SoCRA Review: Investigator Roles
and Responsibilities in Clinical
Research
John Naim, PhD
Director
Clinical Trials Research Unit
West Virginia University
March 20, 2015
Outline
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Historical Perspective
Legal Framework
Clinical Investigator
Roles and Responsibilities
GCP Q & A
Discussion
West Virginia Clinical and Translational Science Institute
Disclaimer
Information from: FDA Clinical Investigator Training Course
http://www.fda.gov/downloads/Training/ClinicalInvestigatorTrainingCourse/UCM378565.pdf
GCP questions from Paul Below presentation:
http://www.slideshare.net/PaulBelow/so-you-think-you-know-gcp-mar-2013
West Virginia Clinical and Translational Science Institute
Historical Perspective
Past transgressions lead to the need for laws that
protect the rights and welfare of human subjects.
• Nuremberg Doctors Trial of 1946 (Nuremberg
Code)
• Thalidomide Tragedy (Kefauver-Harris Amendment)
• Tuskegee Experiments (Belmont Report)
• Human Radiation Experiments
• Gene Transfer Experiment
West Virginia Clinical and Translational Science Institute
Historical Perspective
Past transgressions lead to the need for laws that
protect the rights and welfare of human subjects.
• Nuremberg Doctors Trial of 1946 (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
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
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
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
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
Commitments on Form 1572
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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 312.64)
Maintain adequate and accurate records and make them available
for inspection in accordance with 21 CFR 312.68
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
Frequently Asked Questions Form 1572
Why does this form need to be completed
by an investigator?
West Virginia Clinical and Translational Science Institute
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
Frequently Asked Questions Form 1572
Does the 1572 need to be submitted to
FDA?
West Virginia Clinical and Translational Science Institute
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
Frequently Asked Questions Form 1572
Are CVs required to be signed and dated?
West Virginia Clinical and Translational Science Institute
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
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
West Virginia Clinical and Translational Science Institute
Investigator Responsibilities (cont.)
Investigator reports (312.64)
 Progress reports
 Safety reports
o 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)
o Immediately report any adverse event that is
alarming (e.g. an unexpected event that is serious or
life‐threatening)
Final report
Financial disclosure
West Virginia Clinical and Translational Science Institute
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)
West Virginia Clinical and Translational Science Institute
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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Ready for some GCP Questions?
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West Virginia Clinical and Translational Science Institute
West Virginia Clinical and Translational Science Institute
West Virginia Clinical and Translational Science Institute
West Virginia Clinical and Translational Science Institute
West Virginia Clinical and Translational Science Institute
West Virginia Clinical and Translational Science Institute
West Virginia Clinical and Translational Science Institute
West Virginia Clinical and Translational Science Institute
West Virginia Clinical and Translational Science Institute
West Virginia Clinical and Translational Science Institute
West Virginia Clinical and Translational Science Institute
West Virginia Clinical and Translational Science Institute
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www.wvctsi.org
Questions?
Thank You
Made possible by IDeA CTR support –
NIH/NIGMS Award Number U54GM104942
West Virginia Clinical and Translational Science Institute