Office of Research Integrity and Compliance Institutional Review Board Basics

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Office of Research Integrity and Compliance
Institutional Review Board Basics

• August 14, 2008

Annie Munana, Director ORIC Ellen Brooks, PhD,
IRB Chair April Baker, IRB Manager Melanie Mace,
IRB Manager Johari Harris, Research Compliance
Coord. Patty Zavalza, Research Compliance
Coord. Andrea Slay, Sr. Admin. Asst.
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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.

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Key Definitions of Human Subjects Research, contd

• HUMAN SUBJECTS Individuals whose physiologic or
  behavioral characteristics and responses are the
  object of study in a research projectliving
  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 subjects voluntary
  agreement, based upon adequate knowledge and
  understanding of relevant information, to
  participate in research or to undergo a
  diagnostic, therapeutic, or preventive procedure.

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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.

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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

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IRB Responsibilities, contd

• Has the authority to SUSPEND or TERMINATE
  previously approved research that is NOT being
  conducted in accordance with the IRBs
  requirements or under CFR and GCP standards, or
  that has been associated with unexpected serious
  harm to subjects

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Principal Investigator Responsibilities

• Comply with Human Subjects Education Requirement
  for themselves as well as key personnel
• Design and Implement Ethical Research Studies
• Comply with Code of Federal Regulations and Good
  Clinical Practice Standards
• Obtain prior IRB Approval and comply with IRB
  requirements
• Comply with HIPAA Requirements if PHI is accessed
  as part of the research

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Principal Investigator Responsibilities, contd

• Implement Research as Approved and Obtain Prior
  Approval for Modifications
• Obtain Informed Consent/Assent/Authorizations
• Document Informed Consent/Assent/Authorizations
• Track study expirations and submit Continuing
  Review progress reports in a timely manner
• Report Unanticipated Problems
• Retain Records and Document Activities

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Types of Submissions

• Initial Review New Studies
• Annual Continuing Review
• Amendments - Revisions
• Unanticipated Problems
• Emergent Requests (Medical)
• Final Report/Inactivations

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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 subjects 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)

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Informed Consent

• Process
• Documentation
• Alterations and Waivers

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Informed Consent

• Use the CMH format and follow all IRB
  requirements
• Use the current template located on the IRB
  website
• Signature section in each form is different
• Version date in footer do not use auto-date
• Only use IRB-stamped consents
• Complete all blanks
• Review IRB policy regarding translated consents
  for non-English speaking families

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Informed Consent

• Subjects reaching the age of 12 should sign an
  assent document
• 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.
• Consent forms should use lay language
  descriptions of common medical terms.

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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

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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.

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IND/IDE

• Stands for Investigational New Drug/Investigationa
  l Device Exemption
• If the sponsor hold the IND/IDE number, please
  provide that number in the submission.
• INDs can also be held by the PI See IRB policy
• Must secure cross-reference letter from
  drug/device manufacturer
• PI submits IND/IDE application to FDA
• Annual reports are required for FDA

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Investigator-Held IND/IDE

• Guidance For Evaluation
• The protocol is NOT intended to be reported to
  the FDA in support of a new indication for use or
  to support any other significant change in the
  labeling for the drug.
• The protocol is NOT intended to support a
  significant change in the advertising for the
  product.
• The protocol does NOT involve a change in route
  of administration or dosage level, use in a
  subject population, and other change/factor that
  significantly increases the risks (or decreases
  the acceptability of the risks) associated with
  the use of the drug product.

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Investigator-Held IND/IDE

• If the answer to all points are true, then PI
  does not need to submit to FDA.
• If any point is false, an IND/IDE application is
  required. Contact the FDA regarding application
  process.
• Provide the IRB with a copy of the FDA
  correspondence issuing the assigned number
• IRB requires copy of annual report to FDA at the
  time of continuing review

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Types of Review

• Exempt
• Expedited
• Minimal Risk
• Full Committee Review
• Minimal Risk
• Greater than Minimal Risk

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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

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Mechanism of ReviewExpedited Research

• Expedited does not necessarily mean a fast review
  It simply means it does not require full board
  review
• 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
• Only minimal risk studies in Federally-defined
  categories can be expedited

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Continuing/Annual Review

• PIs are responsible for monitoring the approval
  periods for their studies.
• Must be done no less than annually for ongoing
  studies
• More frequent review may be necessary for some
  research studies as IRB determines
• As a courtesy, IRB sends out progress report
  notices approx. 2-3 months prior to the studies
  expiration date
• If PI holds an IND/IDE for the study, the IND ,
  Date of issuance and a copy of the most recent
  annual report to FDA must be included in the
  submission.

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Amendments and Revisions

• Require approval before implemented (unless to
  eliminate immediate safety issue)
• Evaluate impact of change risk/benefit assessment
• Minor changes may undergo expedited review
• Submit a cover letter summarizing the changes and
  tracked and clean versions of revised documents

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Unanticipated Problems/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.
• Please refer to the IRB Policy for submitting
  unanticipated problems

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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.htmlemerg
  ency
• Intended to be used only once

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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

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Types of Approval

• Approved without Contingencies
• Approved with Contingencies
• - minor directed
• - major
• Tabled
• Disapproved/Rejected

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Approved without Contingencies

• No revision is necessary to any submitted
  document
• Provided all administrative contingencies are
  met, the approval paperwork can be released

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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

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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

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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 meetings agenda

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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

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Education/Personnel Form

• To be included in addition to names on OSP form
• Requires the listing of all research personnel
  who have a significant role in the study
• All listed personnel must be current in human
  subjects education Requirement for
  certification on IRB website
• Will be required with every new study and
  continuing review submission
• Names of certified staff are posted on IRB website

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IRB STATS FY 2008Expedited Review Submissions
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IRB STATS FY 2008Full Board Review Submissions

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IRB UPDATES

• SAE Submissions for registry or observational
  studies
• Complete Submissions including Personnel Form and
  potential additional Division and Dept Head
  Signatures
• IRB Application Form - Coming Soon
• AAHRPP Application
• New Policies (proxy consent, Acting PI,
  electronic continuing review notices)

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Questions and Answers