Steps Required To Conduct Research
Involving Human Subjects
APRIL 10, 2012
SERIES 2, SESSION 5 OF AAPLS
JENNIFER GRAF, DIRECTOR,
INSTITUTIONAL REVIEW BOARD (IRB)
APPLICANTS & ADMINISTRATORS
PREAWARD LUNCHEON SERIES
Goals for this Session
Explain what the role of the IRB office.
Discuss what research falls under its purview.
Explain the process of having research approved by
the IRB, including post-approval responsibilities.
Discuss what IRB-related information is needed at
the Just In Time phase of grant application.
Nuremberg Trials: Nuremberg Code (1947)
Tuskegee Syphilis research (1932-1972)
Jesse Gelsinger Ellen Roche (2001)
(1951-early 1970s; book published 2010)
Guatemala Syphilis Experiment
(1946-1948; reported October 2010)
Susan Reverby John C. Cutler, MD
Applying Ethical Principles
• Respect for Persons: Autonomy
• Informed consent
• Voluntary participation
• Freedom to withdraw without penalty
• Protect privacy and confidentiality
• Beneficence: “Do unto others…”
• Risks are minimized; Benefits are maximized
• Risks are justified by potential benefits
• Conflicts of interest are managed or eliminated
• Justice: Distribute Risks and Benefits
• Protection of vulnerable populations
• Those who may benefit are not excluded
IRB Determinations and Types of Review
• Not Human Subject Research
• Initial Review
• Convened IRB
• Continuing Review
• Serious Adverse Events (SAE) and
• Case reports
Note: Students, fellows, etc., cannot be the PI of research at Tufts.
Regulations and Policies
• DHHS: 45 CFR 46
• FDA: 21 CFR 50, 56, 312, 812
• Vary state to state
• MA Fetal Research Statute
• Be familiar with institutional policies
Does Not Constitute Human
• Certain coded or de-identified analyses
• Not to be determined by the Investigator
• Provide a detailed letter of activities to the IRB; a written determination is
returned to the Principal Investigator
• Quality Improvement/Assurance initiatives
• Engaged in research:
* Link to guidance document on IRB website.
• Governed by 45 CFR 46.101(b)
• 6 very specific categories
• Request for Exemption form
• Protocol, any documents given to subjects
• PI’s COI disclosure form, others as indicated
• Copy of the grant, if applicable
• HIPAA documentation
Expedited (minimal risk)
Governed by 45 CFR Education requirements
46.110(b) – 9 specific satisfied
Form I Questionnaires, cover
Protocol letters, surveys, etc.
Copy of the grant, if HIPAA documentation
PI’s COI disclosure form,
others as indicated
Database/Medical Record Review
• Form VII – specifically designed for database and
retrospective medical record review research.
• May be exempt, may be expedited – depends on the data
collected and the intervention (if any) with subjects.
• Form VII is designed to eliminate the need for a separate
protocol, ICF, and HIPAA documentation.
• Best to complete the education requirements prior to
Convened IRB Review
(greater than minimal risk)
• Form I (all studies) Protocol/Site-Specific
• Form II (drug/compound) Appendix
• Form III (device) ICF(s)/parent/guardian
• Form IV (research radiation) permission form/assent
• Form VI form
Optional TB ICF Questionnaire(s), contact
• PI’s COI disclosure form, others letters, surveys, etc.
as indicated Education requirements
Copy of the grant, if
Special Populations: Contact the IRB
office for guidance when preparing
•P r e g n a n t w o m e n
•N e o n a t e s o r f e t u s e s
•M i n o r s
•D e c i s i o n a l l y i m p a i r e d
•P r i s o n e r s
•E m p l o y e e s o r s t a f f
•S t u d e n t s
Phases of Clinical Research Studies
• metabolic & pharmacologic mechanisms; determine a safe dosage range;
small group of people (e.g., 20-80); identify side effects.
• Pose a high level of risk due to “initial introduction” of the test article
into a human; little or no prior human experience.
• controlled; preliminary effectiveness in subjects with the disease of
interest; several hundred subjects; determine efficacy and further
evaluate safety. Pose a high level of risk due to limited human
• controlled & uncontrolled; increased human exposure to the test article
(several hundred to several thousand); seek safety & effectiveness data
for extrapolation to a larger population; monitor adverse effects.
• conducted after intervention is marketed; long-term safety and efficacy
data acquisition in a larger population; information about any Adverse
Events associated with widespread use.
PI Post-Approval Responsibilities
• Report serious
• Continuing Review
• Submit requests to
change or amend the
research for review
and approval prior to
Expedited and Exempt
Reviewed by IRB Chair or Vice-Chair
Clarification requested. PI submits
Approval letter generated, signed and sent to the PI.
IRB members notified.
Assigned to an IRB agenda
Assigned a Primary and Secondary Reviewer
Reviewed at a convened IRB meeting
IRB comment letter sent to PI
within 2 weeks of the meeting
Principal Investigator responds to IRB review
stipulations/requests for clarification:
Submission is reviewed by “expedited review procedures.
If necessary, additional information, etc.,
is requested from the PI.
Approval letter is generated, signed, and sent to the PI.
IRB members are notified.
Helpful Tips For Submission Preparation
• Ensure the protocol details all procedures.
• Ensure the ICF is in simple language (8th grade reading level)
• Proof read! And make sure all documents are present and required signatures
• Review information on the IRB website, use templates
• If applicable, provide a copy of the grant
• Provide requisite supporting documentation.
• Provide tracked and untracked copies of revised documents; always include a
version date or number on all documents.
• Ensure education requirements are satisfied; retain copies of certificates of
completion (subject to audit!)
• COI form(s) complete and submitted, as needed.
The Best Advise for a Quick and
Successful IRB Review…
• Review IRB website, get familiar with issues.
• Discuss the project with other research-experienced faculty,
develop a plan (and a protocol).
• Call the IRB office – schedule an appointment to meet with a
member of the office.
• Speak with an IRB member.
IRB Chair: Andreas K. Klein, MD
IRB Vice-Chairs: Susan Hadley, MD
Gordon Huggins, MD
Roman Schumann, MD
IRB Members are from more than 20 different divisions at
Tufts MC and Tufts University, including TUSM, TUSDM,
HNRCA, etc., non-scientists, and community representatives
who are not affiliated with either institution.
•Director, IRB Operations: Jennifer A. Graf
• IRB Coordinators: Julie Morelli Novak (Red)
Ashley D. Hicks (Blue)
• Continuing Review Coordinators: Christine Choy (Blue)
Andrew L. Simon (Red)
• Assistant IRB Coordinator: Jesslyn Jamison
• Administrative Assistants: Robert J. Santoro (PT)
15 Kneeland Street, 1st floor
Zoya Hamilton, CRA, EdD
Sr. Associate Director
Office of the Vice Provost
Externally-Funded Projects with Human Subjects
Sponsor agency requires confirmation that the
project funded by the award is approved by Tufts
This confirmation is necessary before the release of
the funds by the agency (Just In Time – JIT)
If award is pass-through, the prime recipient
requests a copy of the IRB approval letter with
Communicating IRB Approval to Sponsor
Your Signing Official (SO) from the Office of Research
Administration (ORA) will confirm the IRB approval to
SO will determine whether or not the sponsor requires a
copy of the IRB letter or just the IRB approval date
NIH typically only requires the approval date unless the
IRB letter is specifically requested
ORA requires a copy of the IRB approval letter in order
to communicate the IRB approval to sponsor
It is PI’s responsibility to provide a copy of the IRB
approval to ORA
Just In Time
JIT information is an administrative piece that is
necessary for the release of funds
In most cases when JIT is requested via personal
email funding will be awarded
JIT link in Commons is not an indicator of funding
Occasionally (most often before the federal fiscal
year end) award may be issued with a restriction on
the use of human subjects when the IRB approval is
not in place