INVESTIGATOR RESPONSIBILITIES

C. Karen Jeans, MSNCOACH Project Analyst

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

What is an Investigator Required to Do as Stated in the Human Research

Regulations?

Who is an Investigator?

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)

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

Principal Investigator: FDA Regulations• Investigational Drug and

Investigational Device Regulations• 173 references in 21 CFR 312• 135 references in 21 CFR 812

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

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

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

Investigator: VHA 1200.5 • 91 References to Principal

Investigator or Investigator• 10 Investigator Responsibilities• 10 References: Phrase “investigator

must”

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)

VHA 1200.5: Ten Responsibilities of Investigators1. Training2. Research plan3. Informed consent and authorization

for use and disclosure of subject PHI4. Delegation of interview for obtaining

consent5. Documentation of informed consent

VHA 1200.5, Paragraph

10

VHA 1200.5: Ten Responsibilities of Investigators6. Report Serious Adverse Events and

Unexpected Adverse Events7. Approval of amendments and modifications8. Obtain initial and continuing IRB review and

submit modifications9. Retain records at VA facility if investigator

leaves10.Provide IRB with information concerning

request for waiver or alteration of the HIPAA Authorization

VHA 1200.5, Paragraph 10

VHA 1200.5: Investigator Responsibilities“Investigator Must” References:

1. Defines who is a VA investigator2. Submit a progress report for IRB continuing review 3. Make appropriate disclosures to a subject’s surrogate during an informed consent process4. Have approval from the IRB and R&D Committees for conduct of investigational device studies5. Demonstrate to IRB compelling reason to include

incompetent persons or persons with impaired decision- making capacities as subjects

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

Do the Human Research RegulationsInclude All Areas of

Investigator Responsibilities?