Document Sample
Research_Involving_Human_Subjects-Session5 Powered By Docstoc
					Steps Required To Conduct Research
     Involving Human Subjects

            APRIL 10, 2012

               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              Ellen Roche (2001)

                  2001 VCU
             Henrietta Lacks
(1951-early 1970s; book published 2010)

                                 Guatemala Syphilis Experiment
                               (1946-1948; reported October 2010)

                            Susan Reverby        John C. Cutler, MD
                           Wellesley College
          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 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
• State:
   • Vary state to state
   • MA Fetal Research Statute
• Be familiar with institutional policies
                  Does Not Constitute Human
                       Subject Research*
• 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.
                       (minimal risk)
•   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
    categories                   Advertisement(s)
   Form I                       Questionnaires, cover
   Protocol                      letters, surveys, etc.
   Copy of the grant, if        HIPAA documentation
   ICF(s)
   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
   Tissue-banking                      Advertisement(s)
   Optional TB ICF                     Questionnaire(s), contact
• PI’s COI disclosure form, others       letters, surveys, etc.
  as indicated                          Education requirements
                                        HIPAA documentation
                                        Copy of the grant, if
Special Populations: Contact the IRB
  office for guidance when preparing
       protocol/IRB application

 •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
 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
 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.
PI Post-Approval Responsibilities
                 • 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.
          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.
       Convened IRB
        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
    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…

• 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 Office
         Box 817
      (617) 636-7512
15 Kneeland Street, 1st floor

Zoya Hamilton, CRA, EdD
  Sr. Associate Director
Research Administration
Office of the Vice Provost
     Tufts University
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
  subcontract paperwork
    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

Shared By: