1. Research Coordination Guidance The Committees on Human Research Serving University of Vermont & Fletcher Allen Health Care 09-23-111

2.  The following material is intended as guidance on how to achieve good standards and/or best practices in the conduct of research with human subjects.  It is meant to be an adjunct to the basic human subjects protection training information provided in the required on- line tutorial.  The goal is to provide practical advice and tips on how to implement good practices to achieve high quality research results while ensuring the protection of research participants. 09-23-112

3. Good Clinical Practice (GCP) Developed for clinical research, GCP is an international ethical and scientific quality standard applied to human subject research that impacts:  Study design  Conduct  Record management  Data collection and reporting 09-23-113

4. Good Clinical Practice Compliance with GCP standards provides public assurance that the rights, safety and well-being of human subjects are protected and that the study data are credible. Compliance with GCP standards provides public assurance that the rights, safety and well-being of human subjects are protected and that the study data are credible. 09-23-114

5. Applying GCP Standards to ALL Types of Research The principles established by GCP are typically applied to biomedical research, but it is recommended that they also be applied to other studies which have an impact on the safety and well-being of human subjects. This includes research in the behavioral sciences. 09-23-115

6. GCP Objectives  Basic Principles of GCP  Compliance with Protocol  IRB Reporting Requirements  The Process of Informed Consent  Record & Data Management  PI & Research Member Responsibilities 09-23-116

7. Principles of GCP  The rights, safety, and well-being of the research subjects are the most important considerations and should prevail over interests of science and society (E6: 2.3) 09-23-117

8. Principles of GCP  Each individual involved in study conduct should be qualified by education, training, and experience to perform his or her respective tasks (E6: 2.8)  The principal investigator should be qualified by education, training, and experience to assume responsibility for the proper conduct of the study, should meet all the qualifications specified by the applicable regulatory requirements, and should provide evidence of such qualifications through up-to-date CV and/or other relevant documentation requested by the sponsor, IRB, and/or the regulatory authorities (E6: 4.1.1) 09-23-118

9. Principles of GCP  Informed consent should be obtained from every subject prior to study participation (E6: 2.9)  All study information should be recorded, handled, and stored in a way that allows its accurate reporting, interpretation and verification (E6: 2.10) 09-23-119

10. Principles of GCP  The confidentiality of records that could identify subjects should be protected, respecting the privacy and confidentiality rules in accordance with the applicable regulatory requirements (E6: 2.11)  Systems with procedures that assure the quality of every aspect of the study should be implemented (E6: 2.13) 09-23-1110

11. Compliance with the IRB-approved Protocol  A study should be conducted in compliance with the protocol that has received prior IRB approval (E6: 2.6 & 4.5.1)  If you conduct research that deviates from the IRB approved protocol then you are in noncompliance  Serious and continuing noncompliance is reportable to federal regulatory authorities, sponsors and institutional officials 09-23-1111

12. IRB Reporting Requirements  Protocol Amendments  Protocol Deviations  Unanticipated Problems Involving Risks to Subjects or Others 09-23-1112

13. Protocol Amendments  Changes to the study must be submitted for IRB review (E6: 4.4.3 & 4.10.2)  Examples of study changes: –Study procedures –Adding, revising or eliminating measures  Surveys, questionnaires, data collection forms, etc. –Recruitment materials –Study termination, suspensions, and final closure (E.6: 4.12 & 4.13)  Only implement protocol changes after you receive notice of IRB approval 09-23-1113

14. Protocol Deviations  Report promptly to the Committee deviations from the IRB-approved protocol that increase or may increase risk to subjects or others (E6: 4.5.2 & 4.5.3)  Report all other protocol deviations at time of continuing review  Provide an action plan to avoid recurrence –Amend protocol –Create departmental or study specific SOPs 09-23-1114

15. Unanticipated Problems Involving Risks to Subjects or Others (UAPs) Report local events that meet all 3 of the criteria below: 1)Unexpected 2)Related to the study AND 3)Pose harm or a potential for harm to subjects or others (E6: 4.11) 09-23-1115

16. Different Types of Potential UAPs  Physical (e.g. adverse events)  Emotional or psychological harm (e.g., stress and anxiety)  Social harm (e.g., stigma)  Financial harm (e.g., loss of employment or insurability)  Legal harm (e.g., criminal or civil liability)  Invasion of privacy or embarrassment due to breaches of confidentiality 09-23-1116

17. The Process of Informed Consent  Create an Informed Consent Process –Informed consent is not a single event or just a form to be signed –Need a detailed plan that describes the informed consent process  Ongoing Consent –Ongoing discussions regarding the study is imperative in assessing a subject’s willingness to continue study participation 09-23-1117

18. Obtaining Legally Effective Informed Consent  Before informed consent may be obtained, the investigator, or a person designated by the investigator, should provide the subject ample time and opportunity to inquire about details of the study and to decide whether or not to participate (E6: 4.8.7)  All questions about the study should be answered to the satisfaction of the subject (E6: 4.8.7) 09-23-1118

19. Obtaining Legally Effective Informed Consent  Prior to a subject's participation in the study, the informed consent form should be signed and dated by the subject and by the person who conducted the informed consent discussion (E6: 4.8.8)  Prior to participation in the study, the subject should receive a copy of the signed and dated informed consent form (E:6 4.8.11) 09-23-1119

20. Sharing New Information  The informed consent form should be revised whenever important new information becomes available that may be relevant to the subject's consent.  The subject should be informed in a timely manner if new information becomes available that may be relevant to the subject's willingness to continue participation in the trial.  Revised informed consent form(s) or consent addendums must receive IRB approval in advance of use.  The communication of this information should be documented. (E.6: 4.8.2) (E.6: 4.8.2) 09-23-1120

21. Record & Data Management  PI must ensure that research records are: –Accurate –Complete –Legible –Available for audits (E6: 4.9.1 & 4.9.7) (E6: 4.9.1 & 4.9.7) 09-23-1121

22. Data Collection Instruments (DCI)  Review protocol thoroughly to create useful DCIs to collect imperative data points  Forms/instruments must include: –Data collection dates –Subject identifiers 09-23-1122

23. Source Documents  Source documents are original documents, data, and records (i.e. medical records, chart notes, lab reports, memos, subject diaries and checklists, x-rays, pharmacy dispensation logs, etc.)  Data reported on DCIs should be consistent with source documents otherwise discrepancies should be explained and documented (E6: 4.9.2) 09-23-1123

24. Correcting Data  Any changes or correction to data should be –Dated –Initialed –Explained (if necessary) –Do not obscure original data  Example: #010 MMH 6/21/07 #010 MMH 6/21/07 “Subject #001 was seen today, 06/01/2007, for a follow-up study visit. She reported no significant changes since her last visit. She had questions about when she would receive study payments. PI to follow-up with subject regarding her questions.” “Subject #001 was seen today, 06/01/2007, for a follow-up study visit. She reported no significant changes since her last visit. She had questions about when she would receive study payments. PI to follow-up with subject regarding her questions.” (E6: 4.9.3) (E6: 4.9.3) 09-23-1124

25. Maintaining Essential Documents  Essential Documents are those documents which individually and collectively permit evaluation of the conduct of a study and the quality of the data produced.  These documents serve to demonstrate the compliance of the investigator with the standards of GCP and with all applicable regulatory requirements. (E6: 8.1) (E6: 8.1) 09-23-1125

26. Maintaining Essential Documents  Filing essential documents in a timely manner can greatly assist in the successful management of a study.  These documents are also the ones which are usually audited by the sponsor and inspected by the regulatory authorities as part of the process to confirm the validity of the study conduct and the integrity of data collected. 09-23-1126

27. Maintaining Essential Documents  Most Essential Documents are maintained in either the:  Regulatory Binder  Subject Files 09-23-1127

28. Regulatory Binder  Copy of IRB application and all corresponding documents submitted and approved by the IRB  Copies of correspondence to and from the IRB including initial IRB approval letter, copies of consent form(s), assent form(s), parental permission form(s) with IRB approval stamp  Continuing review forms and approvals  Amendment forms and approvals  Copies of any advertisement(s) and IRB approval  Copy of related grant application 09-23-1128

29. Regulatory Binder  Screening Logs  Enrollment Logs  Randomization Logs  Refer to the “Regulatory Binder: Set- up and Maintenance” available on IRB’s Education Website for more detailed guidance on the contents of a typical regulatory binder. 09-23-1129

30. Subject Files  Signed consent forms, assent forms, or parental permission forms  Consent forms may be kept in a secure and separate location from the data, however there must be a key to link consent documents to real data  Source documents (e.g. blood test results or x- rays)  Data Collection Instruments (i.e. forms, surveys) –Proof that all inclusion/exclusion criteria were assessed –Follow-up Assessments –Exit Procedures 09-23-1130

31. Principal Investigator Must Ensure  All persons assisting with the study are adequately informed about the protocol, the investigational products, and their study-related duties and functions (E6: 4.2.4).  Prompt reporting to the IRB of any changes in research activity including any changes to the protocol, and/or consent form(s) and unanticipated problems  No change in approved research may be initiated without the IRB’s approval except under conditions where it is necessary to eliminate apparent immediate hazards to human participants 09-23-1131

32. Members of the Research Team Must:  Adhere rigorously to the IRB approved protocol  Inform PI of all unanticipated problems  Ensure the adequacy of the informed consent process  Take measures necessary to ensure adequate protection for subjects 09-23-1132

33. Useful Tools The following tools are available on the IRB’s Education Website: The following tools are available on the IRB’s Education Website: –Regulatory Binder: Set-up and Maintenance –Human Subjects Protection Program: Investigator Self-Assessment 09-23-1133

34. References  Good Clinical Practice: Consolidated Guideline ICH Topic E6 09-23-1134

35. Where to go for more Information? We are here to help! University of Vermont Research Protections Office 213 Waterman Building 85 South Prospect Street Burlington, Vermont 05405 (802) 656-5040 http://www.uvm.edu/rpo/ 09-23-1135