The motivating publication:
UPDATE: Successful R-Based Package Submission with Shiny Component to FDA
By R Consortium, 07 December 2022
Good news arrived in last December: An R-based package with a Shiny Component was successfully completed to the FDA.
If you are not familiar with the above abbreviations that means that you are not involved in Clinical Research in the Pharma Industry. I’m sorry to say but in that case you are maybe less enthusiastic to hear this.
Before explaining the importance of this pioneer step, it should be mentioned that a maybe more revolutionary step was taken December 2021, when the first R-based package was submitted to the FDA successfully ( https://www.r-consortium.org/blog/2021/12/08/successful-r-based-test-package-submitted-to-fda ).
Going back to the current announcement: what happened and what does it mean?
R is a computation framework with its own programmatic language and a really huge number of supportive tools (roughly 20,000 so-called packages). While SAS (Statistical Analysis Software), another program is the dominant and preferred tool to analyze results of Clinical Trials, it was already admitted by the FDA that R can be a valid equivalent to SAS already in 2012. /Link? /. Nobody questions that valid results can be derived with R (core) programs. But there is a big temptation to use further supportive tools – e.g. for string management – which validation status might be unclear.
R is aware of this problem and they issued a document (“R: Regulatory Compliance and Validation Issues A Guidance Document for the Use of R in Regulated Clinical Trial Environments”) in 2021 to prove the 21 CFR Part 11 compliance of R ( https://www.r-project.org/doc/R-FDA.pdf ). Some experts are still skeptical about the correctness of these arguments (link?) while others already use R in analysis and reporting of clinical trials ( https://www.pharmasug.org/proceedings/2021/AD/PharmaSUG-2021-AD-079.pdf ).
This is the step when I have to place the R Consortium ( https://www.r-consortium.org ) in the picture. R consortium is for “…to work with and provide support to the R Foundation and to the key organizations developing, maintaining, distributing and using R software through the identification, development and implementation of infrastructure projects.”
Within the R consortium you can identify several Working Groups, including the R Submission Working Group ( https://rconsortium.github.io/submissions-wg/ ). The result they achieved can be seen here ( https://rconsortium.shinyapps.io/submissions-pilot2/ ) in the format of an R Shiny application (Shiny in short is responsible to convert any type of input to a menu-driven HTML output). As they stated the original goal was to “While the intent of the project is to enable execution of the Shiny application in a reviewer’s local R environment, a deployed version of the application is available in open access through the Shinyapps.io service“.
Not only is the fact important that a Shiny application, a web-based documentation, was successfully submitted. It is also important that this activity was performed within a non-profit framework – in harmony with the original R concept – and all the documentation is clear, transparent and available for free of charge at ( https://github.com/RConsortium/submissions-pilot2-to-fda ).
The authors created a demo eCTD package following the ICH guidance.
Good luck to enter into the world of web-based, real time analysis and reporting of Clinical Trials!
