1. Data Management in Clinical Trials

2. E-CRF design / P-CRF Data entryData validation Data import Clinical coding DATABASE CLOSURE Database Closure Documents Database lock Tables & listings / graphs SAS programming finalising analysis database Draft report Final report Database export Protocol Monitoring Data Management Plan

3. Data Management Plan, DMP The DMP is a description of data management activities for capturing and validating data during a study.

4. Included in DMP 1.List of abbreviations 2.Definitions/Clarifications 3.Introduction 4.Study information/Description 5.Data Management System (CDMS) 6.Data management procedures 7.Data entry procedures 8.Data query handling 9.Data validation procedures 10.Coding procedures 11.Database closure 12.Export of data 13.Import of data 14.Appendix

5. CRF CDISC/CDASH standard or sponsors standard (should be stated in the contract). Footnote on all pages containing: version, date and initials Header on all pages containing: study number, site number, subject number, subject initials/ID, visit number. Follow ICH GCP guidelines. Follow GCDMP guidelines.

6. P-CRF (paper CRF) P-CRF Reviewed by internal study team (PM, DM, STAT, monitor) before sent to sponsor Reviewed by clinical team (sponsor, investigator, study nurse) Approved by sponsor (if required by sponsor), PM, DM and STAT (date and signature) Remember CRF Receipt Log when using P-CRF

7. E-CRF (Electronic CRF) E-CRF Created in CDMS Reviewed by internal study team (PM, DM, STAT, monitor) Reviewed by clinical team (sponsor, investigator, study nurse), review = access to a test database Approved by sponsor (if required by sponsor), PM, DM and STAT (date and signature)

8. DATA ENTRY (DE) At site (E-CRF) Internal (P-CRF) Single or Double DE Data Entry Log Data Entry Problem Sheet (DEPS) Data Handling Instructions E.g. Enter date as YYYY-MM-DD E.g. Enter Not Applicable as NA

9. QUERY HANDLING P-CRF Data entry errors documented in DEPS (Data Entry Problem Sheet). DM investigates whether these errors should be queries/DCF. CDM can also produce queries from logical checks. During QC.

10. QUERY HANDLING E-CRF Query handling in the system according to the E-CRF Queries can be generated by monitor or DM within (or outside) the system. Logical checks can be included in the CDMS or be created outside the system.

11. QUERY HANDLING All CDM queries are logged (study number, site, subject number, date sent, name of query creator, date received, date when changed in DB in paper CRF, name of person who changed query in DB)

12. CLINICAL CODING Clinical Coding – the translation of medical terminology into a standardized coded format that is recognized nationally and internationally.

13. CLINICAL CODING Study specific coding information in the DMP, e.g. what to code, dictionaries, when coding is to be done. Coding done by assigned coder. Reviewed and confirmed by medical reviewer. Final coding approved (signed and dated) by sponsor. Final coding dictionaries version should be documentet If all been coded or something is uncoded medication/AE/Med hist documented in the DHR (Data Handling Report)

14. DATA IMPORT/EXPORT According to specification in DMP E.g. ECG, biomarkers Validation of imported/exported data Transfer specification

15. DATABASE CLOSURE When all queries are solved: Quality Control Proof Reading (only P-CRF) Logical Checks Approved Clinical Coding Approved Statistical Analysis Plan (SAP) All issues are documented Approved and signed Database Closure Document