Key Changes in Benefit–Risk Assessment Guidelines and Implications for Data Analysis in Drug Development

ABSTRACT

The number and complexity of regulatory and legislative policy initiatives for benefit–risk (B-R) assessments and the challenges associated with operationalizing and integrating these initiatives in the drug development process have increased exponentially in the last 10 years. Although there are some similarities in the approaches being used among regions, there are no unifying principles for a consistent approach to address various regulatory agency requirements. Therefore, some sponsors might end up with marketing authorization in one region but not in another, in spite of using the same available benefits and risks evidence without obvious differences between regions. Fortunately, however, there has been a recent global effort by the International Conference on Harmonization (ICH) to develop guidance which provides greater specificity on the format and structure of B-R evidence that is submitted with marketing applications in Module 2 of the Common Technical Document (CTD). The guidance was finalized in June 2016.

This article highlights some of the more notable proposed revisions to the ICH guidance for the B-R conclusions (Section 2.5.6) that was recently made public and some germane points to consider, particularly as it relates to effort to minimizing uncertainties associated with the B-R assessment. The discussion speaks to the dynamic nature and attendant imbalances between the pre- and post-market settings in the sources, timing and nature of the information we collect on favorable (benefits) and unfavorable (risks) effects of medicinal products, characterization of these products' attributes including the emerging role of patient input in product development, and the need to better integrate clinical trial findings and real-world clinical data to enhance our understanding of the expected performance of medical products in the intended patient population.

KEYWORDS:

• Patient perspectives
• Personalized benefit-risk
• Risk characterization

Grant Support/Conflict of Interest Statement

The authors are employees of Merck & Co and have not received any grants to support this work, nor have any conflict of interest to declare.

Notes

1 For purposes of this article, the words benefits refer to favorable effects and risks refer to unfavorable effects of a product.

2 For purposes of this article, the words “product” and “drug” are used interchangeably and refer to medicinal products, including drugs, biologics, and/or devices.