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

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

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.

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.

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

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 : http://www.cdisc.org/standards-and-implementations 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

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)

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.

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 .

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

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

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

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

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”.

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.

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.

THANK YOU! Questions? nlewin@emmes.com www.emmes.com