The latter hypothesis requires more investigation, which is also the case for GDC-0068 research buy understanding the optimal dosing required to allow this potential benefit of prophylaxis to occur. For most

of the other debated non-genetic factors, the impact on the immunological outcome is, to date, not supported by the literature. Because the factors are often interrelated, it is also difficult to identify the relative contribution of each. This is also reflected by the results of the survey carried out among the EHTSB members, in which the impact of the majority of the factors was extremely variable; a pattern also recently reported in a survey by van den Berg and Chalmers [68]. The genetic profile of the patient will have a major impact on the immunological outcome and must be considered. This has not been done in the current literature. As haemophilia is a rare disease, and inhibitors develop in a minority of patients,

selleck chemical the statistical power of studies addressing these issues will, by definition, be limited. In light of the complexity of the aetiology of inhibitor development, future research should be directed at the identification of early immunological markers of high risk patients. In 2007, the EMEA [8] produced a report that defined many of the variables that should be considered when evaluating the literature on inhibitor formation. Unfortunately, several of these variables have not been included in a substantial 上海皓元医药股份有限公司 number of published studies, which will indeed influence the accuracy, validity and interpretation of the data. For example, the type of assay used to measure and to identify the inhibitor. The Nijmegen modification of the Bethesda assay was considered the ‘gold standard’ with a cut-off point of >0.6 BU. In addition, confirmatory tests on a second, separately drawn sample within a month should be performed. As seen in the tables, however,

these requirements are frequently not adhered to by studies published in the current literature. Moreover, the previous exposure to factor concentrates will be of major importance. According to the EMEA report, PUPs should be defined as those patients who have never been exposed to clotting factor products. Frequently, inhibitor studies involve patients who are considered to be MTPs. This term was considered inappropriate and these patients should instead be defined as previously treated patients (PTPs). This will have an impact on the interpretation of inhibitor incidence in each cohort described. It was also suggested that the number of EDs should be utilized as parameters to categorize risk rather than rely on the categories of PUP or MTP. In the case of factor concentrate immunogenicity, it was agreed that PTPs was the optimal group to study to limit the impact of confounding factors.