1. The Correct e- Mixtures (A fully validated EHR, the way forward) Brendan Delaney Guy’s and St Thomas’ Charity Chair in Primary Care Research

2. Requirements of observational research Data description Cohort management Data quality Data linkage –Semantic interoperability –Privacy –Matching

3. Requirements of interventional research Feasibility –Simple via distributed search –Complex via CPRD Recruitment –Privacy requirements Data management –eSource Adverse Event Reporting

4. What tools exist currently Legacy systems –Electronic Health Record Systems –Web based data collection forms and CTDMS –Clinical trial administration systems Projects in pilot and deployment CPRD Observational research platform Wellcome Trust eLung and RetroPro ePCRN FP7 TRANSFoRm

5. OBSERVATIONAL RESEARCH PLATFORM AND INCIDENT CASE RECRUITMENT

6. CPRD A Primary care clinical data warehouse Vision EHR (~20%) 600 clinics out 2500 clinics in the UK (out of 10300 clinics) provides a good sample UK primary care data Expanding to other three UK eHR vendors –50-60% coverage of UK pop –More streamlined and daily updates –Linkage

7. eLUNG and RETROPRO eLUNG: antibiotics vs standard care for COPD exacerbation RETROPRO: comparative study of different types of statins Recruitment at point of care (LEPIS) Feasibility studies funded by HTA and Wellcome Trust

8. The Approach Local autonomous agents to identify potential participants and facilitate their recruitment Interactive agents: with the physician Non-intrusive to the physician healthcare process Can easily be dismissed but yet has memory of GP actions Standardised and vocabulary controlled Scalable and highly configurable

9. Agent-based Technology Autonomous provides configurable flexibility adaptive to user requirements non-intrusive behaviour Asynchronous automation agents self-update their knowledge/registry configure for performance needs

10. Overall Architecture GPRD warehouse CTMS CCS LEPIS SiS Workbench Clinical trial data management system LEPIS: Local Eligible Participant Identification Service CCS: Central Control Service

11. FEASIBILITY AND RECRUITMENT OF PREVALENT CASES

12.  Funded 2004-7 by National Institutes of Health ‘Roadmap’ Program – pilot.  Facilitates recruitment by establishing a secure distributed query process for eHRs to identify eligible subjects  Proof of concept interoperable clinical trial data management system for Primary Care  NIHR NSPCR, Wellcome Trust (CPRD, ALSPAC), HTA, EU FP7 The electronic Primary Care Research Network (ePCRN)

13. Confidentiality and data security  Confidentiality - for subjects not having consented to use of their data for research  Search reports only ‘counts’ - NO DATA is extracted  Subjects are flagged locally  Security  OGSA-DAI & GTK4(certificates and authorisation)

14. Define eligibility criteria

15. Define the clinical problem semantically

16. Define further clinical problems, drugs or vital signs

17. Count eligible community subjects

18. Research network director approval tool

19. ADVANCED OBSERVATIONAL PLATFORM AND EMBEDDED ELECTRONIC CASE REPORT FORMS

20. Existing methods of trial data management are limited  No standardization of electronic case report forms (CRFs), timelines etc.  No reusability of data elements  No standardization of data structures  No automatic linkage of data elements and data structures

21. TRANSFoRm Consortium

22. Aims of TRANSFoRm To develop methods, models, services, validated architectures and demonstrations to support: –Epidemiological research using GP records, including genotype-phenotype studies and other record linkages –Research workflow embedded in the EHR –Decision support for diagnosis 22

23. Type 2 DM study Question: Relationship between SNPs and response to oral T2DM medication Genotype-Phenotype record linkage study –Privacy model –Record linkage (browsing, selecting, extracting) –Data quality tool –Provenance tool 23

24. GORD Treatment study Question: Effectiveness of on-demand v continuous PPI RCT with event-initiated patient-related outcome measures –Trigger within EHR –Semantic Mediator –eCRF tool (embedded in EHR) 24

25. Overall Architecture Distributed Nodes Middleware (Distributed Infrastructure) End User Tools and Services Support Services

26. Data source or collection Care Zone Non-care Zone Primary data Secondary data in DB Data use Research Zone Compatible use incompatibl e use Identifyng data Private data Identifiable data Genetic data Medical data Non- identifiable Data controller: Different national definitions for personal data, sensitive data, controller / processor, re-use of data for scientific purpose research

27. eSource two models

28. Discussion Ongoing mainly EU-funded projects will provide a stream of innovations in: –Computable representations of study designs –Interoperability –Data quality –Privacy, security and provenance –Workflow

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