Standardizing the Benefit-Risk Assessment of New Medicines

Abstract

Pharmaceutical scientists and healthcare professionals participating in the development of new medicines bring important practical perspectives to the evaluation of benefits and risks. Within pharmaceutical companies, these specialists can serve to inform the benefit-risk (BR) assessment process, particularly in the latter stages of drug development. However, pharmaceutical scientists may not be aware of the current state of activity in the ongoing efforts to standardize the BR assessment process. In this article, we discuss the role of BR assessment frameworks, activities that are underpinning the standardization of these approaches, and suggest considerations for pharmaceutical scientists to incorporate these into medicine development programmes, regulatory dossiers and clinician communications. Over the past decade there has been an increasing awareness of the potential benefits that can derive from the use of a standardized methodology to assess and communicate a product’s BR profile. Frameworks (in this context defined as the tools and guidelines for their use to facilitate communication of benefits and risks) being developed by the European Medicines Agency, the Pharmaceutical Research and Manufacturers of America Benefit-Risk Action Team (PhRMA BRAT) initiative and the Centre for Innovation in Regulatory Sciences (CIRS), share a common basis in multi-criteria decision analysis and are introduced in this article. To date, quantitative approaches to BRhave been used cautiously because they have lacked the appropriate sophistication, flexibility, ease of use and ability to communicate BR findings. As a result, while a number of quantitative methods have been developed, none have yet achieved widespread endorsement or adoption. Nevertheless, weighting and valuing the underlying criteria can drive a more visual-based presentation of the results, such as through the use of forest plots. BR criteria can be applied to all stage-gate decisions in the lifecycle of a new medicine. Companies should consider developing a skeletal BR model (one based on a consistently applied BR framework) early in a product’s development cycle by assessing whether the product is likely to meet the minimally acceptable thresholds for benefits and risks based on preclinical data and mechanism of action. This process can be used to identify important areas from which to collect information to narrow gaps in knowledge about the BR profile of the product. BR criteria can also inform phase III go/no go decisions. These criteria are then described within the regulatory application to present data using comparable scales. By using a standardized assessment approach that can easily accommodate the parameters associated with the medicine under development, methods can be designed to help communicate the BR profile to a variety of decision stakeholders.