Donna W. Dorozinsky, RN, MSN, CCRC

1. care Overview of Good Clinical Practice community Donna W. Dorozinsky, RN, MSN, CCRC research teach

2. Welcome • Please silence cell phones • Please limit exits and entrances

3. care Essential Study Documents community research teach

4. Study Documentation

5. Essential Study Documents • Essential Documents are those documents that individually and collectively permit evaluation of the conduct of a trial and the quality of the data produced. ICH GCP E6 guidance 1997

6. Essential Study Documents • Purpose: • demonstrate the compliance of the investigator, sponsor, and monitor with GCP and applicable regulatory requirements. • Assist in the successful management of a trial by the investigator, monitor, and sponsor

7. Essential Study Documents • Grouped into 3 sections • Before the clinical phase of the trial begins • During the clinical conduct of the trial • After completion or termination of the trial

8. Essential Study Documents • Both Sponsor and investigator should establish a study file at the beginning of the trial • At close-out of trial • Confirm that all necessary documents are in the appropriate files • Documents may be subject to an audit • Acceptable to combine some of the documents

9. Before The Clinical Phase Of The Trial

10. Before The Clinical Phase Of The Trial

11. Before The Clinical Phase Of The Trial

12. Before The Clinical Phase Of The Trial

13. Before The Clinical Phase Of The Trial

14. Before The Clinical Phase Of The Trial

15. During the Trial

16. During the Trial

17. During the Trial

18. During the Trial

19. During the Trial

20. During the Trial

21. After Completion or Termination of the Trial

22. After Completion or Termination of the Trial

23. Regulatory Binders • CV and current medical licensesw for the PI, all sub-I, and any others listed on Form FDA 1572 • A completed, signed and dated copy of Form FDA 1572, plus completed and signed copies of any amended Form FDA 1572 • Asigned, dated copy of the official study protocol, plus signed dated copies of any subsequent amendments • IRB approval letter for protocol and consent and any approved advertisement for subject recruitment. • IRB membership roster • Investigator’s Brochure • Lab CAP and CLIA certifications. CV and license for lab director, reference ranges for lab tests • Drug inventory

24. Regulatory Binders • Correspondence to or from sponsor, PI, IRB, Investigational Drug, Pharmacy and subjects • Screening log • Patient log • Monitoring reports • Signature log and delegation sheets • SAE reports and supporting documents • IRB notification of IND safety reports • All correspondence should be stamped with date of receipt Drexel University College of Medicine, Guidelines for the conduct of Clinical Trials, Regulatory Documents 4/27/2004.

25. Source Documentation

26. Source Documentation • Importance of Documentation • Necessary for the reconstruction, evaluation, and validation of clinical findings, observations, and other activities during a clinical trial –ICH 1.52 • Substantiates the integrity of trial data, confirm observations that are recorded and confirm the existence of subjects.

27. Source Documentation • Purpose: • To record a subject’s history, diagnosis, and medical management • Enable monitors to verify that trial data are accurate, complete, and verifiable • Permit a reconstruction of the trial

28. Examples of Source Documents • Past Medical History • Patient medication record • Admission assessment • Nursing records • Vital signs • Lab report that physician initials and dates • ECG • Consultant reports

29. What is not considered source data? • Lab print-out • X-ray report • Others?

30. The Electronic Medical Record • 21 CFR, Part 11 • Applies to records in electronic form that are created, modified, maintained, archived, or retrieved for FDA regulated purposes. • Validation • Limited access • Secure, computer-generated time stamped audit trails.

31. The Electronic Medical Record • Treated same as paper with regards to documentation. • Available to the FDA for audit. • Password and username security.

32. Source Documentation • Apply ALCOA to achieve data quality • Attributable • Legible • Contemporaneous • Original • Accurate

33. Source Documentation • Source documents should be the original document. If a copy is used as a source document, it should be certified that it was verified to be an exact copy of the original, having all of the same attributes and information as the original. • If the original document is retained elsewhere in the study file, the copy does not need to be certified.

34. Source Documentation • Must have: • Subject number or identifier • Date/time of collected data point • Data • Signature of person making observation • Unless data is automated (e.g. Dinamapp printout)

35. Recording of Source Data • Must be permanent • Black ink or typed • Protected from unauthorized change • Nothing that can be erased • Sequence should be chronological • If additions need to be made, they need to be signed and dated. • Original entry must be visible if corrections are done. (audit trail)

36. Recording of Source Data • Corrections should be made according to GCP • Draw a single line through data to be corrected, record new data, initial and date correction. • If reason for change is not obvious, it should be explained. • If data are transcribed (e.g. lab data), the source data is the original laboratory report.

37. Recording of Source Data • Source documents should not be removed from the investigator’s site. • Source documents should never be destroyed. • The first place the data is recorded is the source document.

38. Recording of Source Data • CRF as source document • Data may be recorded directly onto a CRF with no prior written or electronic record. • Any data that is to be recorded directly onto a CRF should be identified in the protocol as per ICH GCP.

39. Recording of Source Data • When a subject drops out of a study • Document the reason for dropping out • Keep a record of attempted and actual patient contacts • Obtain all follow-up information where possible • If unable to obtain follow-up, document the subject as lost to follow-up.

40. Source Documentation Do’s and Don’ts • Do’s: • Do print legibly. • Do use a black ballpoint pen. • Do make sure your letters and numbers are legible and easy to read. • Do complete all sections of each page as requested. • Always use a 24 hour clock. • Dates should be recorded in the day, month, year format (dd/mmm/yyyy).

41. Source Documentation Do’s and Don’ts • Do’s • Checkboxes should be marked with a checkmark or an X • Do use only accepted medical abbreviations.

42. Source Documentation Do’s and Don’ts • Don'ts • Don’t add information at a later date without indicating that you did so. • Don’t date the entry so that it appears to have been written at an earlier time. • Don’t add inaccurate information. • Don’t destroy original documents even if they require error correction. • Don’t alter information. • Don’t double document paper and electronic.

43. Source Documentation Do’s and Don’ts • Don’ts • Don’t leave empty lines or spaces. • Draw a line through the empty line or space to prevent charting by someone else. • Don’t write in the margins • If you need to record additional information, use a progress notes page or use a comments space. • Don’t predate or postdate information.

44. Case Report Forms

45. Where can data be found? • It continues with the Case Report Form or data collection form • CRFs provide the means to collect S/E data required by the protocol which is then transferred to a data base to ensure quality and integrity of the trial • Why are there so many CRFs? • The shoe box and the IRS audit phenomenon • Attestation to credibility, veracity, compliance, etc. • Organization of forms • Amount of data to be collected • Grouping of forms by visit

46. Special Considerations: The eCRF • The computerized eCRF replaces the paper CRF. • Sponsor provided computers used only for eCRF entry. • Computers should be secured within the office. • Password and username security is critical.

47. Investigator-InitiatedClinical Research • In collaboration with your statistician, develop case report forms to accurately collect data • Why? • Record of participant safety • Record of compliance • Record of procedures carried out • Facilitates analysis of the data and writing the paper(s) • What else???

48. CRF Recording Practices • Do not use records from one subject’s book for another subject. • Do not use photocopies of a CRF as a source doc or as a replacement for a CRF. • If data are not available, record NA. • If a test or item was not done, indicate ND • If no data for a particular CRF is collected, complete the header of the CRF and draw a diagonal line across the entire page to indicate not done. Do not obscure the header section.

49. CRF Recording Practices • Do not write in the margins. • Do not write on the pink or yellow copies of the CRF. Only write on the white page. • Use only black ballpoint pen. • Place cardboard or a similar insert beneath the record on which entries are being made. • Use only standard medical terminology and abbreviations.

50. CRF Recording Practices • Numeric values • Must correspond to source documents. • Must be positioned using the printed decimal where applicable. • It is not necessary to enter zeros in each box. • Times must be recorded using a 24 hour clock. • Complete dates/times should be provided. • When dates/times are unknown, record UNK