Sunday, September 20, 2009

Case Report Tabulations for The FDA Submission

The Case Report Tabulation (CRT) is the collection of the annotated case report form (CRF), SAS® datasets, metadata, and source programs that comprise a portion of the NDA package submitted to the FDA. The FDA uses it when reviewing submissions. Review starts with the Define document which contains metadata describing the datasets, variables, and values. It is all tied together using internal and external hyperlinks, bookmarks, and destinations to make it easily navigable1.

The CRT is essentially a collection of data and documentation for a study. It contains features such as bookmarks and links to allow reviewers to easily navigate the submission. For consistency, there are guidelines from FDA1 and CDISC defining the components though the guidelines are limited in scope.

We need to create Define Document (define.pdf or define.xml) as a part of CRT.
  • Each dataset is a single SAS transport file and, in general, includes a combination of raw and derived data.

  • Each CRF domain (e.g., demographics, vital signs, adverse events) should be provided as a single dataset.

  • In addition, datasets suitable for reproducing and confirming analyses may also be needed.

  • Patient profiles can also be provided as PDF files

    In 2003, FDA …. Interpreted….. 21 CFR 314.50(f) (1) as defining CRTs to include2:

  • Study Data Tabulations
    Statistical Analysis Datasets
    Data Listings
    Patient Profiles

    Draft eCTD Guidance: Case Report Tabulations

    Data tabulations ___Data tabulations datasets ___Data definitions

  • Data listings ___Data listing datasets ___Data definitions

  • Analysis datasets __Analysis datasets ___Analysis programs ___Data definitions

  • Subject profiles

  • IND safety reports

Data Tabulations:

  • Data tabulations are datasets in which each record is a single observation for a subject.”

  • Specifications are located in the Study Data Tabulation Model (SDTM) developed by CDISC at *Each dataset is provided as a SAS Transport (XPORT) file.
Data Listings:

  • “Data listings are datasets in which each record is a series of observations collected for each subject during a study or for each subject for each visit during the study organized by domain.”

  • Currently, there are no further specifications for organizing data listing datasets.

  • General information about creating datasets can be found in the SDTM implementation guides referenced in the data tabulation dataset specifications.

  • Each dataset is provided as a SAS Transport (XPORT) file.
Analysis datasets:

  • “Analysis datasets are datasets created to support specific analyses. Programs are scripts used with selected software to produce reported analyses based on these datasets.”

  • Each dataset is provided as a SAS Transport (XPORT) file.

  • Programs should be provided as both ASCII text and PDF files and should include sufficient documentation to allow a reviewer to understand the submitted programs.

  • It is not necessary to provide analysis datasets and programs that will enable the reviewer to directly reproduce reported results using agency hardware and software. Currently, there are no other additional specifications for creating analysis datasets.
Subject Profiles:
  • “Subject profiles are displays of study data of various modalities collected for an individual subject and organized by time.”

  • Each individual patient’s complete patient profile is in a single PDF file or a book-marked section of a single PDF file for all patients.



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