Are Interactive Graphics in a DMC Ready for Prime-Time for Better Safety Reviews? James Buchanan, Pharm.D

The Challenge Pages of data outputs to sort through…

The Challenge Summary displays lack details…

The Inspiration Improve upon existing static data visualizations by adding interactive features to: Be able to filter on various data elements Choose additional data to expand the visualization Drill down to subject level data

The Inspiration Create interactive graphics to address principal safety issues of interest: Liver toxicity QTc prolongation Nephrotoxicity Bone marrow toxicity Drug-drug interactions

The Goals A creative effort from the DIA/ASA Biopharm Working Group to develop a tool that: Open-source – free to all users Easy to use web-based application Data format agnostic – ADaM & SDTM, but also other common formats Easily configurable Encourages collaboration between clinicians and statisticians Applicable to industry, regulatory authorities, DMCs and academic communities

The Tool Pair an interactive graphic with a clinical workflow to guide evaluations based on the medical literature.

The Tool Pair an interactive graphic with a clinical workflow to guide evaluations based on the medical literature.

Pilot Test Results 15+ Testers from 8 Organizations FDA, Merck, Novartis, BI, Bayer, Abbvie, Lilly, J&J, Rho All users reported than the tool met or exceeded expectations None found it difficult to upload data using the R package ~50 specific comments / requests Several teams working on pilot deployments

2019 Road Map V1.0 release (June 2019) Add study drug treatment history in V1.1 (Summer 2019) Add a full participant profile (Fall 2019) AE, concomitant medications, narratives, etc. 2019 Presentations FDA Innovation Forum PHUSE Connect World Drug Safety Conference DIA short courses & multiple sessions Midwest Biopharmaceutical Statistics Workshop Rstudio Conference RPharma Conference

Technical Improvements Future Development New Safety Domains New Charts and Workflows for: Nephrotoxicity QTc Prolongation Volcano Plot Explorer Recurrent AEs Technical Improvements Easy communication between charts Embedded access to clinical workflows within the shiny app Optimized graphics for studies with very large data sets Facilitated “real-time” statistical analysis Formalized Maintenance Model

Lessons Learned Feedback and experience with the first tool suggests… Collaboration between clinicians, statisticians and programmers is a powerful combination of skills Open source tools with a medically supported workflow is a platform that has the potential to be a new lingua franca for safety evaluations Evolution of the tool across companies has already started organically Partnerships across industry can address a common need while reducing internal company resource expenditures to create and maintain custom tools (the interactive tools speak to a larger business need)

Availability https://safetygraphics.github.io/ Jim Buchanan jbuchanan@covilance.com