Institutional Review Boards (IRBs) and Human Subjects Research by gqz16570


									Institutional Review Boards
         (IRBs) and
 Human Subjects Research
    Protection Programs
       A short course

 Lifespan                     1
Course Content

  Part 1: Brief Description of the IRB
          and Research at Lifespan
  Part 2: IRB Support Staff Function
  Part 3: Researcher Responsibilities
  Part 4: How to submit items for
          review by the IRB
  Part 5: Brief discussion about
          Informed Consent
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           Part 1

  Brief overview of the IRB
  and Research at Lifespan

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               What is an IRB?
    IRB = Institutional Review Board
      • at least 5 members
      • at least 1 must have a scientific background
      • at least 1 must be a non-scientist (this
        member must attend a meeting to achieve
      • at least 1 non-affiliated member (not affiliated
        with the institution)
      • Members should have expertise in the
        research that will be reviewed.

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    IRBs are regulated by State and
          Federal Regulations
   Federal:
    • FDA (Food and Drug Administration,
      Title 21 CFR ) and
    • OHRP (Office for Human Research
      Protection, Title 45 CFR Part 46)
   State of Rhode Island:
       Section 16, Rules and Regulations for
       Licensing Hospitals.

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 Why is research so heavily regulated?
The history of Research has not always
  been one of ethics and regulations –
  Nazi war crimes; Tuskegee syphilis
  study; Yale Milgram experiments
  (obedience to authority, 1961-62); tea
  room experiments (homosexual
  behavior in public restroom – mid

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             The Modern IRB is Born
1974- National Research Act mandated specific
  requirements for institutional review committees
  which became known as Institutional Review
  Boards (IRBs)
1979- The Belmont Report provided guidance as to
  how the new rules should be applied. The Belmont
  Report defined the three philosophical principles
  relevant to research:
      Respect to persons – must provide adequate
        information and obtain voluntary consent
      Beneficence – Minimize harm maximize
      Justice – Selection of subjects must be fair
        and justified
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The Primary Concern of the
   IRB is the Rights and
  Welfare of the Research

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The Main Purpose of IRB Review

   To assess the risk/benefit ratio.
   To ensure that informed consent is
    obtained in an appropriate manner
   To verify that the recruitment
    methods/materials are not misleading or
   To ensure that the selection of subject is
    equitable and justified

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       Research at Lifespan
Lifespan has three IRBs (2 at RIH and 1 at TMH)
   Researchers at Lifespan may submit to any of
   the 3 IRBs. The exception is prison protocols
   which must be submitted to TMH IRB.

The Lifespan Research Program is considered to be
of medium size when compared across the country.
Currently we have:
    1,250 active protocols;
    TMH has 335 and the RIH IRBs have 915

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Lifespan’s HRPP hierarchy
   Dr. Arthur Klein, Sr.VP–
    Institutional Official
       oversight responsibilities for the HRPP,
       delegated to Dr. Klein through the Presidents
       at each Lifespan Affiliate

   Peg McGill -Director
    Lifespan Office of Research Administration
   Pat Houser- Manager
    Research Review Committees

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       Who are the members of
          Lifespan’s IRBs?
Lifespan’s IRBs are made up of physicians,
PhDs, pharmacists, nurses, clergy, retirees,
and community members who VOLUNTEER
their time to review human subject research

Members typically spend 2 hours per month
reviewing protocols and 2+ hours at the IRB
meeting. Chairpersons spend considerably
more time in service to the IRB.

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    Accreditation of the Human
    Research Protection Program
   Lifespan is seeking accreditation of our
    human research protection program
   This accreditation seeks to accredit the
    entire human research protection
    program for all of Lifespan not just the
    IRBs. That means we’re all in this

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           Part 2

Research Review Committee

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                      Who Are We?
The Research Review Committee Office is made up of the following:
IRB Manager-
   Responsible for the management of research activity and IRB support staff
    involved in the daily activities of processing research.
   Assures regulatory compliance of IRB’s as well as researchers and protocols
   Assists the research community with information needed to ensure compliance

Committee Assistants-
   Provide administrative support to the IRB, researchers and coordinators.
   Process, maintain, and update the database, paperwork and files of all research

Committee Coordinators-
   Review initial IRB applications, continuing review, adverse events and
   Act as a communication liaison between the committees and the Investigator
   Review all submissions to the IRB for appropriate documentation
   Transcribes the IRB meeting minutes and follows up with the investigator with
    IRB requests for approval.

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                What Do We Do?
   Review all submissions for completeness and
   Make a preliminary determination of whether the
    submission qualifies for exempt, expedited, or full
    board review
   Process new applications, revisions to current
    protocols, adverse events, continuing reviews, and
    protocol deviations/exception reports
   Prepare the agenda and distribute review materials to
    IRB members
   Prepare meeting minutes and communicate with
    researchers as to what the IRB requires
   Serve as resource to the research community
   Maintain the database

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           Part 3

Researcher Responsibilities

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Responsibility of the PI

    Is to know and understand the
     regulations and policies prior to
     initiating any human research.
    Acknowledge and accept their role
     to protect the rights and welfare of
     the research subjects by complying
     with all of the regulations.

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            GCP and the PI
When a principal investigator receives an approval
  letter from the Lifespan IRB, they are notified
  that this institution and the investigator
  complies with ICH GCP guidelines as they
  correspond to the FDA/DHHS regulations.
Good Clinical Practice (GCP) is an international
  ethical and scientific quality standard for
  designing, conduction, recording and reporting
  trials that involve the participation of human
Compliance with GCP standards provides public
  assurance that the rights, safety and well being
  of trial subjects are being protected and that
  clinical trial data is credible.

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              GCP and the PI
The investigator’s responsibility according to ICH GCP
        4.1 Investigator qualifications and agreements
        4.2 Adequate resources
        4.3 Medical care of trial subjects
        4.4 Communication with IRB
        4.5 Compliance with the protocol
        4.6 Investigational product
        4.7 Randomization procedures and unblinding
        4.8 Informed consent of trial subjects
        4.9 Records and reports
        4.10 Progress reports
        4.11 Safety reporting
        4.12 Premature termination or suspension of a trial
        4.13 Final report by the investigator

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So what are some of the other PI
   Ensure that research activities are carried out according
    to the IRB approved protocol
   Protect subject confidentiality by storing electronic
    research data on password protected computers, and
    paper data in locked cabinets within locked offices
   Follow HIPAA regulations when the research involves the
    use or disclosure of PHI -obtain authorization from
    prospective subjects.
   Ensure that only IRB approved recruitment materials and
    research authorizations are used
   Provide signed copies of consent and authorization forms
    to research subjects and keep the originals in secured
    research files
   When appropriate, place copy of the consent form and
    authorization in the subject’s medical record.

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       So what are some of the other
           requirements for PIs?
    Human Subject Protection (HSP) Training is
     required for all research personnel who interact
     with human subjects or their identifiable data.
     Re-certification is required every 3 years.
    Each PI must also sign a HIPAA Security
     Assurance annually.
    HIPAA for Research training is an annual
     requirement. Each department in Lifespan
     must provide this training to their employees.
    HSP and HIPAA training can be done on-line at

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            Part 4

Process for Submission to the

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 Process for Submission to the IRB

This section will cover:
1. New Applications

2. Continuing Review (progress
3. Requests for Revision to
4. Adverse Events/Unanticipated
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 IRB forms and Instructions are posted at

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IRB forms and Instructions are posted at

From the
ORA web

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IRB forms and Instructions are posted at

From the
IRB web

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 IRB forms and Instructions are posted at

Each of the forms are available as
 hyperlinks on the forms list.
The new application form includes a
 checklist that details each of the IRB
 forms that are required for your new
Form specific instructions are also
 available for download by clicking on
 the LINK in the third column

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      When in doubt- read the
Instructions and helpful tools are
  available for download.
From the IRB forms page, select the
  first item on the list,
How do I submit an IRB application –
  and other guidance

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     How to submit an application to
                the IRB
1.      Develop a research plan/grant application or
        obtain a study protocol from the sponsor
2.      Obtain required forms for IRB review from the
        ORA website
        refer to IRB application checklist and instructions for further
3.      Determine when the application is due
           Deadlines are posted on the IRB web page and are
            labeled “Deadline/Meeting dates”
           In most* cases, any of the three Lifespan IRBs can
            review an application for use at a Lifespan affiliate.
     * Special circumstances for research to be conducted at
       Bradley or Newport, and research involving prisoners

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     How to submit an application to
                the IRB
4.      Do you need Full Board, Expedited, or Exempt
        review? Reminder: Expedited/exempt projects do not have a
        deadline and only require 2 complete copies.

5.      Financial Considerations before you submit your
               provide Dept cost center if internally funded,
               submit business forms to Grants and Contracts Office if
                externally funded

6.      Submit the completed application, with the
        required number of copies, to Review Committee
        staff by the due date.

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 What happens Next?
1.     Research Review Committee staff review the
       submitted application for completeness. After
       the application is accepted, it is processed for
2.     Expedited/Exempt projects – Research Review
       Committee staff will contact the PI when the item
       comes back from the reviewer
3.     Full Board Review -Applications that are
       accepted for full board review are placed on the
       agenda for the next committee meeting. Principal
       Investigators, or their representatives, are
       required to appear before the committee to
       address any questions or concerns raised by the

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 What happens Next?

3. After the IRB meeting, Review Committee staff
       prepare the minutes from the meeting and send
       a summary of the application discussion and
       comments to the investigator.
4.     Investigators make the committee required
       changes and return any requested
       information/clarifications to Review Committee
5.     Review Committee staff verify that the requested
       corrections have been made and process
       approval as appropriate.

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 What happens Next?

6. If the study is funded by an external source
    (grant/contract), then the approval letter will
    specify that the project is approved but not
    activated and that no activity is allowed until the
    activation is in place. When the grant/contract
    has been finalized, an activation notice with the
    new cost center will be sent to the investigator
    from the Grants and Contracts Office. If the
    project will use Dept. funds, and a cost center
    has been provided, then the IRB approval letter
    will also include an activation notice.

    Investigators cannot begin any project involving
    human subjects until IRB approval and financial
    activation have been received.

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Congratulations, Your Study Has
  Been Approved! Now What?
Projects are approved for a period up to 12
   months. The IRB may require more
   frequent review depending on the level of

Before IRB approval expires, Review
   Committee will send a progress report to
   be completed by the PI. It is ultimately
   the PIs responsibility to submit the
   continuing review report in a timely
   fashion to ensure a lapse in IRB approval
   does not occur.
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    Congratulations, Your Study Has
      Been Approved! Now What?
   Be sure to answer all questions. Follow the
    checklist at the back of the progress report to
    ensure that all required documents have been
   Progress reports are processed and reviewed in
    the same manner as new applications.
Please note the following:
    Continuation of the project beyond the
    anniversary date is contingent upon submission
    of this report. If the progress report is not
    received by the due date, approval will expire
    and no work will be allowed until the report is
    submitted, reviewed, and approved.

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 Steps to submitting a Request for Revision
      to Protocol for review by the IRB

1. Determine which aspects of the
   project will be revised (e.g. protocol,
   consent forms, advertisements,
   personnel, etc)
2. Obtain required form for IRB review
   from the ORA website and submit
   with all required attachments

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Steps to submitting a Request for Revision to
        Protocol for review by the IRB

  If the revision includes information
  that must be communicated to
  currently enrolled subjects (such as
  altered schedules, revised
  compensation, newly identified side
  effects), then you must describe the
  plan for notifying enrolled subjects
  and attach any documentation that
  will be used for this purpose.

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Steps to submitting a Request for Revision to
        Protocol for review by the IRB

  Most minor revisions can be processed for
  expedited review.
  Changes which substantially alter the
  protocol, or change the Risk:Benefit ratio
  require review by the convened IRB (full
  board review). Contact the IRB
  Coordinator/Manager for guidance.
  Please Note: The IRB Chairperson has
  the authority to refer any item to the full
  board for review.

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 Reporting Unanticipated Problems
The principal investigator must report to the IRB those
unanticipated problem/adverse events occurring
locally or at another site, that are:
specific to a study approved by a Lifespan IRB, and
involve risk to human subjects or others (i.e.
subject family members, research staff) and are:
Unanticipated, serious, and related to the research
activity; Or, are
Expected but occurring at greater frequency or
severity than anticipated. Or,
The AE indicates an increase in the risk to
participants, regardless of severity

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Reporting Unanticipated Problems
The principal investigator must also report to the
•  any deviations from the protocol or an accidental or
unintentional change to the protocol taken without prior IRB
approval to eliminate apparent immediate hazard to a research
participant (submit a deviation report for this event as well);
• a breech in confidentiality that may involve risk to that
individual or others;
• a complaint of or from a participant that indicates an
unanticipated risk or which cannot be resolved by the research

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Reporting Unanticipated Problems

Adverse Event and Deviation Reporting
forms are posted on the IRB webpage at

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                   Part 5

            Informed Consent
           It’s a Process …not a form

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      Historical Background

The requirement that researchers obtain
informed consent from research subjects
originates with Principal 1 of the
Belmont Report: Respect for Persons

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               Respect for Persons
    Individuals are treated as autonomous agents.
     This means that the subjects are not
     controlled by others and are able to make
     independent decisions
     Persons with diminished autonomy are given
     protection (e.g. vulnerable subjects such as
     children, prisoners, mentally disabled)
    Consent to participate in research is voluntary
     and informed

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     Informed Consent - Process

 Informed consent is a process
 that begins when you first
 approach the potential
 research subject and
 continues throughout the
 course of the study.

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     Informed Consent- Process

The first contact with research
subjects may be through any of the
      direct advertising

      medical record review to

       screen for eligible subjects
      physician referral

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               Informed Consent - Process
    Obtaining Informed Consent involves:
   Providing information to the subject in a language
    that is understandable to the subject or their
   Ensuring that the subject understands what they
    are being asked to do
   Answering any questions that the subject may have
   Allowing enough time for the person to think about
    the research before consenting to participate
   Obtaining voluntary agreement of the subject to
    participate in the study

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     Informed Consent - Process

The consent process continues each time that
an investigator has contact with a research

The consent dialogue is renewed every time that
the study is revised, or if new information
becomes available that would impact upon a
subject’s decision to participate,

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        Informed Consent - Elements
     Elements of informed consent:
1.   Information that the study involves research
2.   Risks or discomforts
3.   Benefits
4.   Alternatives
5.   Confidentiality
6.   Compensation/treatment offered
7.   Contact for additional information
8.   Contact information for research subject rights
9.   Statement that participation is voluntary

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   Informed Consent - Waivers
Federal regulations allow for some types of
research to be conducted without obtaining
written informed consent from research

Typically, waivers are only granted for studies
that present no greater than minimal risk. The
most frequent types of studies that are eligible
for waivers are chart reviews and surveys.

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 Want to learn more about research
            and the IRB?
 The Office of Research Administration has
    an online Human Subjects Protection
       course through the CITI program.
This site also offers:
  • A good clinical practice course (GCP)
  • A Recombinant DNA course

For information and instructions go to:

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   Contacts for IRB Questions
If you have any questions you can contact:

  Patricia Houser, Manager Research Review Committees and
  Communication at 444-2099

  Adrienne McParlin, Coordinator Research Review Committees at 444-3527

  Jacqui Poore, Coordinator Review Committees and Compliance at 444-2093

  Dawn Roux, Coordinator Research Review Committees at 444-7547

  Deb Temple, Manager Compliance and Training at 444-5843

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