1. FDA Standards Development and Implementation Randy Levin, M.D. Director, Office of Information Management Center for Drug Evaluation and Research Food and Drug Administration Pharm Toxicology Advisory Subcommittee Meeting June 10, 2003

2. Overview Standards organizations –FDA Data Council, CHI, HL7, ICH, CDISC Initiatives –Electronic submissions of applications –Clinical and non clinical study data –Annotated ECG waveform data

3. Standards Development Organizations Government –e.g., FDA Data Council, Consolidated Health Informatics Accredited Standards Development Organizations (SDO) –e.g., Health Level Seven (HL7), American National Standards Institute (ANSI) Other –e.g., ICH, CDISC

4. FDA Data Council –Standards development for health and regulatory data and terminology for the FDA –Representatives from all agency centers and Office of the Commissioner Standards –Involved in national and international standards development efforts

5. Standards Development Process Centers/Offices Identify data or terminology standard need Standard Development Organization Working group of FDA experts Data Council Coordinate development and promote implementation

6. Consolidate Health Informatics CHI –Part of President’s eGov initiative –Set healthcare related standards for interagency use –Representatives from government agencies involved in healthcare (e.g., HHS, DoD, VA) Standards –Use HL7 messaging standards –LOINC for laboratory tests terminology –Others related to primary health care DICOM for transmission of radiology images NCPDP for prescription messages IEEE standard for ECG monitoring messages

7. Health Level Seven Standards Development Organization for issues related to healthcare information –Accredited by the American National Standards Institute (ANSI) –Open, international membership Involved in standards development activities –Health Insurance Portability and Accountability Act –National Health Information Infrastructure –Consolidated Health Informatics Technical committees for development of FDA standards –Regulated Clinical Research Information Management –Vocabulary –Government special interest group

8. ICH International Conference on Harmonisation –Develop standards for communication between regulatory authorities and pharmaceutical industry –Representatives from drug regulatory authorities in the US, EU and Japan and pharmaceutical organizations (i.e., PhRMA, EFPIA and JPMA) Standards –Common Technical Document –Electronic Common Technical Document –Individual case safety reports –MedDRA

9. CDISC Clinical Data Interchange Standard Consortium –Develop standards for communication of clinical trial data between pharmaceutical partners and between pharmaceutical companies and regulatory authorities –Representatives from vendors, pharmaceutical companies, CROs, industry consultants and government agencies Standards –Submissions data model

10. Standard Initiatives Electronic submissions of applications Study reports Structured protocols Structured Product Labeling Individual Case Safety Report Electronic MedWatch Stability data Annotated ECG waveform data Study data

11. Clinical and Animal Study Data Data standards –Organization based on CDISC version 3 submission data model –Terminology Standard procedures –Analysis tools –Repository

12. CDISC Version 3 Submission Data Model A study is a collection of observations Types of observations –Interventions Therapeutic and experimental treatments –Events Incidences independent of planned study evaluations (e.g., adverse reactions) –Findings Observations resulting from planned evaluationsons to address a specific question (e.g. lab test result)

13. Standard Descriptive Variables Observations characterized by descriptive variables Types of descriptive variables –Topic identifies the focus of the observation –Identifiers identifies the subject of the observation –Timing describes the start and end of the observation –Qualifiers describes the traits of the observation

14. Observations Characterized Using Standard Descriptive Variables Subject 101Anauseahad mildstarting on study day 6 Qualifiers Identifier Timing Topic Example Observation

15. Annotated ECG Waveform Data Data standards –Organization based on HL7 RIM version 3 message –Information transported in XML file Standard procedures –Viewer –Analysis tools –Repository