A Whole New (Open) World

Insights from R-based Submission Pilots

Eric Nantz

Statistician / Developer / Podcaster

Eli Lilly & Company

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R/Pharma 2018

I saw firsthand the potential of such a collaboration with the advent of the R/Pharma conference. Keynotes by Joe Cheng (Using Shiny Reponsibly in Pharma) and Paul Schuette (Using R in a Regulatory Environment). Also the genesis of key initiatives such as the R Validation Hub and the Pharmaverse

R Consortium

The R Consortium is a non-profit organization with the mission to support the:

• R Language
• R Foundation
• R Community

The R Consortium Provides:

• Grants to extend the technical and social infrastructure of the R Ecosystem
• Oversight and governance for working groups that enable industry and government collaboration
• An open forum for the R Community

R Submissions Working Group

• Industry and Regulatory members
• Create submission deliverables with open-source software
• Emulate realistic submission review
• Innovation encouraged!

Foundation - Pilot 1 Submission

• November 2021 - Successful R-based Test Package Submitted to FDA
• Adhered to Electronic Common Technical Document (eCTD) specifications
  • Analysis Data Reviewer Guide
  • R Package converted to text file using {pkglite}
  • ADaM datasets
  • TLF output

Many Results

In the not-so-distant past, the results of a clinical trial were sent to reviewers as paper outputs that could fill a small moving truck

Time to comb through many static outputs. How many outputs are there total? Over 1,000 tables, listings, and graphs.

With Great Power…

• Dynamically updates p-values based on filtered observation
• Potential for confusion and misinterpretation
• Compromise: Allow filtering within visualization module only

Install & Execute Application

• Extract submission bundle
• Install R
• (Optionally install RStudio)
• Install Rtools for package compilation
• Install {renv} R package
• Install application package library
• Run application in R process

Install & Execute Application

• Extract submission bundle
• Launch App in web process
• View App in web browser

Shiny

Web-Assembly

Docker

Docker Container: Start your Engines

• Encapsulate Pilot 2 Application code

• Build container using Dockerfile.txt

• Run container in separate process

• Launch web browser

docker build \
  --build-arg LOCAL_DATA_DIR=datasets \
  --build-arg LOCAL_APP_DIR=pilot2wrappers \
  -t RConsortium/submissions-pilot4-container:latest \
  -f Dockerfile.txt .

docker run \
  -it \
  --rm \
  -p 8787:8787 \
  RConsortium/submissions-pilot4-container:latest

WebAssembly: Small Tune-up

• Verify packages compatibility with WebR

  • {golem} {rhino}

• Augment shinylive::export to inject SAS data sets

• User-friendly wrappers

• Launch web browser

source("utils.R")
build_app()
run_app_webassembly()

The Extra (Virtual) Mile

Racing to the Final Lap 🏁

June 2025: Transfer Pilot 4 submission packages to FDA

• {pkglite} to assemble text file bundle
• Long term: Use .zip archive format

Up Next: Pilot 5 Dataset-JSON format

Future Pilots Under Consideration

• Large-scale simulated clinical data
• Reproducible submission environment using Nix
• Generative AI to aid ADRG development

Acknowledgements

• Sam Parmar (Pfizer)

• Ben Straub (GSK)

• Robert Devine (J&J)

• Saghir Bashir (Argenx)

• Ning Leng (Roche)

• Pedro Silva (Jumping Rivers)

• André Veríssimo

• Vedha Viyash

• Pawel Rzymkiewicz (OlympCode)

• Paul Schuette

• Hye Soo Cho

• Youn Kyeong Chang

Thank You!

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