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In the last decade, a number of initiatives to define good practices for projects involving modeling and simulation have been put forward. No proposal for best practice in modeling and simulation, however, has been generally and consciously adopted in the pharmaceutical world. This perspective aims to highlight these recent proposals (Marshall et al., 2016; O'Kelly et al., 2017) with respect to the use of modeling and simulation in the drug development and regulatory approval process. Both groups define Model-Informed Drug Discovery and Development (MID3) inclusively so as to potentially include the whole community of users of modeling and simulation. Applications in both communities (pharmacometrics and statistics) have many similarities in tools and methods to be used for model building, assumption testing, qualification versus available data and sensitivity analysis, albeit with a different focus. Both communities are emphatic that the same good practices could apply across the wide range of mo...

When providing advice on a medical product, a major task for FDA advisory committee members is to determine whether or not the benefits of the product under discussion outweigh its risks. Thoughtful and creative utilization of analysis methods and visualization tools often helps the sponsors and the FDA to clearly and succinctly deliver the key message, that is, whether the benefit-risk profile is favorable or unfavorable. In this article, we summarize a review of analysis methods and visual tools that were included in recent (during 2011–2014) FDA advisory committee meeting materials. We summarize the key findings related to benefit-risk (B-R) evaluations. Illustrative examples of analysis and visualization tools are provided along with potential refinements to provide readers' proper context for the appropriate use of various B-R tools in practice when evaluating the B-R balance of medical products.

Although control for multiplicity is recognized as a cornerstone of proper statistical inference, the topic has rarely been addressed in the specific context of benefit–risk assessment for medical products. This article raises key questions and provides opinions and recommendations. Topics include the symmetry between efficacy and safety endpoints, the proper stage to adjust for multiple endpoints, when and how to adjust for multiple subgroups, when a drug can be approved based on a favorable benefit–risk result in a subgroup, and multiplicity considerations arising from re-analysis of data.