Midwest Biopharmaceutical Statistics Workshop Dynamic SMQ Search for Safety Signal Detection Using Spotfire Xiangyun Wang, Statistical Programming and Analysis Roland Morley & Chen Huang, PD Drug Safety Genentech, Inc. 5/23/2017

Disclaimer All numbers shared in the presentation are based on dummy data. No clinical interpretation should be drawn based on the presentation.

Outlines Background and Objectives Implementation Considerations Dynamic SMQ Search Interface in Spotfire Example Use Case + Demo Summary and Next Step

Smart Together

The Request from Safety Scientists Can we have an interactive approach to SMQ search for ongoing safety signal detection?

The Challenges Current challenges for safety signal detection Manual review with non-standardised groups of terms  prone to error Cross-functional programming support of data retrieval  time consuming with back-and-forth change requests and communication. How to provide a powerful, user-friendly platform to enable effective SMQ search becomes vital in supporting real-time safety signal monitoring in pharmacovigilance

What is SMQ? Standardised MedDRA Queries (SMQs) are groupings of terms from one or more MedDRA System Organ Classes (SOCs) related to defined medical condition or area of interest. SMQ use is recommended as the powerful search strategy to retrieve potential cases of interest for early detection and evaluation of emerging safety signals in clinical development.

Our Approach Goal Empower safety scientists to conduct self-service based on any SMQ(s) of interest for emerging signal detection What Develop an interactive data exploration tool using Spotfire Automate update of all industry SMQs to be consistent with MedDRA version Enable near real-time signal detection with regular data refresh for clinical data via Information Link

Why Spotfire? Ease of use for end-users with its dynamic and flexibility features Stakeholders’ familiarity with the tool Company’s existing Spotfire infrastructure and support team We chose Spotfire as the collaboration tool not only because of its easy-of-use with interactive and dynamic features, but also because of our existing Spotfire infrastructure and stakeholders’ familiarity with the tool.

Implementation Considerations

Database Configuration Master SMQ SMQ ID Preferred Name Description SMQ Version   Study ID Subject ID MedDRA Coded Term MedDRA Version … ADaM AE

SMQ Search Interface in Spotfire Flexibility of search by any SMQ(s) Instantaneously review of summary results Script to help reveal underlying filtered data to ensure accuracy Further exploration capability via filtering Corresponding preferred terms for the SMQ Drill-down into individual patient-level data

Example Use Case What How Leverage ISS Visualization Suite to Support Drug Safety Report (DSR) for Acute Kidney Injury (AKI) How Safety scientists conducted self-exploratory analysis using Acute Renal Failure (wide SMQ) Explore and review subgroup analysis results as needed Work with Biometrics/programming group to finalize analysis to ensure quality and reproducibility

AKI DSR: How the SMQ Search Tool Helped? Safety Scientist leveraged the SMQ search tool to explore many subgroup analysis (~60 outputs) Subset by seriousness, relationship to study drug, standard toxicity grade, Grouping by indication, study treatment, study … Only 12 visualization results needed for final reporting and archiving  List of final outputs with bookmark links in Spotfire:

Summary of Patients with All AKI Relevant AEs

Summary of Patients with AKI Relevant AEs Leading to Drug Withdrawn

Summary of Patients with AKI Relevant Serious AEs

Patient Profile © 2014 DIA, Inc. All rights reserved.

Demo: Dynamic SMQ Search using Spotfire

Benefit Highlights Reproducible signal detection with industry standard baskets of terms Agility with self-service exploration Effectiveness with quick data insights Efficiency gain with time and resource saving

Further Exploration Additional capabilities for safety signal detection: Multiaxiality issue (MedDRA dictionary for secondary paths) Customized search algorithm (e.g. modified SMQ or AE group terms) Streamline the work flow to support from real-time ongoing safety surveillance to decision-making (i.e., compliance considerations)