Regulatory Document Guidelines for DMID Clinical Studies. Version Oct-2005

Transcription

1 Regulatory Document Guidelines for DMID Clinical Studies Version Oct

2 Regulatory File Document Guidelines Purpose: To aid DMID supported Investigators in establishing a file of essential documents 2

3 Regulatory File Document Guidelines Investigators must maintain 1 file for each study, and all essential documents must be in the file Must be established at beginning of each study Updated throughout life of study Source for Guidelines ICH/GCP at 21 CFR 11, 50, etc. at 45 CFR 46 at 3

4 Definition Essential Documents Are documents that permit evaluation individually and collectively of the conduct of a trial and the quality of data produced Demonstrate compliance of investigator, Sponsor and monitor Confirm validity of trial conduct Maintain integrity of data»ich Guidelines Section 8 4

5 Table of Contents a. Abbreviations b. Essential Documents c. Essential Documents Maintenance List General Study Guidelines IRB Regulatory Submissions IRB Safety Submissions Licenses/Accreditations Correspondence/Notes Other Documents to File This is not meant to be all encompassing 5

6 Table of Contents 6

7 Sample Forms Study Identification Study Personnel Signature/Responsibility List Screening/Enrollment Log ID Code List Receipt of Test Article Test Article Accountability Record Investigational Drug Accountability Record Investigational Vaccine Monitoring Form Disposition of Test Article at End of Trial Temperature Logs Monitor Log Regulatory Review History Log Protocol Deviation Telephone Contact Report 7

8 Document Maintenance Where do your regulatory documents need to go? Do they need to go in more than one place? (i.e.; site regulatory file, ORA at DMID, IRB/IEC) 8

9 Study Identification This section will contain: Identification of Site Name of Principal Investigator (PI) Location(s) DMID Protocol Number (include IRB/IEC number if different from Protocol number) IND Number Protocol Title 9

10 Study Identification Form 10

11 Study Identification Form Complete a new form when any information changes Retain a copy of previous version in Regulatory Files Complete a Study Identification Form for each Protocol at each separate study site 11

12 Federalwide Assurance (FWA) Obtained by individual institution for their IRB Maintain a record of Federalwide Assurance (FWA) number and expiration date Web site for obtaining this information: 12

13 Form FDA 1572 Signed/dated by Principal Investigator List names of all Sub-investigators Location of all sites where Subjects are seen Section 4: List Clinical Laboratories ONLY Research Laboratories must be identified in Protocol 13

14 Form FDA 1572 Section 8: Nine commitments of the investigator 14

15 Form FDA 1572 Hand signed/dated on a double-sided form Keep ORIGINAL at site Complete a new form when there is a: Change in Principal Investigator Change in Sub-investigator Change in address of Study Site Change in Clinical Laboratory Change in IRB 15

16 Awareness Check Who obtains the FWA? What are the Nine Commitments of the 1572? Do you know how your essential documents get to ORA at DMID? 16

17 Study Personnel Signature/ Responsibility List Records signatures and initials of all study personnel including: PI Sub Investigator Study coordinator Pharmacist Lab workers Keep list current 17

18 Study Personnel Signature/ Responsibility List 18

19 Study-Specific Procedures or Manual of Procedures May include: Lab Procedures, Lab Specimen/Test Article handling and/or preparation instructions, and Protocol-specific instructions Each Study-Specific Procedure or Manual of Procedures (MOP) must have Version Number and Date All versions must be maintained in the Regulatory File 19

20 Subject Screening/ Enrollment Log All Subjects screened for the study must be on the screening/enrollment log A study number or screening number must be used List reason Subject was not enrolled when applicable Minority and gender data must be collected per NIH policy for all Subjects enrolled Subjects must not be screened until they have signed an Informed Consent document 20

21 Subject Screening/ Enrollment Log 21

22 ID Code List Study use only Contains names of all Subjects allocated study numbers upon enrollment Contains Subject contact information Allows investigator/institution to reveal the identity of any Subject Confidential document Remains at the site 22

23 Test Article Accountability Records The following documentation MUST be included with the Essential Documents: Shipping receipts Receipt date Quantity Lot numbers Copy of test article label 23

24 Test Article Accountability Records 24

25 Test Article Accountability Records Records must show during the study: date the test article dispensed the amount used date and quantity of the study drug returned by Subjects Records must show at end of study: Test article is returned to appropriate place or destroyed Date of shipment or destruction Quantity Lot number 25

26 Test Article Accountability Records Physical inventories are recommended on a monthly basis Maintain records to verify cold chain for all materials stored at other than room temperature (Temperature Logs and Records) 26

27 Test Article Accountability Records Keep copy of Test Article Sample Label (ICH GCP ) Keep copy of any drug purchased locally, vaccine, diluent or placebo label 27

28 Test Article Accountability Records Never destroy test article vials/containers until the monitor has completed accountability unless directed specifically to do otherwise Disposition of any unused vials remaining at end of the study will be determined by the DMID 28

29 Test Article Accountability Records Transfer of test article from one study to another is not allowed For blinded studies, expiration dates and lot numbers are confidential and are not entered onto the Accountability Log 29

30 Awareness Check Who should monitor test article accountability for a blinded study? Does your institution have a standard operating procedure for checking the refrigerator temperatures? What about documenting ranges? 30

31 Temperature Log Maintain a separate temperature log for all refrigerators/freezers that hold study related materials 31

32 Temperature Log 32

33 Monitor Log/Monitoring Reports List all study site visits made by external monitors Retain a copy of all site visit letters and reports Any correspondence concerning site visits with the site monitor or Sponsor should be here 33

34 Specimen Retention Records Maintain a record of retained body fluids/tissue samples (if any) Sites must consult with DMID regarding the relocation, destruction, or anonymization of any specimens at the end of the trial Unused specimens must be destroyed or anonymized unless consent has been granted for future use of stored specimens 34

35 Paper CRF Include a blank copy of all final versions of the CRF, subject diaries, or other forms for entering the study data. 35

36 Electronic CRF All versions of the source document workbook should be in this section Dated documentation of all changes to the database must be maintained in this section At the end of the trial, a CD, disk, or hard copy of all final versions of ecrfs must be added to the file 36

37 CRFs used as Source Documents Per ICH GCP 6.4.9, the protocol should have a description of the trial design that should include: The identification of any data to be recorded directly on the CRFs (i.e. no prior written or electronic record of the data) and to be considered source data. 37

38 Awareness Check How is information shared at your site between lab staff, pharmacy staff and study staff? Who maintains documentation considered essential documents for your research pharmacy, lab? 38

39 Regulatory Review History A running log that should include: All documents submitted to IRB/IEC, version number/date, description of change, and the date of submission Separate entry for each submission 39

40 Regulatory Review History 40

41 Submission Letter/Package IRB/IEC Approval Includes: Full copies of original IRB-approved Protocol, subsequent approved revisions/amendments to Protocol Keep entire packets together in the file, including submission letter/package, responses, comments, and final IRB approval Everything must have a Version Number and date 41

42 IRB Approval Letter At minimum: (per GCP guideline 3.1.2) DMID Protocol name and number Approval date List of approved documents In addition, DMID suggests: IRB chair or designee signature Addressed to PI List all sites covered by approval Version number and date documents submitted 42

43 Protocol/ Protocol Amendments Retain original IRB/IEC approved Protocol and any approved revisions/amendments Draft Protocols that were not submitted do not need to be maintained Remember to include version numbers and dates If the PI, sub I, or study coordinator is a member of IRB/IEC, documentation must be in the file of voting abstention for all approvals relating to this protocol 43

44 Consent Forms Include a copy of original IRB-approved consent and any subsequent IRB-approved revisions/ amendments Other consent forms: Screening consents Future use consents Translated consents 44

45 Collaborating Research Laboratories If identifiable samples are to be sent to a collaborating lab for research, IRB approval must be obtained by the site s IRB and the collaborating lab s IRB Documentation concerning the samples sent to the collaborating lab must be maintained in the regulatory binder 45

46 Identifiable Samples Any specimen linked to subject identity by a readily available identifier such as name, social security number or coded number that links the sample to their source through a key available to the investigator or collaborating lab 46

47 Advertisements and Subject Information Materials Types: TV Radio Newspaper Internet Flyers IRB approval must be obtained prior to the use of any study advertisement including revisions to advertisements 47

48 Investigator s Brochure/ Package Insert Must be available to all study staff This is the site s reference to potential reactions and side effects IND Safety Reports must be filed with the Investigator s Brochure Any other informational letters issued by the manufacturer must be filed with the Investigator s Brochure 48

49 Periodic Reports/Annual Renewals Final Reports Reports are submitted by the Principal Investigator to the IRB including: New safety information DSMB reports Annual renewals Final report Maintain all approval letters with documents that were submitted 49

50 Non-U.S. Regulatory Approvals Non-U.S. authorizations relating to the Protocol should be maintained Must have documentation of approval from country in which study takes place for studies conducted outside the United States Approvals must be collected/renewed per entity s regulations 50

51 SAE Reporting Maintain copies of all SAE report forms in your Regulatory Binder IND Sponsor may also send sites IND Safety Reports these also must be submitted to the IRB and maintained in the regulatory binder 51

52 Protocol Deviation Reporting DEVIATION = ANY non-adherence to the Protocol Deviations may include issues with: Informed Consent Enrollment Occurrences of non-adherence to the Protocol DMID does not allow exemptions or eligibility criteria waivers for enrollment 52

53 Protocol Deviations Must be addressed in source documentation Include reason, attempts to prevent or correct A deviation form must: Be completed for each Protocol deviation Be sent to DMID (refer to Source Documentation Standards for specific reporting requirements) Be copied and maintained at the site, in Subject s source documents, Regulatory File Notify your IRB per IRB s requirements 53

54 Protocol Deviations 54

55 Curricula Vitae Curricula Vitae: Needed for Principal Investigator and all Sub- Investigators Must be dated within 5 years of the current date Basic requirements: Current work address Professional title Degrees Current relevant licensure 55

56 Medical Licenses Provide a copy of the PI s current medical license. If the PI is not an MD, a medically responsible physician must be identified and a current license collected Maintain a copy of current medical licenses for the PI and all sub-investigators listed on the Form FDA 1572 in the regulatory file 56

57 Laboratory Normals and Accreditations Sites must maintain current lab normal ranges used by all clinical laboratories for study data Laboratory name and effective date of the laboratory normals must be provided Sites must maintain a copy of all current laboratory certifications 57

58 Laboratory Normals and Accreditations Domestic laboratory certifications should include: CLIA of Accreditation and a private agency certification (i.e. CAP or JCAHO) or CLIA of Compliance (stand alone), or Department of Health Certificate (if CLIA-exempt state) 58

59 Laboratory Normals and Accreditations For Research Laboratories, no accreditation is required CLIA exemptions exist for certain tests For non-u.s. laboratories, national equivalent of certification must be included 59

60 Correspondence and Notes to File Site Correspondence with the DMID/Sponsor Internal Correspondence Notes to File Site Specific Information Clinical Database Validation 60

61 Telephone Contact Report 61