1. Study Data Standardization Plan Kick0ff Meeting 23 July 2014

2. Agenda Introductions PhUSE Team Best Practice Guideline Overall objective – development of template for Study Data Standardization Plan Relationship to Study Data Reviewers Guide? Development of work plan – Can we break down the work elements? Next Actions/Plan for follow-up meetings

3. Team Members NameOrganization Bezek, CathyAstellas Pharma Blauwet, Mary BethAstellas Pharma Brennan, MichaelJanssen Chang, TonyAmgen Dwyer, KateFDA Fenaughty, Christine CPfizer Hientzsch, BeateAccovion GmbH Johnson, JamesSummit Analytical Kaufman, LauraPDS, Inc. Kelly, KristinAccenture Kenny, SusanMaximum Likelihood, Inc. Lozano, JaneLilly Naro, NickPfizer Russotto, AnneCelgene Ryley, PamTakeda Simonsson, LindaI-MInd

4. STUDY DATA TECHNICAL CONFORMANCE GUIDE (February 2014) For clinical and nonclinical studies, sponsors should include a plan (e.g., in the IND) describing the submission of standardized study data to FDA. The Study Data Standardization Plan (Standardization Plan) assists FDA in identifying potential data standardization issues early in the development program. Sponsors may also initiate discussions at the pre-IND stage. For INDs, the Standardization Plan should be located in the general investigational plan. The Standardization Plan should include, but is not limited to the following: 1. List of the planned studies 2. Type of studies (e.g., phase I, II or III) 3. Study designs (e.g., parallel, cross-over, open-label extension) 4. Planned data standards, formats, and terminologies and their versions 5. List of and justification for studies that may not conform to the standards

5. STUDY DATA TECHNICAL CONFORMANCE GUIDE (February 2014 ) The Standardization Plan should be updated in subsequent communications with FDA as the development program expands and additional studies are planned. The cover letter accompanying a study data submission should describe the extent to which the Standardization Plan was executed.

6. Additional Topics – Plan for managing pooled analyses – Plan for conversion of legacy study datasets – Relevant controlled terminologies (e.g., MedDRA) and version – by study – Any need for a controlled terminology not addressed by current standards – Targeted questions for FDA – Running summary of discussions and resolutions, meeting minutes

7. Study Data Reviewer’s Guide(SDRG) “The SDRG is intended to describe SDTM data submitted for an individual study in Module 5 clinical section of eCTD.” “The SDRG purposefully duplicates information found in other submission documentation (e.g., protocol, clinical study report, define.xml) in order to provide FDA Reviewers with a single point of orientation.”

8. Study Data Reviewer’s Guide(SDRG) Introduction provides an overview and inventory of standards used on the study. Protocol Description provides a brief orientation to the study and, if necessary, additional context for trial design datasets. Subject Data Descriptions section provides additional context for subject-level SDTM domains that are not adequately documented in define.xml or the SDTM implementation guide The Subject Data Descriptions also describes sponsor-specific annotated CRF conventions as needed Data Conformance Summary documents the validation inputs used to evaluate SDTM conformance and summarizes conformance findings.

9. Example: SDRG Descriptions of Standards and Controlled Terminology Version SDTMSDTM v1.2/SDTM IG v3.1.2 including Amendment 1. Oncology Domains, TU, TR, and RS, have been submitted according to the version released for public comment dated 30-Jan-2011 Controlled TerminologyCDISC Controlled Terminology dated 22- Jul-2011 has been used for all domains except for LB. LBTESTCD and LBTEST use terminology from the 29-Jun-2012 CDISC Controlled Terminology package. Data Definitionsdefine.xml v1.0 Medications DictionaryProprietary sponsor medication dictionary Medical Events DictionaryMedDRA v14.1

10. Proposed Sub-Teams List of studies – Non-clinical – Clinical Plan for managing pooled analyses Relevant controlled terminologies (e.g., Medra) and version – by study Any need for a controlled terminology not addressed by current standards Targeted questions for FDA Running summary of discussions and resolutions, meeting minutes Completion Guidelines? Samples

11. Some Points to Consider When should the Study Data Standardization Plan be drafted (review/approval) Who should coordinate and manage the Study Data Standardization Plan When should the Study Data Standardization Plan be submitted What triggers an updated submission of the Study Data Standardization Plan? How does the Study Data Standardization Plan relate to the drafting/approval of Study Data Reviewers Guide?

12. List of the planned studies Can this list be created/updated once and anticipate use in other contexts – List of studies in IB/Annual Reports – List of studies in NDA/BLA Word Template versus structured content?

13. Next Steps Draft Project Description – Review by PhUSE Steering Committee – Post to Wiki Meeting Frequency? – Propose once a month – Checking (call/email) every two weeks with sub-teams Communication within team? Target deadline? – Sub-team commitement – Project Plan – next month

14. Backup

15. eCTD Module 5 Table of Studies

16. Sample Non-Clinical Table Formats (IB)