Project Sponsors & Participants Bayer Boehringer Ingelheim Bristol Myers Squib Cerner Corporation ClinPhone Inc. Eli Lilly and Company FDA Glaxo SmithKline Hoffman La Roche Lundbeck Millennium NIH: NCI Northrop Grumman Novartis Nycomed Orion Pfizer Procter & Gamble Sponsors: EDC/eSource Taskforce Gold level partners: Procter & Gamble Pharmaceuticals Pfizer Eli Lilly & Company In Cooperation With: HL7 Technical Committee EuroRec Q-Rec

EHR / CR Profile Initiative Commitment to Industry Standards Presentation to RCRIM Atlanta, GA 17 September 2007 Catherine Célingant On Behalf of the EHR/CR FP Working Group Copyright EHR/CR Project

EHR-CR Profile Initiative Project Overview Objective & Strategy Develop a Clinical Research profile to incorporate into the EHR certification programs (US-CCHIT & EU-QRec) to facilitate the inclusion of EHR data in regulatory submissions FDA CDER Division of Scientific Investigations to PhRMA EDC/eSource Taskforce Interest in eSource but no certification in place for EHR systems Invitations by HL7 TC (Lenel James) and Q-Rec (Georges DeMoor) to participate in an EHR certification activity to address Clinical Research needs 11/30/2018 Copyright EHR/CR Project

EHR-CR Profile Initiative Project Overview (continued) Scope Identify critical capabilities (requirements and functions) to conduct clinical research utilizing EHR systems based on: HL7 EHR-S FM Q-Rec EHR FM + Clinical Research-specific requirements Reference and endorse industry standards (e.g., HL7, CDISC, CDASH) Submit to HL7 for formal ballot (~1Q08) Submit to CCHIT & Q-Rec for Certification Approval 11/30/2018 Copyright EHR/CR Project

EHR-CR Profile Initiative Project Overview (continued) Desired Outcomes Healthcare providers Facilitate their participation in clinical research by decreasing data collection burden Regulators Assurance that submission data are generated from reliable sources Sponsors Certification will provide the basis for evaluating EHR systems as source data systems EHR Vendors Provided with encouragement & requirements for incorporating clinical research functionalities into their systems 11/30/2018 Copyright EHR/CR Project

(Minimum Requirement) Emerging and Future EHR-Research Connectivity and Complexity Interoperable Core Connected Integrated Site eSource Site eSource Research System Core Tier 3 Tier 1 Core (Minimum Requirement) EHR systems holding some source data used in Clinical Research meet essential regulatory requirements Electronic data can be electronically extracted such that it can be transferred and loaded into a research system Research systems must still collect trial-specific data Tier 2 Interoperable (Future Ideal) EHR and Research systems work seamlessly together and sit on same international network. Data access & mining capabilities across healthcare & research. EHR holds the complete patient medical record including all clinical trial / research data Connected (Emerging Future) All patient trial data collected via EHR structured data elements and transferred from EHR via automatic/electronic industry standards No further duplication of EHR data Trial-specific data and queries handled via Research system Integrated (Future Vision) Relevant data from EHR and Research System components are seamlessly transferred in both directions with no need for data transcription, EHR System can capture healthcare and trial-specific data Trial data not collected at site is transferred to EHR, Research holds virtually no ‘source’ data.

Clinical Research Needs and Standards Evolution From Paper Based Clinical Research to Electronic From Non-Normalized to Normalized Data From Formatted Data Files to XML Progression to a Future Interoperable State 11/30/2018 Copyright EHR/CR Project

Clinical Research Needs and Standards HL7 Functional Model – Consistency across EHR vendor applications CDISC (CDASH) – Clinical Data Content Standards CDISC (SDTM) – Clinical Data Submission Standards geared towards facilitating analysis HL7 Clinical Statement (basis for HL7 EHR) - Encounter data CDISC-HL7 exchange standard - Data exchange between EHR and sponsor systems Exchange must be bi-directional 11/30/2018 Copyright EHR/CR Project

Copyright EHR/CR Project Back-up Slides 11/30/2018 Copyright EHR/CR Project

Working Group Membership EHR/CR-FP Functional Profile Working Group (International Group) Formed in November 2006 Global representation (Bio-pharmaceutical, EHR Vendor, Clinical Research Vendor, FDA, NIH, EuroRec Q-Rec, CDISC, PhRMA, EFPIA) EHR/CR-FP Co-chairs John D. Mestler Procter & Gamble Pharmaceuticals, PhRMA EDC/eSource Taskforce, eClinical Forum Suzanne Bishop SKB Consulting, eClinical Forum US Richard Perkins ConSept Consulting, eClinical Forum EU Catherine Célingant Millennium Pharmaceuticals, Inc., PhRMA EDC/eSource Taskforce, eClinical Forum 11/30/2018 Copyright EHR/CR Project

Working Group Membership (continued) Marie MacDonald Astellas US LLC Gary Drucker Bayer Healthcare, Pharmaceuticals Tricia Gregory Boehringer Ingelheim Pharmaceuticals Darlene Kalinowski Bristol Myers Squibb Jane Griffin Cerner Corporation (EHR vendor) David Stein ClinPhone Inc (Clinical technology vendor) Linda King Eli Lilly & Company Ian Hamilton Eli Lilly & Company Jay Levine FDA Armando Oliva FDA Joe Salewski FDA Susan Howard Glaxo SmithKline Pharmaceuticals Frank Jensen Lundbeck Pharmaceuticals, EFPIA John Speakman NIH / Cancer Research Foundation Harry Greenspun Northrop Grumman Health Solutions Mitra Rocca Novartis Pharmaceuticals Mathias Poensgen Nycomed GmbH Tina Hartikainen Orion Pharmaceuticals Daijin Kim Pfizer Pharmaceuticals Miguel Valenzuela Roche Products Limited 11/30/2018 Copyright EHR/CR Project

Tier 2 – Integrated (Future Vision) Automatic bi-directional electronic exchange of all clinical research data; single point of data entry at investigator site Electronic Health Record (EHR) System Sponsor Clinical Research System Possibility of use for Virtual Phase IV trials Data and Queries RDM Toolkit Other data Coding Coding Labs Entry of Patient’s Clinical Data EHR: All CDASH data domains Trial-specific data Single point of data entry Data held by Research Systems: Labs CDASH & efficacy populated from EHR system Other EHR system able to collect all patient data as requested by sponsor Physician/Investigator EHR is repository for all patient data, including clinical trial / research data August 2007