- An update from PHUSE Data Visualization Project

Interactive Analysis for Decision Making & Submissions

Co-leads of PHUSE project team: Xiangyun (Sharon) Wang, Zachary SkrivanekCo-leads of internal Lilly FDA pilot group: Mary Nilsson, Zachary SkrivanekCo-leads of internal Genentech FDA pilot group: Doug Kelkhoff, Xiangyun Wang

Outline

• Background and Goals of Working Group• Approaches Considered• POC & Pilot• Next Steps

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BACKGROUND AND GOALS OF PROJECT TEAM

Interactive Data Visualizations for Decision Making in Submissions

Drug Submission Process

“Reliance On ‘Digitized Paper’ Is Slowing Drug Development” – Janet Woodcock, director of CDER

Interactive Analysis A Paradigm Shift

Potential Application Areas: DSUR*, PMP*, DSR*, CSR* =ongoing

Sponsors • Leverage agility of

interactive analysis approach for quick insights and guided analysis

• Streamline process from exploratory to decision-making and filing

Efficiency

<

Speed

<

Agility

FDA• Perform effective review of

the submitted data and analysis

• Conduct additional exploratory analysis as needed

Effective interactions, fast drug approval, more and better drugs to patients

<

Interactive Analysis POC Proposal

Goal Explore the feasibility and benefits of interactive analysis approach for regulatory deliverable

What

Sponsor (Pharma company):• Develops an interactive analysis for a submission task such as a Pre-Meeting

Package, an eSub filing package• For the purpose of pilot, the interactive package is provided in addition to the

traditional package using SAS

FDA reviewers :• Accesses the interactive analysis tool via web browser

APPROACHES CONSIDEREDInteractive Data Visualizations for Decision Making in Submissions

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Our Proposal: Interactive Analysis Roadmap

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Current Status Transformation Stage Future Status

eSub with static data displays

eSub with embedded

interactive data displays

eSub+

shared interactive tools as reviewing

aid

eSub for core results

+ shared interactive

tools

Real time review enabled by

shared interactive tools

Pilot 1 Pilot 2

PhUSE Data Visualization Working Group

Pilot 3

Best Practice for Interactive Analyses in Submission

Our delivery: A white paper to share with the industry including• Scope of use • Validation • Traceability and Reproducibility • Methods to share the interactive analyses with the FDA• Learning from the pilots: FDA requirements, process on how• Misc.

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Approaches considered1. Give FDA access to webserver (e.g. for Spotfire, R Shiny, etc..)2. FDA hosts platform (e.g. for Spotfire, R Shiny, etc..)3. 3rd party server (e.g. for Spotfire, R Shiny, etc..)4. Submit containerized app and FDA hosts on virtual machine5. Submit an app and the FDA installs it and runs in internally6. Stand-alone HTML interactive display as part of submission

package

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POC & PILOT I:ESUB WITH EMBEDDED INTERACTIVE DATA DISPLAYS (ELI LILLY)

Interactive Data Visualizations for Decision Making in Submissions

3/13/2011

Co-leads of internal Lilly FDA pilot group: Mary Nilsson, Zachary Skrivanek

• eCTD submission• Methods• Contents– Cover letter– Fake CSR– Fake volcano plot– Fake animation

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Proof of Concept

• eCTD submission• Contents– Cover letter– Summary of Safety– Volcano Plot– Two 29 page tables

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FDA Pilot

• 78 page table

Pilot

POC & PILOT II: DOCKER POC WITH R SHINY BASED INTERACTIVE TOOL (GENENTECH)

Interactive Data Visualizations for Decision Making in Submissions

3/13/2015

Genentech internal working team:Nilesh Narayan (Regulatory), Doug Kelkhoff (Programming), Xiangyun Wang (Programming)

• eCTD submission• M5 structure• Contents– Cover letter– Docker script file– R Shiny demo app– Reviewers’ guide

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Proof of Concept

• Missing Reviewersguide.pdf• Encountered a roadblock due to FDA security concern during

the initial POC when installing R package library in a local driveèA second iteration is in progress by

• Redesign to install R package library within the container to avoid security issue • Restructure to improve workflow for shared package library among multiple interfaces

including analytical and visualization portals

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PoC Feedback from FDA

• eCTD consideration – Submit R packages using “.r” file extension vs. “.R” per R coding best

practice, unless the eCTD can be relaxed to allow uppercase letters.

• Early collaboration with FDA staff is critical – How to design the submission package with ease of use in mind for

reviewers?

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Learning from PoC Project

NEXT STEPSInteractive Data Visualizations for Decision Making in Submissions

Future Pilots20

• Genentech will conduct a real submission pilot via Docker containerization in 2020 assuming that the technical POC works well from FDA side

• Lilly will pilot more regulatory interactions with the inclusion of interactive displays to enhance information sharing

Call for industry participations

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Acknowledgement22

PHUSE Best Practice for Interactive Analysis Project Team:Industry: Raj kiran Boddu (Takeda)Phil Bowsher (Rstudio)Karl Brand (Bayer)Maria Dalton (GSK)Josephine Fong (Genentech) Eric S. Herbel (I-Review)Doug Kelkhoff, (Genentech)Mary E Nilsson (Eli Lilly)Catherine Xia (Gilead)James Kim (Pfizer)

FDA: Paul SchuetteAlan Shapiro