1. INVESTIGATOR RESPONSIBILITIES C. Karen Jeans, MSN COACH Project Analyst

2. Investigator Responsibilities: Fact vs. Fiction Objectives: Define “investigator responsibilities” Compare and contrast regulatory descriptions of investigator responsibilities FDA regulations 21 CFR Parts 50, 56, 312 and 812 Common Rule VHA 1200.5

3. What is an Investigator Required to Do as Stated in the Human Research Regulations?

4. Who is an Investigator?

5. Principal Investigator: FDA Regulations An individual who actually conducts a clinical investigation, i.e., under whose immediate direction the test article is administered or dispensed to or used involving, a subject, or, in the event of an investigation conducted by a team of individuals, is the responsible leader of that team. 21 CFR 50.3(d)

6. Principal Investigator: FDA Regulations Twenty-eight (28) references within 21 CFR 50 and 21 CFR 56 Recipient of IRB actions Specific requirements described for investigators to obtain informed consent

7. Principal Investigator: FDA Regulations Investigational Drug and Investigational Device Regulations 173 references in 21 CFR 312 135 references in 21 CFR 812

8. General Principal Investigator Responsibilities for FDA-Regulated Studies Ensure investigation is conducted according to: Signed investigator statement, Investigational plan and applicable regulations, Applicable regulations for protecting the rights, safety, and welfare of subjects under the investigator's care, and Control of drugs and devices under investigation. 21 CFR 312 and 21 CFR 812

9. Specific Principal Investigator Responsibilities for FDA-Regulated Studies IRB review Supervision of subjects Case histories Record retention Reports: safety, progress, and final Financial disclosure 21 CFR 312 and 21 CFR 812

10. Investigator: Common Rule No definition of an investigator Twenty-three (23) references Investigator defined through description of obtaining data from a human subject participating in activities considered to be human research Informed consent requirements

11. Investigator: VHA 1200.5 91 References to Principal Investigator or Investigator 10 Investigator Responsibilities 10 References: Phrase “investigator must”

12. VHA 1200.5: Who is an investigator? Principal Investigator: An individual who conducts a research investigation, i.e. under whose immediate direction research is conducted, or, in the event of an investigation conducted by a team of individuals, is the responsible leader of the team. The FDA considers a PI and an investigator to be synonymous. VHA 1200.5, Paragraph 3(t) Investigator: An individual under the direction of the Principal Investigator who is involved in some or all aspects of the research project. VHA 1200.5, Paragraph 3(n)

13. VHA 1200.5: Ten Responsibilities of Investigators 1.Training 2.Research plan 3.Informed consent and authorization for use and disclosure of subject PHI 4.Delegation of interview for obtaining consent 5.Documentation of informed consent VHA 1200.5, Paragraph 10

14. VHA 1200.5: Ten Responsibilities of Investigators 6.Report Serious Adverse Events and Unexpected Adverse Events 7.Approval of amendments and modifications 8.Obtain initial and continuing IRB review and submit modifications 9.Retain records at VA facility if investigator leaves 10.Provide IRB with information concerning request for waiver or alteration of the HIPAA Authorization VHA 1200.5, Paragraph 10

15. VHA 1200.5: Investigator Responsibilities “Investigator Must” References: 1. Defines who is a VA investigator 2. Submit a progress report for IRB continuing review 3. Make appropriate disclosures to a subject’s surrogate during an informed consent process 4. Have approval from the IRB and R&D Committees for conduct of investigational device studies 5. Demonstrate to IRB compelling reason to include incompetent persons or persons with impaired decision- making capacities as subjects

16. Five Key Areas of Investigator Responsibility Research Plan Informed Consent Adverse Event Reporting Records Drug and Device Accountability

17. Do the Human Research Regulations Include All Areas of Investigator Responsibilities?