IRB-GCP and Timelines. Andrew Majewski, MSc. 1 st DOLF Meeting Washington University School of Medicine St Louis, Missouri-USA October th, 2010

Transcription

1 IRB-GCP and Timelines Andrew Majewski, MSc. 1 st DOLF Meeting Washington University School of Medicine St Louis, Missouri-USA October th,

2 Factors that affect Timelines Finalized Protocol Finalized Case Report Form (TBD) Finalized Consent Country Dependent Selected Sited (TBD) Qualified Investigators Local US Federal Wide Assurance Registration (RCTs?) IRB Identification IRB Protocol Approval Drug and Importation Permit Institutional Certifications GCP Training (FHI) Equipment and Materials Logistics Monitors Timing: Seasons 2

3 It is easier to develop good habits than to correct bad ones -Anonymous 3

4 Overview: ICH (International Conference on Harmonisation) Guidance document developed within a multicountry expert working group Sets an international standard for the conduct of human trials, which governments can transpose into regulations for clinical trials involving human subjects ICH Homepage: FDA Homepage: es/ucm htm 4

5 Certification and Resources: All members participating in the trials, RCT or not, must obtain online training/certification from their respective institution. Other resources: The Office of Human Research Protections (OHRP) Belmont report: Helsinki report (1964; current version 2008): 5

6 Ethical Review Committees (ERC) 6

7 Ethical Review Committee (ERC) Responsibilities Types of Ethics Committees/Boards Role: Safeguards the rights and safety and well being of all trial volunteers. Pays particular attention to special populations Local-IRB/ERC/IEC National Ethics Committee (NEC) Ministry of Health (MoH), if appropriate In parallel (independent review) Sequential (after an EC has approved the study) 7

8 Guidance of ERCs ICH GCP Section 3 WHO GCP Annex 3 section 3.2 WHO- Operational Guidelines for EC that Review Biomedical Research, Geneva, 2000 WHO Surveying and Evaluating Ethical Review Practices, Geneva,

9 What does the ERC need to do? Meet regularly Follow established procedures Conduct continuing review of each protocol at a minimum of once per year Consider the PI s qualifications Request more information to be provided to the volunteers as needed. Review amount and method of payment 9

10 Documents obtained from the ERC Protocol/amendments Consent forms Recruitment plans Written information provided to volunteers Investigator Brochure Volunteer Compensation Modifications to documents Other documents Approval/Disapproval letters Termination letters Investigator CV 10

11 Who serves on ERCs? Membership should be well balanced for different expertise to review: Scientific contents Medical Aspects Ethical considerations Composed of at least 5 members for a quorum (7-8 is best) One member should non-scientific One member who is independent of the institution or trial site. At least 1 woman 11

12 What should the ERC procedures include? Follow written procedures Document meeting minutes and circulate the results to the PI and Sponsor. Make decisions at announced meetings with at least a quorum. Require voting members to participate in protocol review and discussion Invite non-members for expertise and advice when needed. 12

13 What should the ERC procedures include? Names and qualifications of members A charter-guideline for scheduling, notification and conduct of meeting. Determined frequency to review protocols Initial and continue review of protocols Set term limits, if applicable Promptly provide meeting results, decisions and procedures for appeal to the PI as appropriate. 13

14 What should ERC ask of PI s? PI s are to promptly provide the following: Deviations or changes to the protocol Changes that increase risks to volunteers All AE s that are serious and unexpected New information that might adversely affect the safety of the volunteers. 14

15 What records should be maintained by the ERC? The following Records must be retained for > or equal to 3 years: Written procedures Membership lists List of members occupation and affiliation (to reduce COI) Submitted documents Meeting minutes Correspondence 15

16 Communications Regulatory Sponsor Investigator Ethics Committee 16

17 Investigator Responsibilities: Communication with ERC ICH GCP 4.4 Before the trial begins, obtain written and date approval of the following from the ERC: Protocol Consent Forms Recruitment procedures Written information provided to subjects Investigator Brochure (IB) During the trial, provide the ERC with all the documents required/ requested for review 17

18 Good Clinical Practice (GCP) 18

19 Good Clinical Practice (GCP) ICH Section E6 International standard for Ethical and Scientific quality for: Trial design Trial conduct Protection of human rights as a subjects in the trial Define the roles and responsibilities of the sponsors/investigators/monitors Recording and reporting in trials involving human subjects Website: C pdf 19

20 General Instructions for GCP Write legibly in black or blue ink Complete all sections of the form If the data is missing, write missing. Dates are in ddmmyyyy (i.e. 05OCT2010 ) If a change needs to be made, one line across the incorrect information, followed by initials and date as described above 20

21 Protocols & Informed Consent 21

22 What is a Protocol? A Clear and detailed PLAN of a scientific experiment Describes the PURPOSE of the study Defines the STUDY ENDPOINTS Explicitly describers EVERY PROCEDURE 22

23 The Protocol includes One Primary Objective with Primary & Secondary endpoints A Treatment Schedule Inclusion/Exclusion Criteria Screening Procedures Enrollment Procedures 23

24 The Protocol Includes Supplemental material: Investigator Brochure (IB) Study Operations Manual (SOM) SAE Manual Changes to the protocol can only be done with written amendment and ERC approval Protocol Compliance: To assure the protocol is done consistently and accurately regardless of geographical location. Ensure the safety of the volunteers as well as the integrity of the data. 24

25 What is different in a Clinical Trial? Investigator works within the parameters of the protocol Structured assessments Structured documentation: Source Docs/ CRFs Structured reporting requirements Structured guidelines 25

26 Structured Safety Assessment and Documentation Factors: Protocol dependent Forms correspond with the protocol Forms drive the assessment Multiple forms exist (DCF/ CRFs) Form Completion is the primary way to ensure safety and the quality of data 26

27 Informed Consent 27

28 The Term Consent Consent is the agreement of the volunteer to participate in the screen (screening consent) and/or protocol (protocol consent). Considered more than a signature or an agreement. A promise from the research team to the volunteer. OBTAINED BEFORE ANY PROCEDURES ARE DONE WAIVER of Documentation for informed consent for minimal risk epidemiology projects 28

29 Informed Consent: A process, Not a Just a Form When does the Process begin? ICH GCP Guidelines : Describes the consent process and a clear list of topics (a-t). What does it really mean? The volunteer is provided all available information about the trial and the volunteer demonstrates understanding. 29

30 Why Document the process? Chronicles the effort in obtaining true informed consent. Demonstrates compliance with guidance principles Makes good medical sense. Promise to conduct the trial as described/ informed. The process ensures volunteer safety during trial participation. IF IT S NOT DOCUMENTED, IT S NOT DONE 30

31 Consent Material & Communication Must be accurate and complete Corresponds to the protocol and consent form Can be written, verbal, visual information Informational summaries Discussion and informational seminars Illustrations and Diagrams Approved by the Ethics Committee Document everything Don t overpromise or oversell-this remains research 31

32 What are the Elements of Informed Consent? ICH GCP Guideline The study involved Research You are being asked to participate in a clinical research study to The study has a Purpose The goal of this study is to evaluate if product XYZ and evaluate the response to XYZ 32

33 What are the Elements of Informed Consent? Describes the following: Main parts of the study: The procedures to be followed and the volunteers responsibilities Duration and Assignment Risks: Describes reasonable foreseeable risks or inconveniences to the volunteer Benefits: Describes reasonable expected benefits to volunteer or others 33

34 What are the Elements of Informed Consent? Describes the following: Alternatives: Discloses appropriate alternatives procedures if available Confidentiality: Describes the extent of the confidentiality of records identifying the volunteer Compensation: The compensation and/or treatment available to the volunteer in the event of a trial related injury. 34

35 What are the Elements of Informed Consent? Describes the following: Contact Information: Provides the names and phone numbers of the people to contact about more information on the trial, their rights, and in the event they incur a trial-related injury Volunteer Participation: The right to withdraw as any time without penalty Termination of Participation: Foreseeable circumstances and/or reasons under the which participation in the trial might be terminated 35

36 What are the Elements of Informed Consent? Describes the following: New Findings: Informed in a timely manner if information becomes available that might be relevant to the volunteer s willingness to continue participate in the trial Number of Volunteers: The approximate number of volunteers in the study 36

37 Is the volunteer Bound to the Consent Form Agreement? The built in options for the volunteer to: Withdraw at any time with out any penalty Right to contact various bodies if they are harmed or treated incorrectly Right to new information that might affect their willingness to continue 37

38 Summary of Informed Consent The trial purpose, product used, number of volunteers Randomization plan, if applicable Procedures Expectations of their participation Potential and theoretical risks Benefits (if any) Compensation (if any) 38

39 Review the Protocol Consent Form Insure the validity date by the IRB Review and provide the opportunity to ask questions The right to withdraw at any time If they agree, the Volunteer must include the following: Print Name Provide Signature by Volunteer Date of willing participation (ENROLLED) Signature by Witness with date on the same day (usually someone else who delivered the message but associated with the project) Copy of their Consent form to the volunteer 39

40 Safety & Documentation 40

41 Who s interested in this Safety Reporting? Sponsor and Investigative Team Ethical Review Committee (IRBs) Data Safety Monitoring Board (DSMB) Subjects, Participants, Volunteers Community leader or Community Advisory Boards (CABs) Local Office for Ministry of Health (MoH) 41

42 Trial Development: Safety during Protocol Performance Documentation = Accountability Drug accountability Subject enrollment: Consent Form Subject Monitoring: Case Report Forms Safety Data Reporting: SAE Reporting/ DSMB 42

43 Safety Related Documentation Enrollment Monitoring Data Reporting 43

44 SAE: Serious Adverse Event SAE is defined as: An adverse event is any undesirable experience associated with the use of a medical product in a patient. All need to be reported even if not apparently related to test article Death Life-Threatening Hospitalization (initial or prolonged) Disability Congenital Anomaly Requires Intervention to Prevent Permanent Impairment or Damage 44

45 Documentation Maintain all of the following in a fire-proof filing cabinet (locked room, locked cabinet) FWA registration recommended to assure compliance with international standards Standard Operating Procedures (SOPs) Data Collection Forms (i.e. CRF) Volunteer information Forms Signed consent forms (Exceptions) 45

46 Documentation ICH 8: Maintain the following in the Regulatory File All versions of documents from beginning to trial end Information given to subjects Financial aspects of the trial Insurance statement for the protection and treatment of human subject (FWA) Signed agreements between institutions, PIs and CRO Dated, Documented Approval ERC (Regulatory, if applicable) letters including minutes of meetings CVs on all staff personnel including the local PI. 46

47 Trial Timeline Overview 47

48 Trial Timeline Overview Idea Protocol Development Protocol Finalize US & Local Certification Site Initiation Visit Begin Trial (FPFV) Product TIME Grant Site Selection Under Our Control NOT in Our Control Contracts IRB Approval Federal (MoH) Wide Assurance USA-IRB and Country IRB Site Qualification Visit (SQV)?? Registration???? Drug and Drug Importation 48

49 Trial Timeline Overview Trial Begins (FPFV) TIME Sampling LPFV LPLV Site Close-Out STOP Amendment (Requires IRB Approval) Monitoring Auditing Annual IRB Review (MoH) 1ºData Analysis Under Our Control NOT in Our Control USA-IRB and Country IRB FPFV FPLV LPFV LPLV 49

50 Trial Timeline Overview Idea Product Protocol Development Finalized Protocol US & Local Certification Site Initiation Visit Begin Trial (FPFV) TIME Grant Site Selection Under Our Control NOT in Our Control Contracts IRB Approval Federal (MoH) Wide Assurance USA-IRB and Country IRB Site Qualification Visit (SQV)?? Registration???? Drug and Drug Importation 50

51 Thank You 51