FDA Data Standards for Regulatory Submission

The FDA has released a position statement on study data standards for regulatory submissions. According to recent legislation in the U.S., the FDA “will develop guidance for the industry on the use of CDISC data standards for the electronic submission of study data in applications”. The statement goes on to say that the FDA will publish guidance that “requires study data in conformance to CDISC standards”.

CROS NT discusses adopting and implementing CDISC standards as well as preparing a project mapping plan with your CRO.

Conversion to CDISC standards generally includes SDTM (Study Data Tabulation Model), ADaM (Analysis Data Model) and CDASH (Clinical Data Acquisition Standards Harmonization). It is important to start implementing CDISC standards during data collection by having Data Managers design the CRF using CDASH standards. This makes the process of mapping data into SDTM and ADaM datasets much more straightforward.

However, there are many legacy studies with valuable data that have not been conducted to this standard. This can create issues when trying to integrate data from different studies. To correct this problem it often requires considerable mapping work which can be expensive.

When requesting a CRO or an internal team to map a set of legacy studies to CDISC standards, requesting the following deliverables will ensure a structured and validated approach:

  •  Project Plan and Project Charter to establish contacts, timelines, frequency of status reports, project risks and issue resolution procedure.
  • Standardized Data using SDTM format, including the source of the original data (specify version of SAS to be used)
  • Mapping documents between the source and target data, to provide traceability information
  • Data Status Table containing the different source data characteristics including quantitative and qualitative measurements
  • Metadata File (define.xml)
  • Mapping Program files and execution logs (.log) which documents the mapping process
  • Reviewers Guide which contains a detailed description of the mapping rules and source data types for each study
  • Validation Certificate containing signed reports of quality control checks including resumes of the personnel involved

Using CDISC standards can ensure much better traceability of data, especially in cases where there is one global data warehouse. The statistical programming team prepares ADaM datasets for both traceability and analysis-ready requirements. Analysis-ready datasets, according to CDISC “ADaM Implementation Guide Version 1.0”, means minimal programming is required and no derivations should be done during programming of the statistical analysis but all variables and observations should be included in the dataset.

Implementing CDISC standards means adopting technologies that can manage the flow of data and information. Keeping clinical data in multiple repositories can create a complex management process and is often prone to error. Setting up a central database for all data – whether from a laboratory, a CRF or an ePRO device – to be stored in one place, allows for an easier mapping process.

CROS NT and CDISC Mapping

CROS NT is a CDISC Gold Member, meaning it has constant access to new data standards and new documentation regarding CDISC standards. CROS NT has helped many companies incorporate CDASH, SDTM and ADaM standards into their organizations and mapped legacy studies to create the necessary consistency in formats. The programming team has developed some excellent macros to reduce time, costs and ensure consistency.

In a recent vaccine study, CROS NT applied CDISC standards for an integrated summaries submission to the FDA. This involved creating an annotated CRF, implementation of data structures within SAS, and creating a global database structure. Following initial consultancy to discover a Sponsor’s needs, CROS NT can offer:

  • Mapping of raw data to SDTM and ADaM standards
  • CDASH libraries to provide competitive EDC usage fees
  • Macros/tools to ensure fast and accurate mapping
  • Data repositories with flexible data access and reporting capabilities
    CROS NT has also provided consultancy on CDISC mapping in various studies including a Phase III oncology study and a Phase IV respiratory study.