Verifying Source Documents

2 Source Documentation First place the data are captured Original documents, data, and records Certified Copies Should contain certain specific information about the participant and trial

3 Working Definition of Source Documents This information consists of all written and printed documents that are pertinent to a research participant’s: exposure to the investigational agent(s) exposure to other treatments progress of the disease course response to therapy

4 Source Document Examples Physician Progress Notes Nurse’s Notes Diagnostic Test Reports Medication Records Laboratory Results Participant Diaries

5 CORRECTIONS Four items must be visible each time a raw data value is changed: (1) The old value (2) The new value (3) The date of the change (4) By whom the change was made. [ the reason for the change must either be apparent or an explanation provided]

6 Addenda/Insertions When text needs to be inserted, it cannot be squeezed between lines or in margins. Insertions should be documented as a signed addendum and placed after the last entry.

7 Protecting Subject Identity Source Documents full name Documents for Sponsor/Data Mgmt. Participant initials randomization number date of birth (optional)

8 Case Report Form Tool to collect the data and provide condensed picture of participant’s involvement in the study Not intended to replace Source Documents Investigator’s responsibility

9 Ensure Good Documentation by Knowing Your Study Protocol Investigator Brochure Case Report Form guidelines Lab procedures Medication Requirements Sponsor requirements Regulations

10 What the Monitor will verify GCP and Federal Requirements (ICH, OHRP, FDA) Sponsor requirements Protocol Adherence “We monitor by the protocol”

11 Verifying Source Documents Ensure that source data is complete, accounted for, follows a logical sequence of events, and that source data supports entries in CRF

12 Performing Logic Checks Recreate the scenario: who did what, when, where, how, and why Determine the impact an event has elsewhere (med. hx., con. meds., AEs) Note inconsistencies Dr. notes no complaints Nurse documents multiple complaints from same subject on same day

13 Protocol Required Documentation All inclusion/exclusion criteria addressed Study required tests and procedures done on time or if not, why not Withdrawals, dropouts, lost to follow up AEs/SAEs properly documented/reported Endpoints of the study

14 Access to Source Documentation Investigator’s responsibilities IRB/IEC Sponsor contractor of the sponsor such as PPD Regulatory agency (FDA, OHRP) Investigator agreement and informed consent authorize access to records

DAIT Source Document SOP

16 DAIT Source Documentation SOP Data must be verifiable Needs an audit trail ALCOA* Attributable, Legible, Contemporaneous, Original, Accurate *Source: “The Facts About Source Documents” »Stan Wollen, Presented at 1999 DIA Mtg..

17 DAIT SD SOP Format SD specific item noted Requirement Suggestions Reference

18 DAIT SD SOP Addenda Assent CRFs as SD Chart Note Communications written verbal

19 DAIT SD SOP Compliance: study drug/agent Computer Records Concomitant Medication: non-study Confidentiality Consult Notes

20 DAIT SD SOP Contraception: protocol required Copies: certified Death Deviations/Violations Documentation Standards Endpoints Entry Criteria (Inclusion/Exclusion)

21 DAIT SD SOP Error Corrections Flow Sheets Identifiers Informed Consent Initials

22 DAIT SD SOP Lab Tests: Specimen Collection Lab Tests: Results Medical History Medical Records Prescriber Prescriptions

23 DAIT SD SOP Procedures: Diagnostic, Therapeutic, Surgical, etc. Questionnaires Research Record Source Document Storage of Source Documents

24 DAIT SD SOP Study Drug/Agent Study Drug/Agent Accountability Toxicities: grading (adverse events, signs and symptoms, lab results) Transferring Subjects Vital Signs and other Assessments

DAIT Source Document Site Training Questions

26 Computer/Electronic Records Is the site required to have hard copies of all patient related data in order to ensure proper monitoring? What questions will the monitor ask if they are observing subject data via a computer?

27 CRFs as SD A CRF that is being used as the SD has multiple data entries and one signature at the end of the form. Would this ever be acceptable and if so, provide specifics.

28 CRFs as SD Is it acceptable for the site to use the SAE report form as their SD of a serious adverse event? Explain the specifics.

29 Certified Copies The site has received a discharge summary via fax from a health care facility where a study subject was treated over the weekend for angina. The fax is difficult to read and looks as if some information has been covered with correction fluid (white-out). Should the coordinator certify this copy? What does the certification mean?

30 Error Corrections When would it be necessary to explain why data were changed or corrected? Provide an example.

31 Informed Consent A new version of the consent form for your study was available but enrollment at your site was completed and participants were in the follow up phase. Should you obtain the new consent form, obtain IRB/IEC approval and ask participants to sign it?

32 Informed Consent Subject who is illiterate makes his mark on the consent form in the space for subject signature. List at least three things that need to be verified with regard to this special situation.

33 Informed Consent Who is required to sign the consent form? Provide a variety of possible answers to this question based on multiple scenarios.

34 INFORMED CONSENT The subject refuses to take a copy of the consent form and says that she does not want her husband to know that she is participating in this trial. What should be documented about this? PATIENTINFORMED CONSENT CONSENT FORM FORM

35 Medical Records List the reasons why a monitor would ask the site to attempt to obtain subject medical records if they were not present in the research record.

36 Reportable Events The monitor discovered that a grade 4 event has not been reported. The coordinator stated that this event was not related to drug (though no documentation exists re: R/T drug). The investigator suggested that perhaps this event was “misgraded”. How should the monitor and site personnel resolve this?

37 Toxicities What possible actions should site personnel take upon the discovery of laboratory toxicity? Provide multiple scenarios.

38 Inconsistent SD The study nurse writes something in the SD that conflicts with what an investigator has written. What should be the response of the site personnel who discovers this discrepancy?

39 Who needs to be included? Investigator of Record Agreement CVs

40 IRB/IEC ISSUES The DAIT/DAIDS 000 protocol approval is from 02 Oct Oct03. The study coordinator received a notice from the IRB that an extension has been granted due to a delay in the meeting date. What should the coordinator do?

41 IRB ISSUES What documentation should be on file if the PI is a current, voting member of the IRB?

42 ERROR CORRECTIONS An informed consent was signed 07 Jun 03 after which all relevant study investigations were carried out. The research record indicated that the consent was signed on 08 Jun 03. How will you rectify this?