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 Universityzoya.hamilton@tufts.edu

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