1. Translational Research and Patient Safety in Europe TRANSFoRm: Requirements analysis for the learning healthcare system.

2. Translational Research and Patient Safety in Europe SAFER CLINICAL PRACTICE MORE RESEARCH EVIDENCE TRANSFoRm -INTEGRATION -INTEROPERABILITY -SERVICES KNOWLEDGE TRANSLATION EPIDEMIOLOGICAL STUDIES AND RCTS The learning healthcare system

3. Translational Research and Patient Safety in Europe Demonstration and dissemination User requirements Development and Evaluation WP7 SYSTEMS AND SERVICES FOR DATA INTEGRATION WP 1 RESEARCH USE CASES WP 2 PATIENT SAFETY USE CASE ICT WP8 DEMONSTRATION INDUSTRY CONTRACT RESEARCH ORG ACADEMIA WP9 DISSEMINATION WEBSITE PUBLICATION WORKSHOPS PROTOTYPES COLLABORATION INFRASTRUCTURE TECHNOLOGY PLATFORMS WP10 MANAGEMENT

4. Translational Research and Patient Safety in Europe Diabetes use case: research questions RQ1: Are well selected single nucleotide polymorphisms (SNPs ) in T2D patients associated with the development of complications as coronary artery disease and retinopathy in a sample of at least 10.000 subjects from the European Union population? RQ2: Are well selected single nucleotide polymorphisms (SNPs) in T2D patients associated with variations in drug response to oral antidiabetics? RQ3: Which genetic markers (SNPs) are associated with T2D related complications as diabetic nephropathy?

5. Translational Research and Patient Safety in Europe GERD: research questions What is the association between the development of esophageal carcinoma and length of GERD history/ PPI use? [Case-control study] What is the effectiveness of on demand v continuous use of PPI in GERD? [RCT]

6. Translational Research and Patient Safety in Europe PPI consumption Age Gender BMI NSAID/ASA Matched controls Identification Reported cancer cases Research database eHR Population registry Cancer registry Identification Tracking -10 yrs Drug registry PPI Option 2: Case control study GERD Case-control study

7. Translational Research and Patient Safety in Europe eCRF0 PHC Web eCRF EVENT DRIVEN eCRF12 eCRF-.5 Wash out PPI test Randomization Verification Q0 Q3 Q6 Q9 Q12 Q-.5 eCR F Data collection GERD RCT

8. Translational Research and Patient Safety in Europe Overall requirements table RequirementNoteUse case AuthorisationExplicit or generalCohort and case-control, RCT ConsentInformed or explicitCohort and case-control, RCT Linked phenotypeMaintained and refreshedCohort and case-control Genetic dataBrowsing and selectionCohort and case-control RecruitmentEmbedded real-time in eHR, manages contact and consent Cohort and RCT eCRFA functional tool rather than an CTDMS Cohort and RCT Research subject portalPatient Related Outcome Measures Cohort and RCT

9. Translational Research and Patient Safety in Europe Modeling Consent Consent for entry into an RCT requires ‘informed consent’ Consent for re-use of data requires ‘explicit consent’ Therefore : – Potentially eligible subjects become research subjects after consent – Two different types of consent are needed

10. Translational Research and Patient Safety in Europe Authorization Control of release of data is encapsulated in a functional zone model in order to clarify the use and access to different types of data Consent and authorization are used to control the flow of data

11. Translational Research and Patient Safety in Europe Rapid phenotyping The system needs to support: – Rich semantic queries of the target data – Assembly of a cohort – Repeat data collection from this cohort by tracking and updates at time intervals specified in the study protocol

12. Translational Research and Patient Safety in Europe Access to genotype Access to SNP data for the selected cohort: – Linkage of phenotype data with SNP data for same patients using pseudonymzation – Browsing and extraction of available SNPs for analysis – Protection mechanisms for vicarious identification

13. Translational Research and Patient Safety in Europe Real time recruitment Crucial to incident case recruitment Embedded within/alongside the eHR Standards-based plug and play Integration with clinical workflow Requires EN/ISO13606 to integrate detailed clinical models and archetypes Business model

14. Translational Research and Patient Safety in Europe Recruitment service For prevalent case recruitment Can be based on asynchronous rather than synchronous services May incorporate a data warehousing solution May involve data linkage

15. Translational Research and Patient Safety in Europe Web questionnaire Database (personal) eHR Data extraction GP Other databases CRF Database (anonymous) Researcher Functional eCRF tool

16. Translational Research and Patient Safety in Europe Patient GP Web questionnaire eCRF Database eHR reminders alarm Data extraction Researcher Other databases Database manager Subject portal for PROM

17. Translational Research and Patient Safety in Europe Current progress Use case development Experimental background to DSS Survey of network capacity and IT resource Model of data comparability Legal and ethical survey Provenance framework Security Framework QA Framework

18. Translational Research and Patient Safety in Europe