Definitions of Human Subjects Research by ewghwehws

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									Office of Research Integrity and Compliance

 Institutional Review
    Board Basics
          July 18, 2007



                    Annie Munana, Director ORIC
                    Ellen Brooks, PhD, IRB Chair
                      April Baker, IRB Manager
                     Johari Harris, IRB Specialist
                     Patty Zavalza, IRB Specialist
                  Carmen Wheeler, Sr. Admin. Assist.
Office of Research Integrity and
          Compliance



   Pre-Award                Post-Award




               Compliance
         Key Definitions of Human
             Subjects Research
   RESEARCH - A systematic investigation designed to
    develop or contribute to generalizable knowledge.


   CLINICAL TRIAL - A controlled study involving
    human subjects, designed to evaluate prospectively the
    safety and effectiveness of new drugs or devices or of
    behavioral interventions.
      Key Definitions of Human Subjects
               Research, cont’d
   HUMAN SUBJECTS – Individuals whose physiologic or
    behavioral characteristics and responses are the object of study
    in a research project…living individual(s) about whom an
    investigator conducting research obtains: (1) data through
    intervention or interaction with the individual; or (2) identifiable
    private information
   INFORMED CONSENT – Is a human subject’s voluntary
    agreement, based upon adequate knowledge and understanding
    of relevant information, to participate in research or to undergo
    a diagnostic, therapeutic, or preventive procedure.
          Ethical Principles for Human Subjects:

           [The Belmont Report, April 18, 1979]

   RESPECT FOR PERSONS - that individual autonomy be
    respected and that persons with diminished autonomy be protected.


   BENEFICENCE - the obligation to protect persons from harm: (1) do
    not harm; and (2) protect from harm by maximizing possible benefits and
    minimizing possible risks of harm.


   JUSTICE - requires fairness in distribution of burdens and benefits; often
    expressed in terms of treating persons of similar circumstances or
    characteristics similarly.
       Institutional Review Boards
                  (IRBs)
IRB – a review body established or designated by an entity to protect the
    welfare of human subjects recruited to participate in biomedical or
    behavioral research

RESPONSIBILITIES –
   Apply Code of Federal Regulations (CFR) and Good Clinical Practice (GCP)
    standards for Human Subjects Research
   Review and Approve
   Require Modification in
   Disapprove
…ALL research activities, including proposed changes in
    previously approved human subject research
     IRB Responsibilities, cont’d


   Has the authority to SUSPEND or
    TERMINATE previously approved research
    that is NOT being conducted in accordance
    with the IRB’s requirements or under CFR and
    GCP standards, or that has been associated
    with unexpected serious harm to subjects
             Principal Investigator
                Responsibilities
1.   Comply with Human Subjects Education
     Requirement for themselves as well as key personnel

2.   Design and Implement Ethical Research Studies

3.   Comply with Code of Federal Regulations and Good
     Clinical Practice Standards

4.   Obtain prior IRB Approval

5.   Comply with IRB/HIPAA Requirements
             Principal Investigator
            Responsibilities, cont’d
6.    Implement Research as Approved and Obtain Prior
      Approval for Modifications

7.    Obtain Informed Consent/Assent/Authorizations

8.    Document Informed
      Consent/Assent/Authorizations

9.    Submit Progress Reports

10.   Report Unanticipated Problems

11.   Retain Records and Document Activities
                            What is HIPAA?
The Law: Health Insurance Portability and Accountability Act
of 1996 (HIPAA)

The Resulting Regulations: HHS issued regulations entitled Standards for Privacy
    of Individually Identifiable Health Information, known as the Privacy Rule, compliance
    required by April 14, 2003

  Establishes privacy standards to protect a person’s health
Information
 Impact: Regulations impact how both researchers and IRB
conduct their research and duties
http://privacyruleandresearch.nih.gov/privacy_boards_HIPAA_privacy_rule.asp
        Types of Submissions

        – New Studies
 Initial
 Continuing/Annual Review
 Amendments and Revisions
 Adverse Events
 Emergent Requests (Medical)
 Final Report/Inactivations
            Risk Determinations under Subpart D

Protocol are approved under the following risk/benefit
  determination:
   Research not involving greater than minimal risk. (45 CFR §46.404)
   Research involving greater than minimal risk but presenting the
    prospects of direct benefit to the individual subjects. (45 CFR §46.405)
   Research involving greater than minimal risk and no prospect of
    direct benefit to individual subjects but likely to yield generalizable
    knowledge about the subject’s disorder or condition. (45 CFR §46.406)
   Research not otherwise approvable which presents an opportunity
    to understand, prevent or alleviate a serious problem affecting the
    health or welfare of children. (45 CFR §46.407)
       Informed consent

 Process
 Documentation
 Alterations   and Waivers
                    Informed Consent

   Subjects reaching the age of majority (18 years of age) must re-
    consent to continue participating in research if they were initially
    enrolled to the study by their parent/guardian when they were
    minors.
   IRB is finalizing revisions to the consent template and a short
    form that will be used for re-consenting adult patients.
   Also will provide a list of common medical terms and the
    suggested “lay language” descriptions.
        HHS Requirements for Waiving
             Informed Consent
 IRB must approve and document findings
 When Permitted:
     Research is no more than minimal risk
     The rights and welfare of subject are not adversely
      affected
     Research could not be practicably conducted
      without the waiver
     Subjects provided with pertinent information after
      participation
                  Wards of the State

   Any participation of Wards of the State in research studies
    regardless of the risk determination must have the prior
    approval of the Department of Children and Family Services
    (DCFS). Any research conducted under 46.406 or 46.407 must
    also utilize a Research Subject Advocate for each ward to be
    enrolled. Please contact the IRB for guidance prior to
    enrolling Wards of the State on any research study
    regardless of the assigned risk determination. The IRB
    Chair, is the designated Research Subject Advocate for
    CMH. If the Chair is the PI for the study, the IRB will
    appoint an alternate as appropriate.
           Types of Review

 Exempt
 Expedited
   Minimal   Risk
 Full   Committee Review
   Minimal  Risk
   Greater than Minimal Risk
Types of Research Eligible
  for “Exempt” Review
   Six Categories – special added considerations for
    children
   Determination made locally to accept categories
   Research must fall into one or more of the
    categories to be exempt
   PI cannot make determination. Qualified
    individual makes this determination
   May still require consent or other safeguards
   Any changes require IRB re-review
            Mechanism of Review:
            “Expedited” Research
 Review carried out by IRB chair or by one or more
  experienced reviewers
 Reviewers may approve or modify, but may not
  disapprove
 Rigor of review the same as for full IRB review;
  number or reviewers different
 Expedited does not necessarily mean a fast review
        Continuing/Annual Review

   PI’s are responsible for monitoring the approvals for
    their studies.
   Must be done no less than annually for ongoing studies
   More frequent review may be necessary for some
    research studies
   IRB sends out progress report forms approx. 2-3
    months prior to the studies expiration date
   2 opportunities for submission are given
      Amendments and Revisions

 Require approval before implemented (unless to
  eliminate safety issue)
 Evaluate impact of change risk/benefit
  assessment
 “Minor” changes may undergo expedited review
                   Adverse Events
   Serious adverse events or unanticipated events that
    involve risks to others must be reported to the IRB in a
    timely manner
   Researcher must provide interpretation of events and
    description of precautions taken to prevent reoccurrence.
    You must provide a copy of the current consent form for
    review.
   Review of events should be commensurate with severity
   IRB has new SAE Submission Policy
               Emergency Requests
   Patient requires emergent research treatment in the event of life
    threatening situation.
      No approved IRB Protocol
      No time for IRB review

   HHS: Regulations do not prevent MD from administering treatment in
    an emergent situation: Do not consider it prospective research

   FDA: Has procedures report to FDA and IRB within 5 days, allows
    informed consent waiver

   www.fda.gov/oc/ohrt/irbs/drugsbiologics.html#emergency

   Intended to be used only once
           Final Report/Inactivations

   Studies may be closed once all research activities have been
    completed including data analysis
   If the study is part of a large multi-center trial, the study may be
    inactivated once all enrolled subjects have completed all
    research interventions and data is no longer being submitted to
    the sponsor
   Inactivations may be requested at the time of the continuing
    review or may be submitted at any time during the year of
    approval
   IRB strongly encourages the submission of a final report rather
    than allowing the study to expire
        Types of Approval

   Approved without Contingencies

   Approved with Contingencies

    - minor directed

    - major

   Tabled

   Disapproved/Rejected
                  Approved without
                   Contingencies
   No revision is necessary to any submitted document
   Provided all administrative contingencies are met, the
    approval paperwork can be released
         Approved with Minor Directed
                Contingencies
   Requires clarification of an aspect of the study or revision to
    one or several documents
   May or may not have to be reviewed by the convened IRB
        Directed changes (e.g. editorial changes in wording)
        Non-Directed clarifications or disagreements with the proposed directed
         changes may have to be reviewed by the IRB
        Any contingencies must be resolved before the 4-month contingency
         period expires or full resubmission of the study is required
           Approved with Major
             Contingencies

 Changes are not directed
 Eligible for major contingency conference call
 Response must be complete and submitted by
  the deadline.
 Conference calls occur outside of regular
  meetings
                         Tabled

   Usually major issues with the protocol or consent
    documents
   Requires resubmission of the entire proposal with a
    point by point response to each question
   Resubmission may occur at any time – no contingent
    approval period
   IRB deadlines must be met for inclusion on the next
    meeting’s agenda
         Disapproved/Rejected

 Similar to Tabled but sends a stronger message
 May be appealed
 Resubmission of study is necessary
 May be resubmitted at any time – no contingent
  period
                        IRB Statistics
   Oversees approximately 800 active studies

          2007          April      May          June
     Total
     submissions       254         214          207
     reviewed

   The majority of submission reviews require some degree of
    follow-up and require correspondence to be generated by
    the IRB staff – including stamping consents
                                                          31
       New Policies for 2007

 SAE Submissions
 Complete Submissions
 Major Contingencies Conference Call
                   SAE Submissions

   Hard copy submissions only
         - Cover memo must be signed by PI
   External Events – Non CMH Patients
         - Only events for studies being conducted at CMH
         - Meets the “3-question” test
   Internal Events – CMH Patients
         - Only serious events
   For all submissions, include 1 copy of current consent
         Complete Submissions

 Only complete submissions will be forwarded
  for review
 Incomplete submissions will be returned and
  PI/CRA notified
 Checklist available on IRB website
        Elements of Complete Initial IRB
             Protocol Submission
   Office of Sponsored Programs (OSP)
    Proposal/Protocol Routing Form (1 signed original
    form and 3 copies)

   Budget (if applicable)

   Support Letter(s) (if applicable)

   Research Plan (5-7 pages maximum lay-language
    summary)

   Full Protocol (if applicable, primarily cooperative group
    and industry-sponsored studies)
        Elements of Complete Initial IRB
           Protocol Submission, cont’d
   Parental Consent Form(s) (for children <18 years of age)

   Assent Form(s) (if children 12-17 years of age)

   Adult Subject Consent Form(s) (Individuals >18 years of age)

   Any other study-related materials (e.g. surveys, questionnaires,
    Investigator Brochure if an investigational drug study or
    Manufacturer Package Insert if investigational device study,
    advertisements, etc.)
       Elements of Complete Initial IRB
         Protocol Submission, cont’d
   Current Human Subject’s Education certification
    for all listed study personnel
   Electronic copies of OSP form,
    protocol, advertisements, surveys, other
    documents should also be sent via email to the
    IRB email address: irb@childrensmemorial.org
            Major Contingencies
             Conference Call
 Approx. 2 weeks to respond to contingencies
 Only complete responses are eligible for the
  conference call
 Responses not received by deadline will be
  reviewed at the next convened IRB meeting
 Schedule for conference calls is available on the
  IRB website
Questions and Answers

								
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