Investigator Responsibilities & Research Protocol

1. Investigator Responsibilities & Research Protocol K. Lynn Cates, M.D. Assistant Chief Research & Development Officer Director, PRIDE HRPP 101 January 26, 2011 (revised 2/3/11)

2. Investigator • Any individual who conducts research involving human subjects including, but not limited to • Principal Investigator (PI) • Co-PI • Local Site Investigator (LSI) 2

3. VA Investigator • Any individual who conducts research approved by a VA Research & Development Committee including • VA appointment on VA time • Full & part-time VA employees • Without compensation (WOC) VA employees • Appointed or detailed to VA under the Intergovernmental Personnel Act (IPA)

4. Principal Investigator (PI) • Qualified person designated by an applicant institution to direct a research project or program • Usually writes the grant application • Oversees management of all project activities • Scientific • Technical • Day-to-day • If more than one investigator on a study, PI is the leader

5. Co-Principal Investigator (Co-PI) • One of two or more PIs who share equally in accountability for a study • Must have same qualifications as PI

6. Local Site Investigator (LSI) • An investigator at a site participating in a multi-site project • Oversees management of local site activities • Scientific • Technical • Day-to-day

7. Investigator Responsibilities • Upholding professional & ethical standards & practices • Adhering to all applicable requirements for conduct of research & the protection of human subjects • VA • Other Federal requirements • Local VA facility’s Standard Operating Procedures (SOPs), • Responsibilities may be defined in the protocol or IRB application • Some of responsibilities may be assumed by an investigator working under the PI 7

8. Conflict of Interests (COI) • Disclosing to the IRB any potential, actual, or perceived conflict of interest that may affect any aspect of the research including • Financial • Professional • Personal nature • Complying with all other applicable VA & other Federal requirements regarding conflict of interest 8

9. Ensuring Adequate Resources • Ensuring there are adequate resources to carry out the research safely • Sufficient investigator time • Appropriately qualified research team members • Equipment • Space 9

10. Ensuring Research Staff Are Qualified • Ensuring appropriate • Training • Education • Expertise • Credentials • Privileges, when relevant • Identifying study team members by name or by title in protocol • IRB may require specific individual(s) by name 10

11. Replacing Qualified Staff in IRB-Approved Protocol • Replacing a team member identified in the IRB-approved protocol by name • Requires IRB approval of an amendment • Replacing a team member identified in the IRB-approved protocol by title • No IRB approval is required if replaced by someone with the same title 11

12. Reporting Changes in Research Staff to the IRB • Promptly reporting changes in PI, LSI, Co-PI, or Co-LSI • IRB must evaluate & approve to ensure the new individual meets the criteria described in 38 CFR 16.111 • Reporting changes in other key research staff at the time of continuing review, or sooner if required by local SOPs • Additions to staff • Loss of staff 12

13. Overseeing the Research Staff • Ensuring research staff • Comply with all applicable requirements • Implement the study in accordance with the IRB-approved protocol 13

14. Research Protocol • Contains all required information • Research is scientifically sound • Research is in compliance with all applicable VA & other Federal requirements, & local SOPs 14

15. Research Protocol • Recruitment plan is just, fair, & there is equitable recruitment & selection of subjects • Minimizes risks to the subjects or others • Contains a data & safety monitoring plan for prospective studies • Data Monitoring Committee (DMC), if relevant • Enlists clinicians with expertise & privileges • To review data, adverse events, new study findings • To make decisions to protect the health of the subject 15

16. Research Protocol • Clearly differentiates the research intervention(s) from “usual care” – subjects need to know • What is research vs. usual care? • Who explains risks & benefits? • Who provides the treatment or services? • Who monitors the treatment or services? • Are the AEs from research or usual care? • Who alerts the subject if there is a problem? • Who documents the subject’s clinical course? 16

17. Research ProtocolPrivacy & Information Security • Dedicates specific sections of the protocol or develops an additional document to address: • Privacy & confidentiality • Information security 17

18. Research ProtocolReuse of Data • If data may be reused in other studies • Description of data repository • Research informed consent & HIPAA authorization (unless waived) • Uses & disclosures of data • How privacy & confidentiality will be maintained • How the data will be secured

19. Research ProtocolVulnerable Subjects • Provides for protection of vulnerable subjects • Describes special safeguards

20. Obtaining Written Approvals Before Initiating Research • Investigator must obtain all approvals in writing from the IRB, all other committees (e.g., R&D Committee), subcommittees, & other approvals • Investigator cannot initiate research at a given site without written notification from the local ACOS for R&D(VHA Handbook 1200.01) • For multi-site studies, the LSI cannot initiate research without approval in writing from the local ACOS for R&D 20

21. Implementing the Study as Approved by the IRB • Ensuring the study is implemented • As approved by the IRB • In accordance with other required approvals & with all applicable local, VA, & other Federal requirements • In accordance with FDA, when applicable 21

22. Investigator’s Research Records • Maintaining documentation that the protocol is being implemented • As approved by the IRB • In accordance with other required approvals • Documents will be audited 22

23. Informed Consent • Obtaining & documenting informed consent prospectively • Investigator cannot screen, interact, or intervene with a subject until after meeting the IRB-approved informed consent requirements • Exceptions • IRB determines the research is exempt • IRB approves a waiver of informed consent • IRB approves a waiver of documentation of informed consent form 23

24. Informed ConsentDesignee • If the PI or LSI does not personally obtain informed consent • Formally & prospectively designating in writing in the protocol or the application • By name • By title • Designee must • Be a member of the research team • Receive appropriate training • Be knowledgeable enough about the protocol to answer the questions of prospective subjects 24

25. Informed Consent • Using the most current IRB-approved version of VA Form 10-1086 • Providing the prospective subject or the Legally Authorized Representative (LAR) sufficient opportunity to consider whether or not to participate • Minimizing the possibility of coercion or undue influence • Clearly defining potential risks • Advising subjects to review the risks of usual care with their health care providers 25

26. Obtaining Informed Consent • Ensuring the documentation includes • Signature & date of the subject or LAR • Signature & date of the person obtaining the informed consent • The signature & date of witness, when applicable • Subject may submit the signed & dated informed consent form by facsimile, if approved by IRB • Ensure all original signed & dated forms are in the investigator’s research files, readily retrievable, & secure 26

27. Consistency • Ensuring consistent language in • Protocol • Informed consent form • HIPAA authorization 27

28. Obtaining HIPPA Authorization • Obtaining HIPAA authorization for the use & disclosure of the subject’s Protected Health Information (PHI), or obtaining a waiver of HIPAA authorization • Obtaining & using real Social Security numbers only when required to meet the specific aims of the research protocol or to enter information into the subjects’ health records 28

29. Performing Subject Outreach • Making every reasonable effort to make available the informational brochure, “Volunteering in Research – Here Are Some Things You Need To Know” http://www.research.va.gov/programs/pride/veterans/tri-fold.pdf • Ensuring informed consent forms provide subjects with required contact information for • VA investigator & relevant study staff • A contact independent of the research team 29

30. Ensuring Appropriate Telephone Contact with Subjects • VA prohibits requesting Social Security numbers by telephone • Initial contact with potential subject must be in person or by letter prior to initiating any telephone contact • Unless there is written documentation that the subject is willing to be contacted by telephone about the study in question or a specific kind of research • Initial contact must provide a telephone number or other means that the potential subject can use to verify the study constitutes VA research 30

31. Ensuring Appropriate Telephone Contact with Subjects • Ensuring the research team begins telephone calls to the subject by referring to • Previous contacts • Information provided in the informed consent form (if applicable) • Ensuring the scope of telephone contacts is limited to topics outlined in IRB-approved protocols & informed consent forms 31

32. Obtaining IRB Approval for All Changes • Obtaining IRB approval for all changes to the research prior to implementing the changes • Amendments or modifications to the protocol • Changes to the IRB-approved informed consent form • One exception • Eliminating apparent immediate hazard to the subject • Promptly reporting these changes to the IRB 32

33. Continuing Review • Providing the IRB sufficient time for reviewing & approving the study before the IRB approval expires • IRB approval automatically expires if the continuing review & approval does not occur by the expiration date of the current approval • Understanding responsibilities if approval expires 33

34. Reporting Deviations, Complaints, Problems, & SAEs • Reporting deviations from the protocol & subject complaints to the IRB in a time frame specified by • Local SOPs • ORO • Reporting all unanticipated problems involving risks to subjects or others, & all unanticipated internal (i.e., local) SAEs, whether related or unrelated to the research, in accordance with local SOPs & VHA Handbook 1058.01* *See ORO website: http://www1.va.gov/oro/ 34

35. Project Completion • Completing all required documentation • Storing research records according to all applicable VA & Federal records retention requirements • Communicating the results to subjects or the community from which subjects were recruited (if appropriate) 35

36. Departure of an Investigator • All research records are retained by the VA facility where the research was conducted • If investigator transfers to another VA facility, the investigator must obtain approval for a copy of relevant materials to be provided to the new VA facility’s research office from • First VA facility’s research office • Any other relevant individuals or offices according to VA & local requirements (e.g., compliance, privacy, or Information Security Officers (ISOs)) • The sponsor 36

37. Maintaining a Master List of Subjects • Maintaining a master list of all subjects • IRB may waive the requirement to maintain a master list if both • Waiver of documentation of informed consent, & • IRB determines that a master list poses a potential risk to the subjects from a breach of confidentiality 37

38. Chief Research & Development Officer(CRADO) Waivers • International Research • Research involving children • Research involving prisoners 38

39. Investigator ResponsibilitiesKey Points • Uphold professional & ethical standards & practices • Adhere to applicable • VA requirements • VHA Handbook 1200.05 • Other Federal requirements • Local SOPs 39

40. QUESTIONS 40