After completing the first phase of a project designed to increase the consistency and transparency of the European Union regulatory process, the European Medicines Agency (EMA) published a summary report that includes suggestions for improving the current processes for evaluating benefit–risk.
The report was published following visits by the project team to the participating National Competent Authorities (France, The Netherlands, Spain, Sweden and the United Kingdom). Germany's Paul-Ehrlich-Institut, which volunteered to participate later in the project, was included in visits in February 2010.
"At present, there are no common definitions on the concepts of benefits and risks and no formal guidance on the process of their balancing. As a result, interviewees, between agencies and within the same agency, expressed divergent views on the meaning of benefits and risks, and on their weighing," said the report.
In all six agencies, none of the interviewees mentioned using a validated and structured process for assessing benefits and risks; however, most acknowledged the need for a more systematic approach and the value it can add.
"The benefit-risk balance is generally considered as the most difficult part of the assessment process, even for experienced assessors. It was mentioned that the most challenging situations are those in which there is substantial uncertainty about the benefits and the risks of a product, the products belong to a new class of drugs, or the products belong to the therapeutic area of oncology," said the report.
The project team has suggested that the current process for evaluating benefit–risk can be improved by establishing commonly agreed definitions for benefits and risks, which may help to structure assessment and facilitate communication throughout different levels of the regulatory process.
The team also suggests separating the type of effects that derive from the use of a pharmaceutical product, and the uncertainty surrounding these effects. To assist this, the team proposes a four-fold qualitative model that separates favorable effects; uncertainty of favorable effects; unfavorable effects; and uncertainty of unfavorable effects. This model has already been incorporated into the benefit–risk section of the EMA's Committee for Medicinal Products for Human Use (CHMP) Assessment Report template guidance.
The next phase of the project will examine the applicability of currently available tools and processes for regulatory benefit–risk assessment. Three further phases will follow, with the project expected to be fully completed by the end of 2011.