1. Quality Control of SDTM Domain Mappings from Electronic Case Report Forms Noga Meiry Lewin, MS Senior SAS Programmer The Emmes Corporation
Target: 38th Annual Meeting of the Society for Clinical Trials (SCT) - Information Systems and Technology in Trials Session

2. Outline General approach of CDISC initiative in Emmes
Motivation and objective of the QC program
Example of SDTM mapping
Program description
Output example
Conclusion

3. Goals of CDISC Integration
Develop in-house SDTM mapping
Incorporate CDISC into every aspect of protocol design, operations, and analyses
Since data managers know the protocol best , it is important to give them the right tools to produce great SDTM domains themselves
Standardize for future scalability
Facilitate transfer of data to other organizations and for FDA submission
This is planned with the vision of standardizing the process for the future, and it will facilitate transfer of data to FDA and other organizations.

4. SDTM – Study Data Tabulation Model
Standard for submission of clinical data domains to FDA
Provides a standard for streamlining the process
Domain are grouped by topics. Examples:
AE – Adverse Events,
DM – Demographics,
CO – Comments,
VS – Vital Signs,
EG – EKG Results
These SDTM domains are submitted with the analysis datasets (ADaM).
The SDTM provides a standard for organizing and formatting data, it streamlines processes of collection, management analysis and reporting.
It is a required standard for submission to the FDA.

5. Motivation
After Qcing many domains I felt that this task was hard and time consuming.
Can be automated by a program.
Goal - improve efficiency – achieved in two ways:
Program:
Run by a non-programmer
Customized by a non-programmer
Output:
Reliable
Easily navigated
After Qcing multiple domains, which was labor intensive, I saw that the process can be programmed and streamlined

6. The program runs after the SDTM domain creation:
Protocol
Study Design
Planning
CDASH
LAB
Data Collection
SEND*
Data Tabulation
SDTM
Statistical Analysis
ADaM
Foundation Standards :
CDISC – Clinical Data Interchange Standard Consortium
SEND – standard for exchange of nonclinical data
CDASH - Clinical Data Acquisition Standards Harmonization
LAB –Laboratory Data Model
ADaM – Analysis data Model

7. SDTM Mapping Process: AE domain example
AE2 form
AE1 form
Multiple CRF forms feed into parent domain and supplemental domain
QC of SDTM annotation
The user adds SDTM annotation of variables through a form builder interface
AE1 normalized format
AE2 normalized format
SUPPAE domain
AE domain
SDTM mapping through a mapping interface - for each SDTM variable enter code to construct it from variables on the forms
Pinnacle 21 (version 2.1.0) is a standard tool. All the other steps are Emmes’ tools.
Multiple forms feed into the same domain because of collection considerations. For example, it is easy to collect unsolicited Aes than solicited Aes.
QC of SDTM mapping: execute queries, view results (replaced by the program)
Platform testing: follow variables from CRFs to domains, refer to rules in SDTM-implementation guide
Pinnacle 21 Validator
(open source tool)

8. 50% savings in time over the manual process.
Automatic QC Process
50% savings in time over the manual process.
Two easy steps, for the WHOLE PROTOCOL:
1. Enter parameters on top of the program.
2. Run.
Submit and rerun if tests failed, after modification.
For each pair of domain and form, the program creates a document with QC results in one run.
All documents are stored in one protocol directory.
For 2 and 3:
The program will create a full set of documents for the protocol.

9. Relationships from SDTM mappings:
PROGRAM INPUT :
User Input :
Relationships from SDTM mappings:
Relationships between domains and forms:
e.g:
Forms feeding into domain AE:
AE1
AE2
Forms feeding into domain CM:
CM1 form
CM2 form
ENROLL form
(from mapping tool)
Protocol name,
gold standard* protocol and project,
location of reports
Relationships between variables on the forms to SDTM variables (from mapping tool)
Rules for correct mapping:
Emmes has a library of SDTM-ready CRFs that can be imported and used on individual studies. This is part of the gold standard concept.
For example : all SDTM variables for the domain should appear in the domain;
Required variables should not be missing
Domains and forms
* A protocol that is completely mapped, verified without errors , that serves as a standard for comparison .

10. PROGRAM OUTPUT:
A set of PDF files for each form-domain pair, for each protocol
Result for each pair of domain and its mapped form
Directory contents for each protocol:
Domain results, independent of form

11. QC report: Domain-Form pair results
First page (snippet): Table of contents of results with page numbers, for hard copy review:

12. QC report: Domain-Form pair results
Second page - Summary of failed tests with links to detailed results:
Title on each page is detailed with all the information for the QC
Each cell links to detailed result
Link to
top on each page

13. QC report: Domain-Form pair results
Second page – List of results for a domain-form pair (snippet)
Results, including the ones that passed.

14. QC Result report – detailed result of each error – SNIPPET (next pages)
In the supp example, the mapping will end up in the domain, without looking it up in the normalized supp format.
When the mapping is”derived” it should have been “CRF”.

15. Program Features and Improvements over the Manual Process
Runs mainly on the mapping to facilitate QC mid process. (Pinnacle21 runs at the end of the process).
Program is transferrable across protocols
Takes advantage of project’s metadata and structure to save user’s data entry time and reduce errors.
Creates reports for all mapped domains and forms in one run.
The reports are user friendly - Summary of failed tests in red (or complete success) is at the top of the report with links to details. User can easily access different levels of details.
Replaces visual observation of the data which is tedious, error-prone and not replicable.
Time saving of tedious task - User can focus on higher level work that can not be programmed
If the rules of the mapping change, the programmer will change the QC program, thus changing it in ONE PLACE and not worry about dissemination of information, different versions etc.
The results of the QC are recorded permanently in the output and this improves keeping track of records, data and dates.

16. Acknowledgements: Sheena Aris, PhD Miebi Stuekerjuergen Angela Soriano
Gaurav Sharma, PhD
Jill Barrett, MPH
Heather Hill, MS
Marian Ewell, ScD
Noble Shore
Abigail G. Matthews, PhD
Special thanks to Sheena Aris from the CDISC initiative team and to my supervisor Abby Matthew for their help with preparing the presentation.
The program is a collaboration with the CDISC initiative team at Emmes.

17. THANK YOU!
Questions?