APRIL 10, 2012
SERIES 2, SESSION 5 OF AAPLS
JENNIFER GRAF, DIRECTOR,INSTITUTIONAL REVIEW BOARD (IRB)
APPLICANTS & ADMINISTRATORS PREAWARD LUNCHEON SERIES
Steps Required To Conduct Research
Involving Human Subjects
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)
Thalidomide (1962)
Jesse Gelsinger (2000)
Ellen Roche (2001)
2001 VCU
Henrietta Lacks(1951-early 1970s; book published
2010)
Susan ReverbyWellesley College
John C. Cutler, MD
Guatemala Syphilis Experiment (1946-1948; reported October 2010)
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
• Exempt• Expedited• Convened IRB
• Continuing Review• Amendment/Revision• Serious Adverse Events (SAE) and
Unanticipated Problems• Other
• Case reportsNote: Students, fellows, etc., cannot be the PI of research at Tufts.
• Be familiar with institutional policies
Regulations and Policies
• DHHS: 45 CFR 46• FDA: 21 CFR 50, 56, 312, 812• State:
• Vary state to state• MA Fetal Research Statute
Does Not Constitute Human Subject Research*
• Certain coded or de-identified analyses
• http://www.hhs.gov/ohrp/policy/cdebiol.html
• 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:
http://www.hhs.gov/ohrp/policy/engage08.html
* 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
Exempt (minimal risk)
Expedited (minimal risk)Governed by 45 CFR
46.110(b) – 9 specific categories
Form IProtocolCopy of the grant, if
applicableICF(s)PI’s COI disclosure form,
others as indicated
Education requirements satisfied
Advertisement(s)Questionnaires, cover
letters, surveys, etc.HIPAA documentation
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 submission.
Convened IRB Review(greater than minimal risk)
• Form I (all studies)• Form II (drug/compound)• Form III (device) • Form IV (research radiation)• Form VI
Tissue-banking Optional TB ICF
• PI’s COI disclosure form, others as indicated
Protocol/Site-Specific Appendix
ICF(s)/parent/guardian permission form/assent form
Advertisement(s)Questionnaire(s),
contact letters, surveys, etc.
Education requirementsHIPAA documentationCopy of the grant, if
applicable
•Pregnant women•Neonates or fetuses•Minors•Decisionally impaired•Prisoners•Employees or staff•Students
Special Populations: Contact the IRB office for guidance when preparing
protocol/IRB application
Phases of Clinical Research Studies
Phase I:• 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.
Phase II: • 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 experience.
Phase III:• 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.
Phase IV: • 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.
• Report serious adverse events
• Report unanticipated events• Continuing Review
• Submit requests to change or amend the research for review and approval prior to initiating changes.
PI Post-Approval Responsibilities
Expedited and Exempt
Reviewed by IRB Chair or Vice-Chair
Clarification requested. PI submits additional information.
Approval letter generated, signed and sent to the PI. IRB members notified.
Reviewed at a convened IRB meeting
Convened IRB
Assigned to an IRB agendaAssigned a Primary and Secondary Reviewer
IRB comment letter sent to PIwithin 2 weeks of the meeting
Approval letter is generated, signed, and sent to the PI.IRB members are notified.
Principal Investigator responds to IRB reviewstipulations/requests for clarification:
Submission is reviewed by “expedited review procedures.
If necessary, additional information, etc., is requested from the PI.
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 are present.
• 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…
PLAN IN
ADVANCE
•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 Leadership
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.
IRB office
•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)
TBA (FT)
IRB OfficeBox 817
(617) 636-751215 Kneeland Street, 1st floor
http://tnemcirb.tufts.edu/
Presenter
Zoya Hamilton, CRA, EdDSr. Associate Director
Research AdministrationOffice of the Vice Provost
Tufts [email protected]
Externally-Funded Projects with Human Subjects
Sponsor agency requires confirmation that the project funded by the award is approved by Tufts IRB
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 subcontract paperwork
Communicating IRB Approval to Sponsor
Your Signing Official (SO) from the Office of Research Administration (ORA) will confirm the IRB approval to sponsor
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 decision
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