New FDA Documents
Discussion of
Implementation Considerations
Monika Kawohl
Principal Statistical Programmer
Accovion GmbH, Marburg, Germany
FDA Submissions - Experiences
Questions
• Who has been involved in preparing SDTM for submission to FDA?
• Who has been involved in preparing ADaM for submission to FDA?
• Who has been involved in preparing CDISC mock submissions?
• Who has experiences with submitting in other/hybrid data formats?
• Who has been involved in discussions with the FDA?
• Experiences with submission of data pools in CDISC formats to support
integrated analyses?
• Who has contacted the FDA with general questions or
Who provided feedback on current FDA documents?

For standardized data submission questions, contact:
EDATA@fda.hhs.gov.

For center specific contacts see:
http://www.fda.gov/ForIndustry/DataStandards/StudyDataStandards/default.htm
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Chance to Get Involved in Discussions with FDA
Support the FDA/PhUSE Collaboration
see http://www.phuse.eu/css
FDA/PhUSE Working Groups
• Data Validation and Quality Assessment
• Standardizing Data within the Inspection Site Selection Process
• Challenges of Integrating and Converting Data across Studies
• Standards Implementation Issues with the CDISC Data Models
• Development of Standard Scripts for Analysis and Programming
• Non-Clinical Road-map and Impacts on Implementation
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CDER Common Data Standards Issues Document
Version 1.1 (Dec-2011) Updates regarding SDTM
• Implementation of Amendment 1 to SDTM 1.2 strongly preferred
• Subject Elements (SE) mandatory SDTM domain
• EPOCH in every subject-level domain

ELEMENT/ETCD desired but not requested
• SUPPAE.AETRTEM
• Splitting domains (> 1GB)

provide split domains in separate subdirectory SPLIT???
• File size considerations

use required maximum length of variable
instead of 200 for every character variable
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CDER Common Data Standards Issues Document
FDA “Expected“ SDTM Variables
• Baseline flags (--BLFL) in findings domains
• Study day (-DY) for every -DTC

derived based on RFSTDTC

RFSTDTC = start of treatment in most study designs
• Death diagnosis or comments in pathology reports
SUBJID = Subject identifier used in Study Report
define.xml + define.pdf (printable version, no need for hyperlinks)
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CDER Common Data Standards Issues Document
Version 1.1 Updates regarding ADaM
• Analysis Datasets should include

appropriate numeric time variables
(e.g. with value 8 for “Week 8“)

basic demographic variables (e.g. sex)

all covariates named in the protocol
• Analysis datasets should be derivable from SDTM

To support traceability from results to collected data

Not new but important!
General Recommendation: Contact the FDA
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CDISC/FDA Webinar
CDISC Standards In the Regulatory Submission Process,
presented 26 January 2012
• recorded webinar
• presentation slides
• available at http://www.cdisc.org/webinars
• Follow-up on topics of special interest

FAQ Database from CDER Data Standards Questions Team
-

Accessible by the public?
Importance of Reviewer‘s Guide for adequate documentation
-
Standard template?
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FDA Standardized Study Data Draft Guidance
http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/
Guidances/UCM292334.pdf (Feb-2012)
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FDA Study Data Standards Resources
http://www.fda.gov/ForIndustry/DataStandards/StudyDataStandards/default.htm
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Implementing SDTM Amendment 1, FDA Docs.
Information for new DM variables
• Store data in DM only vs. DM + another Domain?

Date/Time of Informed Consent

Date/Time of Death

Date/Time of End of Participation
Derive AE Treatment Emergent Flag in SDTM (SUPPAE)?
When to use SUPPQUAL?
Generally provide SDTM variables “Expected“ by FDA?
Process to ensure appropriate variable length
Process for splitting domains and how to document it
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Implementing SDTM Amendment 1, FDA Docs.
How to create the define.pdf?
Always create a Reviewer‘s Guide?
• Per submission datasets folder
(i.e., separate ones per set of SDTM or ADaM data)?
• Describing SDTM/ADaM and/or multiple studies together
• Contents?
OpenCDISC SDTM (/ADaM) validation
• Timing of compliance checks within the process?
• Describing/addressing issues
Define.xml schema validation/OpenCDISC define.xml validation
How to describe which SDTM versions and appendices are used?
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Implementing Controlled Terminology (Updates)
Excerpt from Draft Guidance: Providing Regulatory Submissions in Electronic Format - Standardized Study Data
(Feb-2012)
“When planning a study (including the design of case report forms, data management systems, and
statistical analysis plans), the sponsor should identify which FDA-supported standard terminologies to
use for submission.
If a sponsor identifies a concept for which no standard term exists, we recommend that the sponsor
submit the concept to the appropriate terminology maintenance organization as early as possible to
have a new term added to the standard dictionary. We consider this good terminology management
practice for any organization. The creation of custom terms for a submission is discouraged (i.e., so
called extensible code lists)...“
Use of CDISC New Term Request Webpage?
• Experiences/Response Times?
How to deal with CDISC CT Updates within a project?
Documentation of CT version(s) used
• How to distinguish between CDISC CT values and sponsor
extensions?
Experiences with Updated Trial Summary (TS) domain?
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Trial Summary (TS) Update
Alignment with ClinicalTrials.gov
• New Trial Summary Parameters
Indication of Use per Trial Summary Parameter
 Required
 Conditionally
Required
 Expected
Introduction of NULL FLAVOR Variable
• Coded Reason if TSVAL=missing
Introduction of underlying CT information variables
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Trial Summary (TS) Update Sample
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