 This website had its origins in the difficulties encountered when the authors asked the question "what are the consistent and well defined and accepted methods used to make the most most fundamentally important assessment of a drug's benefit-risk balance (BRB)?"
When regulatory agencies were asked what quantitative methods are available to use to provide an acceptable assessment of the benefit-risk relationship, the answer was "we don't know of any" or "there are no validated methods". Nonetheless, this assessment is pivotal to addressing whether or not patients are likely to receive benefits from treatment with a therapeutic that outweigh the observed risks. One of the reasons for having regulatory bodies is to ensure that this most fundamentally important assessment is performed consistently for all drugs and that patients are protected against unacceptable risk. The data gathered throughout the course of a therapeutic's development is ultimately for the purpose of addressing the relationship between risks, side effects/adverse events, and the benefit(s) permitting assessment of the BRB at key milestones and for the determination if a therapeutic is marketable.
In situations where the beneficial affect(s) is large and readily quantified and the side effects are minor in nature, the use of sophisticated quantitative tools is generally not required to assess if benefit outweighs risk. However, when there are significant side effects and/or the presence of serious adverse events, or there are significant side effects and the beneficial effects may be small or relatively minor in nature, more quantitative/accurate assessment of the benefit-risk balance is much more important. This can be critical to protecting patients against exposure to unnecessary risks and the development of effective risk mitigation strategies and plans.
The potential degree of complexity of the benefit-risk balance assessment is not widely appreciated and readily exceeds current qualitative approaches. The complexity of this assessment, even when we consider only 20 adverse outcomes, is overwhelming and simply impossible to deal with in a purely qualitative manner. When the vectors describing these outcomes are not co-linear and we take into consideration possible intersections, the analysis of 20 events involves more than 1,000,000 comparisons.
The importance of BRB assessment is not limited to the final assessment of a potential drug/therapeutic, this actually occurs at key points throughout the development process. Perhaps the more critical and sensitive case is that of a prospective treatment that requires study under the exception of informed consent for emergency medicine, such as in prehospital treatment of heart attacks or trauma. These trials are permitted to go forward based upon the assessment that the benefit outweighs the risk for these patients. However, performing trials under these controversial and extraordinary circumstances requires the highest level of critical assessment of the prospective benefit-risk balance.
Situations like this cry out for some sort of universal index, such as the putative benefit-risk ratio, to bring reliability, interpretability, and consistency tothis process across different therapeutics and different clinical settings. It is the recognition of this most fundamental need that has motivated the authors to establish this website with the goal of facilitating efforts to achieve this goal.
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