概览
The DIA-ASA Biopharm Safety Evaluation Working Group is developing a series of novel interactive safety graphic tools to enhance the ability of safety and clinical development professionals to identify and evaluate safety signals. Each will be made available as an open-source, non-proprietary application widely available to anyone interested in drug safety evaluation. An open source project like this will likely result in a longer-lasting software solution.
The first tool to be released is designed to explore cases of potential drug-induced hepatotoxicity based on the eDISH plot developed by FDA. Building upon the existing static eDISH plot, the tool allows the user to dynamically adjust laboratory thresholds to account for disease states with elevated transaminase and bilirubin values, modify the time dimension for the occurrence of peak ALT/AST and bilirubin values, account for the extent of alkaline phosphatase elevation, with filters for treatment assignment, gender, race and age group. Cases that appear in the potential Hy’s Law, Temple’s corollary and hyperbilirubinemia quadrants can be individually explored to detail the time course of changes in various analytes, and assess the concurrence with adverse events and the exposure to concomitant medications. In order to assist the safety reviewer, a workflow is provided to guide the user through the recommended analyses, using the features of the tool, for each of the quadrants of interest. The workflow is based on evaluations supported by expert hepatologists and the medical literature.
The short course will demonstrate the functions of the tool by way of case examples exploring various hepatotoxicity signals. Prior attendees of the DIA Advanced Signal Detection course will find this course builds upon the concepts presented in that course, but it is not a prerequisite for attending this class. In addition, information will be provided on how attendees can implement this RShiny/JavaScript tool in their organizations.