g. Bayesian [2] and Adaptive Design [3]) and statistical modelling for the design of prelicensure trials for new unmodified and novel factor VIII (FVIII), factor IX (FIX) and FVIII/FIX bypassing therapeutics

in previously treated patients (PTPs). Previously untreated patient (PUP) studies will subsequently be considered, as these are currently required by the EMA for novel product registration. With the goal of study optimization, the PG is examining the impact of these alternative strategies on the type and number of subjects, as well as the CFC exposure days required to achieve the current safety and efficacy endpoints for product authorization. As part of this exercise, the group will also evaluate the statistical targets for the prelicensure determination

of product safety (defined by neoantigenicity) for both novel and unmodified FVIII and FIX CFCs. In addition, the Pirfenidone in vitro PG is considering the feasibility selleck of using postlicensure studies to validate current immunological definitions of neoantigenicity and to study emerging immunological biomarkers of treatment-related antibody development for future incorporation into exploratory clinical trial design models. The PG is examining the current tenets of clinical efficacy determination in a similar way. In collaboration with the Definitions Project Group of the FVIII/IX Subcommittee, this PG is pursuing the potential implementation of more precise definitions for subject inclusion criteria and clinical outcome endpoints (e.g. clinical severity; non-transient inhibitor; inhibitor eradication; exposures; prophylaxis; haemorrhage; and response to therapy) as a way to maximize data generation on clinical efficacy in preregistration studies. Furthermore, the group will consider the possible role of surrogate markers (e.g. pharmacokinetics) in ascertaining clinical efficacy in preregistration trials when complimented by mandatory rigorous data collection on clinical effectiveness through prospectively designed postlicensure studies. As its work is ongoing, the Clinical Trial Design for Hemophilia Project Group has not

yet formalized any recommendations. However, its deliberations to date will be shared during the presentation of this paper. In conclusion, advances in potential therapeutics for the haemophilias have necessitated MCE公司 a re-examination of the current approach to new product trials and studies. It has also provided unprecedented opportunity for the bleeding disorders community to collaborate in the investigation of new paradigms for future clinical studies and, in so doing, to generate international harmonized databases to guide new product regulation and systematic implementation into evidence-based clinical care. None. In 2001, White et al. reported consensus definitions in haemophilia on behalf of the Factor VIII and IX Subcommittee of the SSC of the ISTH [4].