The FDA qualitative assessment can be guided by a framework,27 in a way similar to that of the EMA. This framework supports and formalizes the BRA judgment. It allows in particular standardization of the consistency and transparency in the BRA process and decision, which is essential for the prescribes, the patients, and the pharmaceutical industry. In Europe, the EMA published in 2008 a paper entitled Reflection Paper on Benefit-Risk Assessment Methods in the context of the Evaluation of Marketing Authorisation Applications of Medicinal Inhibitors,research,lifescience,medical Products for Human Use: 28 The Agency explored approaches to improving the methodology for this assessment and the

consistency and transparency of the evaluations. For the EMA, as for the FDA, assessments by experts are essential in BRA, and quantitative approaches do not yet replace this qualitative assessment. Two main Inhibitors,research,lifescience,medical conclusions emerge from the EMA paper. First, the Agency proposes the use of a specific template for the benefit-risk section of the drug dossier, with specific guidance for the assessors. Hiis guidance allows summarization ol the Inhibitors,research,lifescience,medical main data about benefits and risks of the evaluated drug

in a structured manner. In particular, the BRA must be performed considering the therapeutic context of the assessed drug. The reflection paper also emphasizes the uncertainties and variability of these estimations and their impact on the decision. Second, it contains an acknowledgment of the need to support research in the development of quantitative or semiquantitative BRA methodologies. The recently created European Network of Centres for Pharmacoepidemiology and Pharmacovigilance is part of this initiative. Inhibitors,research,lifescience,medical Clearly, the FDA and the EMA still rely on expert opinions and qualitative assessment, and not yet on quantitative methods, to summarize the evidence obtained in clinical trials to construct the BRA prior to registration of new drugs. But both agencies encourage the use of frameworks to structure

these assessments in order Inhibitors,research,lifescience,medical to ensure consistency in the evaluation and decisions. Discussion Contrary to the drug efficacy, for which statistical tests can be used to demonstrate superiority of an experimental drug over a comparator in a controlled study design, the methodology to demonstrate in a definitive way the safety ol a treatment is less straightforward and cannot be fully captured enough by randomized controlled studydesign. For a given safety issue, the risk can be estimated on the basis of incidences of ADR compared between active and reference treatments; however, the safety profile of a drug includes numerous safety issues, and it is difficult to summarize this learn more configuration into a onedimensional concept. Moreover, once the safety risks are identified, in a benefit-risk perspective, one needs to define the acceptance level for each of the risks.