Specific Safety Monitoring Tools & How This Will Benefit Drug Safety Jim Buchanan, PharmD Covilance LLC

Safety Evaluation Toolkit Methodology Guidance FDA Pre-Marketing Risk Assessment FDA Good Pharmacovigilance Practices and Pharmacoepidemiology FDA Reviewer Guidance Proprietary Tools Spotfire, JMP, Qlik, Tableau, J Review, etc. Open Source Tools CTSPedia, Rho Safety Monitoring

CTSPedia https://www.ctspedia.org/do/view/CTSpedia/StatGraphHome

Rho Safety Monitoring http://resources.rhoworld.com/blog/an-interactive-suite-of-data-visualizations-for-safety-monitoring

Next Generation Safety Tools Desired Features Interactive functionality Open source Provide a workflow to cover essential analyses Base the analyses in established science

ASA-DIA Biopharm Safety Working Group Workstream 1b: Safety Evaluation and Identification of Risk Identify common safety questions Develop interactive signal detection and evaluation tools Make available to drug safety/pharmacovigilance departments, safety assessment committees, data monitoring committees, regulatory authorities Provide training to support the adoption and efficient use of the tools

ASA-DIA Biopharm Safety Working Group Initial Safety Topics to Target: Hepatotoxicity QT prolongation Adverse event evaluation

Interactive eDISH plot – Design Principals Free and Open Source – GitHub Repo1 – Demo Page2 Leverage existing clinical data standards (AdAM, SDTM) Graphics created with standard web technology (javascript, html, css) Minimal dependencies (d3.js3, webcharts.js4) Planning to release an R package with shiny and htmlwidgets, but graphics can work on many platforms. 1 https://github.com/ASA-DIA-InteractiveSafetyGraphics/safety-eDISH 2 https://asa-dia-interactivesafetygraphics.github.io/safety-eDISH/test/ 3 https://d3js.org/ 4 https://github.com/RhoInc/Webcharts

Interactive eDISH plot – Population View 2 Overview Interactive eDish plot with one point per participant showing maximal ALT and TB over the course of the study. Features eDish Scatter plot Interactive Grouping sets point color Toggle between eDish, mDish and absolute measures Interactive cut points with linked summary table Option to set point radius based on 3rd measure Choose Linear or Logarithmic axes Fill points based on timing of peak values Interactive filters Chart reset Marginal box plots distributions Hover on a point to see exact values Click a point for participant details view 10 2 3 4 1 11 5 6 10 7 4 8 9

Interactive eDISH plot – Participant View Overview Click a point to see details for a selected participant. Features Plot showing participant’s lab values across visits Participant details section with demographic summary and optional link to external participant profile Longitudinal Plot of key lab values vs upper limit of normal Lab summary table with spark lines 1 2 3 4