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U.S. Department of Health and Human Services

Vaccines, Blood & Biologics

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Study Data Submissions to CBER

 Submission of Data in CDISC Format to CBER

Process for Planning and Accepting CDISC SDTM and ADaM

Formatted Submissions in CBER

 

Questions can be directed to CBER CDISC

 

Effective December 15, 2010

SDTM and ADaM are being accepted for CBER IND, NDA and BLA submissions

CBER CDISC Team is the Point of Contact

for all CDISC (Clinical Data Interchange Standards Consortium) related questions


PLANNING

  1. Sponsor/Applicant will obtain the SDTM (Study Data Tabulation Model) and ADaM (Analysis Data Model) Planning Checklist from the link under "Resources for You" on the left side of this page or following links:
    http://www.fda.gov/BiologicsBloodVaccines/DevelopmentApprovalProcess/ucm209163.htm
    http://www.fda.gov/ForIndustry/DataStandards/StudyDataStandards/default.htm
    SDTM and ADaM Submission Planning Checklist Template (DOC - 168KB)
    Example SDTM and ADaM Submission Planning Checklist (PDF - 23KB)
    Example Validation and Data Interpretation Report (PDF - 25KB)
  2. The Sponsor/Applicant should contact the Review Division and notify the RPM (Regulatory Project Manager) of the intent to submit SDTM and ADaM formatted datasets.
  3. The Sponsor/Applicant will complete "the SDTM and ADaM submission planning Checklist Template" and include it in the meeting packet or email to the RPM assigned to the submission.  Any planning meeting can be the forum for these discussions (pre-BLA, end of phase 2, prior to pivotal study, etc.) if there are any questions.
  4. Reviewers and the Sponsor/Applicant will come to an agreement on
    1. The domains identified for the clinical trial study
    2. Variables placed in the SUPPQUAL domain or multiple SUPP--domains
    3. Any custom domains created by the Sponsor/Applicant
    4. Reviewers will ensure there are no other existing domains to place the variables that are in the SUPPQUAL domain or multiple SUPP--domains
  5. The validation of the SDTM and ADaM will be reconciled by the Sponsor/Applicant to ensure errors are resolved or explained as appropriate in the Validation and Data Interpretation Report.
    1. Sponsor/Applicant should validate their submissions using the OpenCDISC validator (http://www.opencdisc.org/ disclaimer icon )
    2. CBER requests that the Sponsor/Applicant include a validation result, and a Validation and Data Interpretation Report with their regulatory submission.
    3. CDISC team will review the sponsor's validation result, and the Validation and Data Interpretation Report. CBER CDISC team will also validate the regulatory submission for SDTM and ADaM formats and will send a notification with the validation report to the CBER RPM.  If there are any errors, the CBER RPM will contact the Sponsor/Applicant.
    4. CBER encourages Sponsor/Applicant to plan to use the Clinical Data Acquisition Standards Harmonization (CDASH)disclaimer icon standard format to collect their clinical study data as early as the pre-IND stage to avoid legacy datasets being converted into SDTM format in final submission. 
    5. CBER currently accepted versions of Study Data Tabulation and Analysis Standards:
      1. CDISC define.xml Version 1.0 disclaimer icon
      2. CDISC define.xml Version 2.0  disclaimer icon
        • Used for study data definition specification
      3. CDISC SDTM Version 1.3, Implementation Guide 3.1.3 disclaimer icon
        • Used for Human study data tabulation, and clinical study data collection reference
      4. CDISC SDTM Version 1.2 Amendment, Implementation Guide 3.1.2 Amendment 1 disclaimer icon
        • Used for Human study data tabulation, and clinical study data collection reference
      5. CDISC SDTM Version 1.2, Implementation Guide 3.1.2 disclaimer icon
        • Used for Human study data tabulation, and clinical study data collection reference
      6. CDISC SDTM Version 1.1, Implementation Guide 3.1.1 disclaimer icon
        • Used for Human study data tabulation, and clinical study data collection reference
        • Timing – Only for studies initiated prior to 2011-06-13
        • Date Support Ends - 2015-01-28
      7. CDISC ADaM Version 2.1, Implementation Guide 1.0 disclaimer icon
        • Used for Human study data analysis
  6. Prior to regulatory submission the Sponsor/Applicant is requested a Gateway test submission or CBER DCC (CD-ROM)
    1. The test submission may be in conjunction with the eCTD or may be an eCTD skeleton with the SDTM and ADaM formatted data and define.xml file in the module 5 of clinical study report folder (M5 folder).
    2. RPM will Email the STN number to CBER CDISC Team for validation.

 

SUBMISSION

  1. Sponsor/Applicant will document CDISC submission on their Cover Letter
  2. Submission may be received as an eCTD via the Gateway (SDTM and ADaM data formulation will be in the Module 5 of clinical data report) or paper/CD-ROM to CBER's DCC
  3. For each study in the submission all domains will be evaluated for conformance to the SDTM and ADaM standards:
    • SDTM domains for example, AE (Adverse Events), DS (Disposition) or EX(Exposure) will be evaluated by visual conformance
    • ADaM domains for example, ADSL (Analysis Data Subject Level), and ADAE (Analysis Data Adverse Events) will be evaluated by visual conformance
  4. For each of the two datasets, there will be a visual inspection of the first four columns in the following order: STUDYID, DOMAIN, USUBJID, --SEQ (-- is either AE, DS or EX).


SDTM/ADaM DATASET and DEFINE. XML FILE LOCATION in eCTD SUBMISSION

  1. SDTM datasets should be placed in the following hierarchy folders:
    Module 5 of eCTD:
    • Clinical Study Reports
      • Reports of Efficacy and Safety Studies
        • Disease Name (for example, Haemophilia B)
          • Clinical trial studies
            • Specific clinical trial study
              • SDTM`
                • Data Tabulation Data
                  • Data Tabulation Datasets
  2. ADaM datasets should be placed in the following hierarchy folders:
    Module 5 of eCTD:
    • Clinical study reports
      • Reports of Efficacy and Safety Studies
        • Disease Name (for example, Haemophilia B)
          • Clinical trial studies
            • Specific clinical trial study
              • ADaM
                • Data Analysis Data
                  • Data Analysis Datasets

    ADaM domains should be named as "adxx", for examples, adsl, adae, adlb.

  3. A "validation and data interpretation report" should be placed in the following hierarchy folders:
    Module 5 of eCTD:
    • Clinical study reports
      • Reports of Efficacy and Safety Studies
        • Disease Name (for example, Haemophilia B)
          • Clinical trial studies
            • Specific clinical trial study
              • Data Tabulation Data
                • Data Tabulation Data Definition
  4. A define. xml file should be placed in the following hierarchy folders:
    Module 5 of eCTD:
    • Clinical study reports
      • Reports of Efficacy and Safety Studies
        • Disease Name (for example, Haemophilia B)
          • Clinical trial studies
            • Specific clinical trial study
              • Data Tabulation Data
                • Data Tabulation Data Definition

 

VALIDATION

  1. OpenCDISC Validator is the tool that will be used for validation by the Sponsor/Applicant.
  2. The study validation rules are available for download as standard configuration files for OpenCDISC Validator at http://www.opencdisc.org/ disclaimer icon . The OpenCDISC-Validators listed below are acceptable: 
  3. The SDTM and ADaM will be validated together. The Sponsor/Applicant will need to resolve all the errors identified during the validation or justified in the Validation and Data Interpretation Report.
  4. CBER CDISC Team will perform the validation for the regulatory submission.
  5. The define.xml file will be validated using OpenCDISC tool
    • If, the define.xml passes, SDTM datasets will be validated
    • If, the define.xml fails, SDTM cannot be validated until the define file is corrected.
  6. Upon completion of the validation, a notification will be written to document that either the data is acceptable or that the data requires correction.
  7. The notification and the Validation Report will be appended to the regulatory submission.
  8. CBER CDISC Team will send the RPM an email summarizing the results of the validation and any action required.
  9. The RPM will communicate the results of the validation to the Sponsor/Applicant by sending a copy of the Validation Report and scheduling a meeting as required to discuss resolution of issues.

 

REVIEW

  1. Review continues the same as it occurs today