RCRIM Off-cycle Meeting

1. RCRIM Off-cycle Meeting Barbara Tardiff, Randy Levin and Ed Tripp, co-chairs

2. Agenda 8:30 Overview of RCRIM work – Randy Levin, Ed Tripp 10:30 BRIDG – Julie Evans, Doug Fridsma 13:30 WHO Clinical Trial Registry – Becky Kush 14:30 Terminology – Bron Kisler, Margaret Haber 15:30 Regulated Product Submission – Jason Rock

3. Overview of RCRIM Work Randy Levin, Ed Tripp

4. HL7 Mission "To provide standards for the exchange, management and integration of data that support clinical patient care and the management, delivery and evaluation of healthcare services. Specifically, to create flexible, cost effective approaches, standards, guidelines, methodologies, and related services for interoperability between healthcare information systems."

5. Health Level Seven • Accredited by the American National Standards Institute (ANSI) • Open, international membership • Technical Committees directly responsible for the content of the Standards; Special Interest Groups explore new areas that may need coverage • Defines messages, document structures, and terminology to support the systems and processes used in the collection, storage, distribution, integration and analysis of research and healthcare information.

6. Governance • Managed by Board of Directors, comprised of eight elected positions and three appointed positions. • Technical Committees and Special Interest Groups are responsible for defining the content of the Standards. Each Technical Committee and Special Interest group is chaired by two or more co-chairs. • Collectively, co-chairs comprise the Technical Steering Committee, which votes on issues related to the standard. Votes of the Technical Steering Committee are passed as recommendations to BOD, who make final decision. • Well-defined set of operating procedures to ensure openness and balance of interest. Meetings and voting cycles are regularly scheduled and open. • Anyone who is interested can participate and contribute at face-to-face meetings and in scheduled teleconferences but only registered voting members can vote during formal ballot cycles.

7. Architectural Review Board Clinical Context Object Workgroup (CCOW) Clinical Decision Support Control/Query Education (admin) Electronic Health Records Electronic Services Financial Mgmt. Implementation (admin) Infrastructure and Messaging Marketing (admin) Medical Records/Information Management Modeling & Methodology Orders/Observations Patient Administration Patient Care Personnel Management Process Improvement (admin) Publishing (admin) Regulated Clinical Research Info Mgmt. Scheduling & Logistics Security Structured Documents Tooling (admin) Vocabulary. Active technical committees

8. Devices Health Care Devices Imaging Integration Laboratory Selected therapeutic areas Cardiology Emergency Care Anesthesia Pediatrics New frontiers Clinical Genomics Patient Safety Public Health and Emergency Response Other: Arden Syntax Attachments Clinical Guidelines Community Based Health Services Conformance Government Projects Java Pharmacy Templates XML Special Interest Groups

9. The Reference Information Model (RIM) • Cornerstone of the HL7 Version 3 development process. An object model created as part of the Version 3 methodology, the RIM is a large pictorial representation of the clinical data (domains) and identifies the life cycle of events that a message or groups of related messages will carry. • Shared model across all domains and is the model from which all domains create their messages. • Explicitly represents connections that exist between the information carried in the fields of HL7 messages, essential to enabling interoperability.

10. RIM

11. Ballot Types • Committee Level Ballot • Membership Ballot • Draft Standard For Trial Use • Informative Ballot

12. The Ballot Schedule

13. RCRIM • Focus is standards that improve or enhance information management during research and regulatory evaluation of the safety and efficacy of therapeutic products or procedures worldwide. • Participation includes FDA and international regulatory agencies, other government agencies (e.g. CDC), PhRMA, CDISC, academic research organizations, biopharmaceutical companies, and vendors and service providers who operate in pharmaceutical market. Regulated Clinical Research Information Management (RCRIM) Technical Committee

14. RCRIM • Defines messages, document structures, and terminology to support the systems and processes used in the collection, storage, distribution, integration and analysis of clinical research and drug development information. • Interchange structure specifications developed to conform to business requirements and data and information needs of regulatory authorities and pharma industry AND common information model, defined data types, controlled vocabularies, and code lists.

15. Standards Development and Adoption Research Process Standardized representation of clinical trial protocol Research Data Periodic reporting of clinical trial laboratory data* Annotation of ECGs* Data for regulatory submission (clinical, non-clinical, pharmacogenomic) Clinical trial registries Regulatory Submissions Structured product labeling* Stability data reporting* Regulated Product Submission Surveillance Individual Case Safety Report* Generic Incident Notification *Approved and recognized as ANSI standard RCRIM

16. Standards Available and in Use Structured Product Label • Specifies structure and semantics for the regulatory requirement and content of product labeling and has been approved as a Clinical Document Architecture (CDA) (based on HL7 RIM) at the membership level and is recognized as an ANSI standard. • FDA Electronic Labeling Rule has been implemented and provides for use of new technologies (e.g. SPL) as available. FDA Physician Labeling Rule requires highlights supported by SPL. • Several vendors have or are developing application that support SPL. FDA has received nearly 1,000 submissions in this format. • Implementation efforts underway to support Physician Labeling Rule (PLR) RCRIM

17. Standards Available and in Use Notifiable Condition Report • For public health/biosurveillance reporting Individual Case Safety Report (ICSR) • Meets requirements of ICH E2B. Electronic replacement for Medwatch RCRIM

18. Available and in Use Annotation of ECGs (Annotated ECG waveform standard) • Fully balloted Version 3 RIM message and recognized as ANSI standard; Implementation Guide approved. • FDA has now received thousands of submissions in this format eStability Data • Drug Stability Report (for submitting product stability data to the FDA) fully balloted as HL7 Version 3 message. RCRIM

19. Standards Available and in Use Periodic Reporting of Clinical Trial Laboratory Data • Based on CDISC LAB Model V1.0; fully balloted Version 3 RIM message and recognized as ANSI standard • Release 2 incorporating PGx data and other extensions in ballot process. RCRIM

20. Standards Under Development Structured Clinical Trial Protocol (SCTP) • Release 1 (subset of elements) balloted as an HL7 Clinical Document Architecture (CDA) at the committee level in May 2004 • Protocol Representation (PR) Group defining standard elements and semantics for the content of clinical trial protocols, with goal of creating a machine-readable electronic protocol representation. • Messages for two related use cases under development. • Clinical trial registries • Project to develop requirements and interchange standards approved September 2004 • eDCI (electronic definition of Data Collection Instrument) • Undertaking to create an HL7 V3 message to convey the definition of an Data Collection Instrument between applications; Being developed under auspices of NCI as early adopter. Potential for use as instructions to EHR system. RCRIM

21. Clinical Trial Registry Message • HL7 message specification for submission of trial information to external clinical trial registries, e.g.ClinicalTrials.gov, EudraCT, PDQ, WHO • Additional Use Cases: • Internal project management tools for trial/protocol tracking • Regulatory submission RCRIM

22. 2010 2007 2006 2005 2008 Draft and Ballot ICH SCTP HL7 Message Protocol Representation Timeline Additional Ballot Cycles Draft General Clinical Trial Registry HL7 Message Ballot General Clinical Trial Registry HL7 Message ANSI Standards Additional Ballot Cycles Draft genCTR Implementation Guide Finalize genCTR Implementation Guide BRIDG Modeling: PR Element Spreadsheet, Trial Design Finalize SCTP Implementation Guide Draft SCTP Implementation Guide Develop Clinical Trial Eligibility Criteria Update CDISC Glossary and Publish Annually in ACT RCRIM

23. Standards Under Development • Generic Incident Notification (GIN) • To support generic reporting for process improvement and organizational learning • Regulated Product Submission • Project to define a message that is general enough to be used broadly for submissions across all regulated products and includes information (metadata) that allows regulators to support structured review RCRIM

24. Regulated Product Submission Scope • Animal and Human products including but not limited to food additives, human therapeutics, veterinary products, and medical devices • Same message structure for all product types • Different controlled lists for each product type • Worldwide use Out of Scope • Submission content Planned for later release • Inclusion of information about the submission (e.g. information currently collected on application forms) • Two-way communications. RCRIM

25. RPS: Phase 1 • Transmission of electronic submissions for a regulated products. • Tagging of submissions for effective review, including, but not limited to allowing creation of a table of contents. • Provides an electronic submission standard to regulated products where no submission standards exist. • Basic requirements: re-use of documents and document components; management of submission lifecycle, submission of form data (different for each regulated product) • Allows applicants to re-use documents that were already submitted. In the case of human therapeutics, standard will allow applicants to move from an IND to a marketing application seamlessly. RCRIM

26. Current Ballots From RCRIM • HL7 Version 3 Standard: Patient Safety: Generic Incident Notification, Release 1 • HL7 Version 3 Standard: Periodic Reporting of Clinical Trial Laboratory Data, Release 2 • HL7 Version 3 Standard: Regulated Product Submission, Release 1 All are Draft Standards for Trial Use (DSTU)

27. Agenda 8:30 Overview of RCRIM work – Randy Levin, Ed Tripp 10:30 BRIDG – Julie Evans, Doug Fridsma 13:30 WHO Clinical Trial Registry – Becky Kush 14:30 Terminology – Bron Kisler, Margaret Haber 15:30 Regulated Product Submission – Jason Rock