Variation in the prices of oncology medicines across Europe and the implications for the future

Introduction/ Objectives: There are increasing concerns among health authorities regarding the sustainability of healthcare systems with growing expenditure on medicines including new high-priced oncology medicines. Medicine prices among European countries may be adversely affected by their population size and economic power to negotiate. There are also concerns that prices of patented medicines do not change once the prices of medicines used for negotiations substantially change. This needs to be investigated as part of the implications of low-cost generic oncology medicines. Methodology: Analysing principally reimbursed prices of patented oral oncology medicines (imatinib, erlotinib and fludarabine) between 2013 and 2017 across Europe and exploring correlations between GDP, population size, and prices. Comparing the findings with previous research regarding prices of oral generic oncology medicines. Results: The prices of imatinib, erlotinib and fludarabine did vary among European countries but showed limited price erosion over time in the absence of generics. There appeared to be no correlation between population size and prices. However, higher prices were seen among countries with higher GDP per capita which is a concern for lower income countries referencing these. Discussion and Conclusion: It is likely that the limited price erosion for patented oncology medicines will change across Europe with increased scrutiny over their prices and value as more medicines used for pricing decisions lose their patents combined with growing pressures on the oncology drug budget. In addition, discussions will continue regarding fair pricing for new oncology medicines and other approaches given ever rising prices with research showing substantial price reductions for oral oncology medicines (up to -97.8% for imatinib) once generics become available. We are also seeing appreciable price reductions for biosimilars further increasing the likelihood of these developments

Tensile Test and Interface Retention Forces Between Wires and Composites in Lingual Fixed Retainers

Introduction: In daily orthodontic clinical practice retention is very important, and lingual retainers are part of this challenge. The failure of lingual retainers may be due to many factors. The aim of this study was to assess the retention forces and mechanical behavior of different types of wires matched with different kinds of composites in lingual retainers. Methods: A tensile test was performed on cylindrical composite test specimens bonded to orthodontic wires. The specimens were constructed using four different wires: a straight wire (Remanium .016 7.022\u2033 Dentaurum), two round twisted wires (Penta One .0215\u2033 Masel, Gold Penta Twisted .0215\u2033 Gold N'braces) and a rectangular braided wire (D-Rect .016 7.022\u2033 Ormco); and three composites: two micro-hybrids (Micro-Hybrid Enamel Plus HFO Micerium, and Micro-Hybrid SDR U Dentsply) and a micro-nano-filled composite (Micro-Nano-Filled Transbond LR 3M). The test was performed at a speed of 10mm/min on an Instr\uf6m device. The wire was fixed with a clamp. Results: The results showed that the bonding between wires and composites in lingual fixed retainers seemed to be lowest for rectangular smooth wires and increased in round twisted and rectangular twisted wires where the bonding was so strong that the maximum tension/bond strength was greater than the ultimate tensile strength of the wire. The highest values were in rectangular twisted wires. Concerning the composites, hybrid composites had the lowest interface bonding values and broke very quickly, while the nano- and micro-composites tolerated stronger forces and displayed higher bonding values. The best results were observed with the golden twisted wire and reached 21.46 MPa with the Transbond composite. With the rectangular braided wire the retention forces were so high that the Enamel Plus composite fractured when the load exceeded 154.6 N/MPa. When the same wire was combined with the Transbond LR either the wire or the composite broke when the force exceeded 240 N. Conclusions: The results of this study show that, when selecting a lingual retainer in daily clinical practice, not only must the patient's compliance and dependability be considered but also the mechanical properties and composition of different combinations of composites and wires

Time to Review Authorisation and Funding for New Cancer Medicines in Europe? Inferences from the Case of Olaratumab

The potential benefits of early patient access to new medicines in areas of high unmet medical need are recognised, but uncertainties concerning effectiveness, safety and added value when new medicines are authorised, and subsequently funded based on initial preliminary data only, have important implications. In 2016 olaratumab received accelerated conditional approval from both the European Medicines Agency and the US Food and Drug Administration for the treatment of soft-tissue sarcoma, based on the claims of a substantial reduction in the risk of death with an 11.8-month improvement in median overall survival in a phase II trial in combination with doxorubicin vs. doxorubicin alone. The failure to confirm these benefits in the post-authorisation pivotal trial has highlighted key concerns regarding early access and conditional approvals for new medicines. Concerns include potentially considerable clinical and economic costs, so that patients may have received suboptimal treatment and any money spent has foregone the opportunity to improve access to effective treatments. As a result, it seems reasonable to reconsider current marketing authorisation models and approaches. Potential pathways forward include closer collaboration between regulators, pharmaceutical companies and payers to enhance the generation of rapid and comparative confirmatory trials in a safe and fair manner, with minimal patient exposure as required to achieve robust evidence. Additionally, it may be time to review early access systems, and to explore new avenues regarding who should pay or part pay for new treatments whilst information is being collected as part of any obligations for conditional marketing authorisation. Greater co-operation between countries regarding the collection of data in routine clinical care, and further research on post-marketing data analysis and interpretation, may also contribute to improved appraisal and continued access to new innovative cancer treatments

A predictive clinical-genetic model of tissue plasminogen activator response in acute ischemic stroke

Wide interindividual variability exists in response to tissue plasminogen activator (t-PA) treatment in the acute phase of ischemic stroke. We aimed to find genetic variations associated with hemorrhagic transformation (HT) and mortality rates after t-PA. We then generated a clinical-genetic model for predicting t-PA response