1. SoCRA Review: Investigator Roles and Responsibilities in Clinical Research
John Naim, PhD
Director
Clinical Trials Research Unit
West Virginia University
March 20, 2015

2. Outline Historical Perspective Legal Framework Clinical Investigator
Roles and Responsibilities
GCP Q & A
Discussion
West Virginia Clinical and Translational Science Institute

3. Disclaimer Information from: FDA Clinical Investigator Training Course
GCP questions from Paul Below presentation:
West Virginia Clinical and Translational Science Institute

4. Historical Perspective
Past transgressions lead to the need for laws that protect the rights and welfare of human subjects.
Nuremberg Doctors Trial of (Nuremberg Code)
Thalidomide Tragedy (Kefauver-Harris Amendment)
Tuskegee Experiments (Belmont Report)
Human Radiation Experiments
Gene Transfer Experiment
West Virginia Clinical and Translational Science Institute

5. Historical Perspective
Past transgressions lead to the need for laws that protect the rights and welfare of human subjects.
Nuremberg Doctors Trial of (Nuremberg Code)
Thalidomide Tragedy (Kefauver-Harris Amendment)
Tuskegee Experiments (Belmont Report)
Human Radiation Experiments
Gene Transfer Experiment
The public trust is sine qua non of clinical research
West Virginia Clinical and Translational Science Institute

6. Legal Framework Federal Food, Drug, and Cosmetic Act (FD&C Act)
Section 505(i) is the statutory authority for FDA’s oversight of clinical investigations to test safety and effectiveness
Code of Federal Regulations (CFR)
Regulations promulgated under Section 505(i) describing FDA’s authority over the conduct of clinical investigations including
-Sponsor Responsibilities
-Clinical Investigator Responsibilities
Guidance – advisory only, to assist clinical investigators and sponsors in complying with the regulations
FDA Form 1572 – by signing this form, an investigator agrees to conduct a study in accordance with the protocol and applicable regulations and to provide adequate supervision of a study
West Virginia Clinical and Translational Science Institute

7. Legal Framework (cont.)
Good Clinical Practice (GCP): A standard for the design, conduct, performance, monitoring, auditing, recording, analyses, and reporting of clinical trials that provides assurance that the data and reported results are credible and accurate, and that the rights, integrity, and confidentiality of trial subjects are protected.
West Virginia Clinical and Translational Science Institute

8. The Clinical Investigator
An individual who actually conducts a study (i.e. under whose immediate direction the drug is dispensed to a subject.)
In the event an investigation is conducted by a team of individuals, the investigator is the responsible leader of the team.
[21 CFR 312.3]
West Virginia Clinical and Translational Science Institute

9. Investigator Roles
Good Clinical Practice (GCP) in FDA‐regulated research is not the same as good clinical practice in caring for patients
For example, FDA regulations have very specific requirements for following the protocol, recordkeeping, and drug accountability
Regulations are designed to:
-Ensure the quality and integrity of data collected in clinical trials
-Ensure that the rights, safety and welfare of research participants
are protected
West Virginia Clinical and Translational Science Institute

10. Commitments on Form 1572 Personally conduct or supervise investigation
Follow protocol
Ensure all persons assisting is study are informed of obligations
Inform subjects that drugs are being used for investigational purposes
Ensure informed consent (21 CFR Part 50) and IRB review, approval and reporting (21 CFR Part 56)
Report to sponsor adverse events (21 CFR )
Maintain adequate and accurate records and make them available for inspection in accordance with 21 CFR
Ensure initial and continuing review by an IRB and report all changes to research and unanticipated problems involving risks to subjects, not make any changes without IRB approval except where necessary to eliminate immediate hazards
Comply with other requirements in 21 CFR 312
West Virginia Clinical and Translational Science Institute

11. Frequently Asked Questions Form 1572
Why does this form need to be completed by an investigator?
West Virginia Clinical and Translational Science Institute

12. Frequently Asked Questions Form 1572
Why does this form need to be completed by an investigator?
1) To provide the sponsor with information about the investigator’s qualifications and clinical site. 2) To inform the investigator of his/her obligations and obtain the investigator’s commitment to follow pertinent FDA regulations. Making willfully false statement is a criminal offense.
West Virginia Clinical and Translational Science Institute

13. Frequently Asked Questions Form 1572
Does the 1572 need to be submitted to FDA?
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14. Frequently Asked Questions Form 1572
Does the 1572 need to be submitted to FDA?
No. Although the sponsor is required to collect 1572 from the investigator, FDA does not require the form to be submitted to the agency.
West Virginia Clinical and Translational Science Institute

15. Frequently Asked Questions Form 1572
Are CVs required to be signed and dated?
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16. Frequently Asked Questions Form 1572
Are CVs required to be signed and dated?
No. FDA regulations do not require a CV to be signed and dated. The investigator’s dated signature on the 1572 is sufficient to attest to the accuracy of the CV or other statement of qualifications submitted.
West Virginia Clinical and Translational Science Institute

17. Investigator Responsibilities
General responsibilities (312.60)
Control of investigational drug (312.61)
Record keeping and retention (312.62)
Maintaining adequate records of the disposition of the drug
Accurate case histories that record all observations, and
Other data pertinent to the investigation on each individual administered the investigational drug or employed as a control in the investigation
An investigator is required to maintain investigation records for:
2 years following the data a marketing application is approved for the drug for the indication for which it is being investigated
2 years after the investigation is discontinued and FDA is notified if no application is to be filed or if the application has not approved for such indication
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18. Investigator Responsibilities (cont.)
Investigator reports (312.64)
Progress reports
Safety reports
Promptly report any adverse event that may reasonably be regarded as caused by, or probably caused by, the drug (err on the side of reporting)
Immediately report any adverse event that is alarming (e.g. an unexpected event that is serious or life‐threatening)
Final report
Financial disclosure
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19. FDA Guidance Investigator Responsibilities
Outlines FDA expectations for study oversight Appropriate delegation of study tasks
Appropriate training of study staff
Appropriate supervision of conduct of ongoing study
Appropriate oversight of third parties involved in the study (e.g. Site Management Organizations, outside labs specifically retained to conduct study assessments)
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20. FDA Guidance Investigator Responsibilities (Cont.)
Outlines FDA expectations for protecting the rights, safety, and welfare of subjects
Provision of reasonable medical care for issues related to study participation (e.g.to manage an adverse event)
Facilitation of care for other health issues that might arise during the study
Avoiding exposure of subjects to unreasonable risks
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21. Ready for some GCP Questions?
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35. Questions? Thank You www.wvctsi.org
Made possible by IDeA CTR support –
NIH/NIGMS Award Number U54GM104942
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