Are we moving away from data listings now that the standard data sets (such as CDISC-compliant SDTM and ADaM data sets) are mandated by FDA?

After a clinical trial is concluded, the statistical group (statisticians and statistical programmers) will generate the tables, listings, and figures (TLFs in short) for the clinical study report (CSR). If the clinical trial results are good, the CSR including the TLFs and the data sets where the TLFs are generated from will be submitted to the regulatory authorities (such as FDA) for marketing authorization application (such as new drug application (NDA) and biological license application (BLA). 

From the statistical standpoint, the clinical trial is a process to collect the data (demographic, efficacy, and safety). The data sets we collected will be converted and mapped to the standardized format according to the CDISC standards - SDTM for tabulation data sets and ADaM for analysis data sets. The standardized data sets are then used for generating the tables, listings, and figures (may also be called the post-text TLFs). The post-text TLFs will be the building block for constructing the CSRs. 

The data listings are required as part of the CSRs and post-text listings are included in the CSRs as appendices. As specified in ICH E3 "STRUCTURE AND CONTENT OF CLINICAL STUDY REPORTS", data listings will be organized according to the sections/numbers below: 

A data listing will be looking like the below with a listing of adverse events as an example (the mock-up shell). Notice that the listing for adverse events is numbered as Listing 16.2.7 corresponding to the section number indicated in ICH E3 (above).

With the FDA's mandate for submission of the standardized data sets, the CDISC standard tabulation data set is SDTM (study data tabulation model), the natural question is if the data listings are still needed. The data listings are just the simple display of the SDTM data set (or ADaM data set) with format/layout beautified. Some sponsors have moved to the direction of not generating the formal data listings and they think that the CDISC-compliant data sets will be sufficient to replace the data listings. 

According to an FDA Final Guidance Webinar Q&A at Pinnacle21 website, the response indicated that the data listings would be replaced by the standard data sets. 

28: With the advent of a new “misc folder” instead of listings do you think that FDA is getting away from generating listings for each study? It seems that the datasets (SEND, SDTM, and ADaM) would stand alone to support any listings.

Once the standards requirements are in effect, the idea would be that listings would be replaced by the SDTM tabulations data, so yes.

The Final FDA Guidance on Standardized Study Data was initially published December 17, 2014 and has subsequently been revised several times. The FDA Binding Guidance requires Sponsors whose studies start after December 17, 2016 must submit data in FDA-supported formats listed in the FDA Data Standards Catalog. The FDA Data Standards Catalog specifies the use of CDISC standards such as SDTM, ADaM, and Define-XML as well as Controlled Terminology.

FDA has organized or participated in multiple webinars to emphasize the criticality of submitting the data sets in standardized formation, however, there is no subsequent mention about the standardized data sets replacing the data listings. 

I did an informal survey and asked the statisticians and statistical programmers working in other pharmaceutical companies and CROs, almost all responses were that they continue to generate data listings and have no plan to stop generating data listings even though they have been fully compliant with the CDISC data standards for their clinical trials.

Even though the CDISC compliant data sets make the data listings redundant and unnecessary, stopping generating the data listings entirely is a risky approach at this point. The data listings should still be generated until we see FDA's guidance indicating otherwise or until the ICH E3 is revised to indicate that the data listings can be replaced by the standardized data sets. 

Some links to this topic: 

• FDA website: Study Data Standards Resources
• FDA website: Study Data for Submission to CDER and CBER
• FDA Webinar: The FDA Study Data Technical Conformance Guide v4.4 - Nov 22, 2019
• Study Data Technical Conformance Guide - FDACDER Small Business and Industry Assistance (CDER SBIA) Webinar - Study Data Standards in eCTD: What You Need to Know about the New Technical Rejection Criteria - October 12, 2016
• Duke Margolis Center for Health Policy in collaboration with FDA organized a public workshop: Advancing the Development and Implementation of Analysis Data Standard: Key Challenges and Opportunities: