Background

This page contains some useful information and references for anyone working in the pharmaceutical industry and looking to use R in a regulatory context.

FDA

As described in the R Foundation’s guidance document, there are several import documents / statements available form the FDA:

“FDA does not require use of any specific software for statistical analyses, and statistical software is not explicitly discussed in Title 21 of the Code of Federal Regulations [e.g., in 21CFR part 11]. However, the software package(s) used for statistical analyses should be fully documented in the submission, including version and build identification. As noted in the FDA guidance, E9 Statistical Principles for Clinical Trials (available at http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm), “The computer software used for data management and statistical analysis should be reliable, and documentation of appropriate software testing procedures should be available.” Sponsors are encouraged to consult with FDA review teams and especially with FDA statisticians regarding the choice and suitability of statistical software packages at an early stage in the product development process.”

“Sponsors should provide the software programs used to create all ADaM datasets and generate tables and figures associated with primary and secondary efficacy analyses. Furthermore, sponsors should submit software programs used to generate additional information included in Section 14 CLINICAL STUDIES of the Prescribing Information (PI)26 if applicable. The specific software utilized should be specified in the ADRG. The main purpose of requesting the submission of these programs is to understand the process by which the variables for the respective analyses were created and to confirm the analysis algorithms. Sponsors should submit software programs in ASCII text format; however, executable file extensions should not be used.”

R Foundation

In March 2018, the R Foundation re-released a document entitle R: Regulatory Compliance and Validation Issues. A Guidance Document for the Use of R in Regulated Clinical Trial Environments. This document describes the R Foundation’s response to ICH and FDA guidelines with regards to the ‘Base’ and ‘Recommended’ R packages.

Accompanying the guidance document the R Foundation have also released details of the R Development Core Team’s Software Development Lifecycle.

The contents of this document is summarized here.