This last year has been marked by new standards, industry templates and initiatives, and regulatory guidance — an intense year for Clinical Data Standards Development.

And it can certainly be challenging for sponsors to keep up with the evolving landscape: Standard Development Organizations (SDOs), such as the CDISC, advanced clinical data standards; regulatory agencies like the FDA added specific requirements; and industry initiatives such as PHUSE worked to clarify and address different stakeholders’ expectations through the development of white papers.

Here I provide a quick summary of what was released in the year we have just left behind.

Regulatory guidance

While the industry awaits the EMA’s long-anticipated clinical data standards submission requirements (see the current status of their pilot project here), the FDA celebrated the 10th anniversary of its Study Data Conformance Guide last April. If you missed it, check out my previous post “New FDA Data Submission Requirements and Substantial Changes,” which discussed a decade of guidance improvements and the latest requirements. Since then, the FDA has released two new versions of its Clinical Data Standards Guidance. These updates do not introduce major new requirements other than confirming that SDTM and ADaM Medical Devices IG for both CDER and CBER FDA divisions “align with FDA current business needs.”

It’s also worthwhile to mention the recent release of the FDA’s Protocol Deviations for Clinical Investigations of Drugs, Biological Products, and Devices. The guidance provides various recommendations around the management of protocol deviations, including some specific recommendations for SDTM mapping, such as including a variable in the DV domain that provides the sponsor’s determination of whether the protocol deviation was important. See also my friend Eanna Kiely’s LinkedIn post.  

CDISC standards

While continuing to advance initiatives aimed at full clinical trial study data digitalization with for example the release of the third version of the CDISC USDM (CDISC Unified Study Data Model), throughout 2024, CDISC continued to release new standards, update existing ones, and advance cross-industry initiatives such as CDISC CORE.

Notable examples of new releases in 2024 include the first version of the CDISC Analysis Results Standard, aimed at providing a framework for linking analysis results directly to the data and metadata that support them. Several presentations and workshops were held at various events over the past two years to promote first the idea and then gather feedback from the audience prior to its final release last April.

Later in the year, similar to the eCRF Portal, an eTFL Portal was also released. This resource includes examples of the most common analysis table layouts, complete with table shells, input ADaM datasets, define.xml, and the JSON version of the analysis results along with metadata. While not a regulatory requirement, this standard adds an important missing piece in our industry’s “dream” end-to-end goal.

It is also worth mentioning the first version of the CDISC Tobacco Implementation Guide (TIG), developed in collaboration with the FDA’s Center for Tobacco Products (CTP). This guide aims to assist tobacco companies in implementing CDISC foundational standards, such as CDASH, SDTM, and ADaM. If you are working at a Tobacco company, check also the recent launched TIG eSubmission Pilot.

Other highlights include updates to existing standards and new resources added to the CDISC Library (see the full list of resources here). Regular updates to CDISC Biomedical Concepts also became a key focus of the CDISC Library.

For a look ahead, check out the CDISC Standards Timeline for 2025.

Industry initiatives

PHUSE continued its work through dedicated Working Groups (WGs) focused on Optimizing the Use of Data Standards. In addition to maintaining a peer-reviewed QA for SDTM ADaM Implementation, these WGs have released two White Papers (WPs) summarizing the Data Standards challenges, nowadays and looking ahead with new trial designs, and how companies implement and govern Data Standards.

Both WPs are based on the outcomes from two surveys conducted during the 2022 and 2023 PHUSE Computational Science Symposium (CSS), with the second one in particular proposing some potential governance best practices across the industry aiming to establish some implementation consistency across companies. It’s worthwhile to mention that these WPs share that about 50% of respondents “affirmed” they do not have a dedicated data standards team or were unaware if one existed in their company. Among those with data standards teams in place, there was significant variation in structure, ranging from cross-functional groups to teams focused on specific functions. Only a few centralized teams addressed topics beyond foundational CDISC standards, such as SAPs and TFL generation. The survey also highlighted that many organizations, more than 50%, rely on Excel or internally developed tools for managing standards, as commercial metadata repositories (MDRs) are often seen as complex and require long-term investment. These challenges remain consistent across pharma, biotech, and CROs.

Applying CDISC standards to non-interventional studies and real-world data continues to be a challenge due to diverse data sources and scenarios, such as the use of external control arms. This was clear when I had the opportunity to host a CDISC ADaM training at one company in Europe specializing in Observational Studies.

The release of the CDISC Considerations for SDTM Implementation in Observational Studies and Real-World Data v1.0 in February addressed some of the SDTM mapping issues. Similarly for the previously released PHUSE Data Standards for Non-Interventional Studies, which covers additional ADaM-related topics, the FDA Data Standards for Drug and Biological Product Submissions Containing Real-World Data guidance (December 2023) provided some initial recommendations when submitting data packages including real-world data.

With the release of the first version of the CDISC Dataset-JSON in 2023, the long-awaited alternative to SAS XPT as a standard for data submission took a significant step forward. Following the release of the first version, in collaboration with the FDA and CIDSC, PHUSE completed a pilot project in 2024, with a full report made available last June. Last December, CDISC released an updated version (1.1) of the standard. Among recommendations from testers, some bugs were detected, for example, when importing or exporting to SAS, which includes some known differences between software such as SAS and R with numeric precision and date representation, or limitations requiring updates to analytics tools used by the FDA (e.g., SAS JMP). Details of the changes implemented or items rejected from the public review can be found here.

In 2024, open source continued to be a leitmotiv in our industry, with tools and initiatives aimed at regulating the use of open-source solutions in clinical data submission (see also Cytel blog “The Journey into Open Source So Far”). Also, check the progress of industry initiatives such as CDISC COSA.

Furthermore, the Using R to Submit Research to the FDA initiative completed the first part of its final Pilot 4. While the focus of the three previous pilots was on demonstrating that SDTM and ADaM packages could be created and submitted to the FDA using R — including packages that might include Shiny applications for reviewers to use — this pilot explored the use of novel technologies such as Linux containers and WebAssembly to bundle a Shiny application into a self-contained package, facilitating a smoother process of both transferring and executing the application, allowing agency reviewers to easily run and evaluate software without complex setups.

New releases and updates from 2024

See below a complete list of new releases and updates that occurred in 2024 with links to individual resources. Do not hesitate to spot any missing items!

February

• CDISC Considerations for SDTM Implementation in Observational Studies and Real-World Data v1.0

March

• FDA Bioresearch Monitoring Technical Conformance Guide v3.1 (Minor Language Update)

April

• CDISC USDM v3.0
• CDISC Analysis Results Standard v1.0 and eTFL portal
• PHUSE Data Standards White Paper
• PMDA Revision of Technical Conformance Guide on Electronic Study Data Submissions

June

• CDISC Tobacco Implementation Guide v1.0
• PHUSE Dataset-JSON as Alternative Transport Format for Regulatory Submissions: Final Pilot Report
• FDA Standardized Format for Electronic Submission for Marketing Applications Content for the Planning of Bioresearch Monitoring (BIMO) Inspections for Center of Biologics Evaluation and Research Submissions

September

• CDISC Glossary v19.0
• FDA Data Standards Catalog (Latest Release Version 10.4 / September 2024)

October

• PHUSE Best Practices in Data Standards Implementation Governance
• FDA Study Data Technical Conformance Guide – Technical Specifications Document (Latest Release Version 5.9 / October 2024)
• Using R to Submit Research to the FDA

December

• CDISC USDM v3.0 Conformance Rule Specifications
• CDISC Define-XML v2.1.8
• CDISC Dataset-JSON v1.1
• CDISC Controlled Terminology Relationships v1.0 for SDTM v1.7, SDTMIG v3.3, SDTMIG-MD v1.1
• CDISC Duchenne Muscular Dystrophy Therapeutic Area User Guide v1.0 – Cardiac Imaging Supplement
• CDISC Biomedical Concepts (Latest Release 2024-12-16)
• FDA Protocol Deviations for Clinical Investigations of Drugs, Biological Products, and Devices

Interested in learning more?

Download Angelo Tinazzi’s new ebook, “The Good Data Submission Doctor on Data Submission and Data Integration to the FDA”:

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