Comparison of the pharmacokinetics (PK) of a coagulation factor between groups of patients can be biased by differences in study protocols, in particular between blood sampling schedules. This could affect clinical dose tailoring, especially in children. The aim of this study was to describe the relationships of the PK of factor VIII (FVIII) with age and body weight by a population PK model. The potential to reduce blood sampling was also explored. A model was built for FVIII PK from 236 infusions of recombinant FVIII in 152 patients (1-65 years of age) with severe hemophilia A. The PK of FVIII over the entire age range was well described by a 2-compartment model and a previously reported problem, resulting from differences in blood sampling, to compare findings from children and adults was practically abolished. The decline in FVIII clearance and increase in half-life with age could be described as continuous functions. Retrospective reduction of blood sampling from 11 to 5 samples made no important difference to the estimates of PK parameters. The obtained findings can be used as a basis for PKbased dose tailoring of FVIII in clinical practice, in all age groups, with minimal blood sampling. (Blood. 2012;119(2): 612-618)

Access to and sharing of data are essential for the conduct and advancement of science. This article argues that publicly funded research data should be openly available to the maximum extent possible. To seize upon advancements of cyberinfrastructure and the explosion of data in a range of scientific disciplines, this access to and sharing of publicly funded data must be advanced within an international framework, beyond technological solutions. The authors, members of an OECD Follow-up Group, present their research findings, based closely ontheir report to OECD, on key issues in data access, as well as operating principles and management aspects necessary to successful data access regimes.

To cite this article: Collins PW, Bjö rkman S, Fischer K, Blanchette V, Oh M, Schroth P, Fritsch S, Casey K, Spotts G, Ewenstein BM. Factor VIII requirement to maintain a target plasma level in the prophylactic treatment of severe hemophilia A: influences of variance in pharmacokinetics and treatment regimens. J Thromb Haemost 2010; 8: 269-75.Summary. Background: Prophylactic factor (F)VIII has been shown to reduce bleeds and arthropathy in patients with severe hemophilia A. Objectives: Assuming that the trough FVIII level is an important determinant of the efficacy of prophylaxis, this paper addresses the effect of the inter-patient variability in pharmacokinetics and different dosing regimens on trough levels. Methods: Simulations used FVIII half-lives and in vivo recoveries (IVR), observed during clinical trials with Advate [Antihemophilic Factor (Recombinant), Plasma/Albumin-Free Method], and commonly used prophylactic regimens to calculate their effect on FVIII levels during prophylaxis. Results and conclusions: Half-life and dose frequency had a larger effect on trough FVIII and time per week with FVIII < 1 IU dL )1 than IVR and infused dose per kg. The combined effect of these parameters resulted in substantial inter-patient variability in the amount of FVIII required to sustain a desired trough level. Prophylactic regimens based on Monday, Wednesday, Friday dosing were less cost effective in maintaining a desired trough level throughout the week. Dose escalation on Friday to cover the weekend would require potentially harmful doses of FVIII in many patients, especially in young children where more than 50% would require a Friday dose of over 100 IU kg )1 and some would require more than 400 IU kg )1. Knowledge of individual patientsÕ half-lives and alteration of frequency of infusions may allow the more cost-effective use of FVIII and potentially expand access to prophylaxis to a greater number of patients, especially in regions where healthcare resources are scarce.

POMR should be reported as a health indicator by all countries and regions of the world. POMR reporting is feasible, credible, achieves a consensus of acceptance for reporting at national level. Hospital and Service level POMR requires interpretation using simple measures of risk adjustment such as urgency, age, the condition being treated or the procedure being performed and ASA status.

No abstract