, and outpatient services, was collected and analysed. The costs associated with each variable were assessed to estimate the integrated health care expenditure. Results: Overall, 7,167 patients with DMT2 and HRCV were identified, corresponding to 3.1% of all diabetic patients and 0.2% of adult population. During the 1-year follow-up, 90.1% of the cohort received at least a prescription of an antidiabetic drug, 98.0% of a cardiovascular medication and 95.9% used at least an outpatient service. 44.5% had an admission during the follow-up period, especially for cardiovascular events. The integrated cost analysis showed that the overall average cost for each subject was € 13,567. Hospitalisations generated 86.8% of this expenditure, followed by drugs (7.7%) and by outpatient services (5.5%). Conclusions: Although patients with DMT2 and HRCV represent a small percentage of the overall population with diabetes, they generate very high costs for National Healthcare System. These costs are mainly due to the hospitalisations, especially for cardiovascular events. New therapeutic strategies involving these patients should allow reduction of hospital admission, resulting in savings for National Healthcare System.