Navigating the IRB Process

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Navigating the IRB Process
Enhancing Integrity in Clinical Research June 3,
2005
Barbara G. Bigby, MA, CIP Director, Scripps
Office for the Protection of Research Subjects
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Erosion of Public Trust in Research

• (Investigator Sponsor IRB)
• Protect subjects
• Increase public trust
• Sustain the research effort

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(No Transcript)
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The New England Journal of Medicine September
14, 2000 -- Vol. 343, No. 11

• Protecting Research Subjects -- What Must Be
  Done
• -Donna Shalala, Ph.D
• clinical researchers and the institutions that
  support them must, without exception, maintain
  the public's confidence in our work, our
  competence, and most important, our ethics.

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Erosion of public trust after the death of Jesse
Gelsinger.

• Unreported adverse events
• Not enough resources are allocated to protecting
  human subjects
• No full disclosure of risks
• Coercive recruitment practices
• Loose adherence to GCP
• IRBs are broken

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Tuskegee Survivor
President Clinton formally apologized for
Tuskegee in 1997. Mr. Shaw died December 3,
1999, at the age of 97
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Many Patients, Particularly African Americans,
Do Not Trust Their Doctors, Survey Indicates
Almost 80 of African Americans and 52 of whites
believe they could be used as guinea pigs for
medical research without their consent, according
to a study on patients' trust of the medical
establishment published in the Nov. 26 Archives
of Internal Medicine. (Fackelmann, USA Today,
11/26/02)
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The National Research Act

• Established in 1974 in response to the exposé of
  the Tuskegee Syphilis Study
• National Commission for the Protection of Human
  Subjects of Biomedical and Behavioral Research
  met from 1974-1978 in the Belmont Conference
  Center of the Smithsonian Institution

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The Belmont Report

• Report of the National Commission
• Published in 1979
• Triggered by Tuskegee and other abuses
• Called for oversight of research by Institutional
  Review Boards

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The Belmont Report

• Basic Ethical Principles
• Respect for persons
• Beneficence
• Justice

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The Belmont Report

• Respect for persons
• Autonomy (need for consent)
• Protection of persons with diminished autonomy
  (children, mentally disabled, pregnant women,
  prisoners, etc.)

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The Belmont Report

• Applications
• Informed Consent
• Information
• Comprehension
• Voluntariness

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The Belmont Report

• Beneficence
• Do no harm
• Maximize benefits
• Minimize risks

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The Belmont Report

• Applications
• Assessment of Risks and Benefits
• The Nature and Scope of Risks and Benefits
• The Systematic Assessment of Risks and Benefits

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The Belmont Report

• Justice
• Subject selection
• Distribute risk and benefit fairly
• Fairness in inclusion/exclusion criteria

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The Belmont Report

• Applications
• Selection of Subjects
• Individual justice requires that researchers
  exhibit fairness
• Social justice requires that distinction be drawn
  between classes of subjects that ought and ought
  not to participate in any particular kind of
  research

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Circle of Trust Respect
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OHRPs Motto
Doing it Right Together "Always do right -
this will gratify some and astonish the rest."

- Mark Twain
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Why cant I use an independent IRB?

• Institutional policy need for local oversight
• Federal Wide Assurance

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The IRB and the Investigator should be Partners..

• Neither the investigator nor the IRB can know
  everything -
• Experts on the IRB can help an investigator write
  a protocol that is both scientifically valid and
  as safe as possible.
• IRBs must recognize when they need to seek
  outside expertise to ensure a fair review.

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Using Belmont to guide IRB/Investigator
Relationships

• Be respectful
• Do no harm (to the relationship)
• Be fair

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Trust Requires Knowledge

• In order to trust their IRB, Investigators must
• Know the Chair is she a scientist? Has she
  submitted her own protocols to the IRB?
• Know the backgrounds of the members who serve
• Ask about the experience of the IRB staff -- what
  skills and experience do they bring to their
  roles?

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Respect Requires Trust

• The IRB must trust that the PI will do
  everything possible to protect research subjects
  --
• Ensure that investigators and staff are trained
  in procedures required by the protocol
• Follow the research protocol wait for IRB
  approval before instituting modifications to an
  existing protocol
• Ensure that informed consent is a process, not
  just a form
• Report all serious and unexpected adverse events
• "Sometimes it is not enough to our best we must
  do what is required."
  - Sir Winston Churchill

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Knowledge Requires Communication

• IRBs and investigators must communicate
  effectively. IRBs should - -
• Streamline the application process
• Differentiate between regulation (law) and
  interpretation (judgment)
• Provide respectful feedback to investigators

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Knowledge Requires Communication

• IRBs and investigators must communicate
  effectively. Investigators should - -
• Read and critique proposed consent forms
• Submit complete and understandable applications
• Be available for questions

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Respect Requires Trust

• The research team must trust the IRB to do its
  job - -
• Understand the role of the IRB versus the role of
  the support staff
• Trust that the IRB knows federal and local
  regulations governing the use of humans in
  research

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Respect Requires Trust

• The IRB must trust the investigator and the
  research team to - -
• Tell the IRB how risks will be minimized
• Ensure that staff are trained in human subjects
  protection and the procedures required by the
  protocol
• Provide information about why our institution and
  our patients should participate in the proposed
  research

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The IRB/Investigator relationship is based on
trust

• Regulations are only part of the picture
• "Good people do not need laws to tell them to act
  responsibly, while bad people will find a way
  around the laws."
• - Plato

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Human subject protection requires commitment by
the institution and the investigator

• "The difference between 'involvement' and
  'commitment' is like an eggs-and-ham breakfast
  the chicken was 'involved' - the pig was
  'committed'."
• - unknown

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• Overview
• Questions IRBs Must Ask
• Composition of an IRB
• Role of the IRB
• IRB Review of Research

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Questions IRBs must ask...

• Does the scientific merit warrant putting
  subjects at risk?
• Have the risks been minimized as much as
  possible?
• Are the risks and benefits (personal and to
  society) in reasonable balance?
• Is the information and consent process adequate?

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Composition of an IRB

• Federal Regulations require that
• An IRB have at least five members
• At least one of those members must be a
  non-scientist
• Membership includes both scientists and
  non-scientists
• Membership includes people linked to the
  institution and people independent of it
• Membership includes people with useful
  expertise in science, ethics, law, and community
  concerns

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Composition of an IRB

• The IRB cannot
• Be composed of all men or all women
• Have members from only one profession
• Allow investigator/members to participate in the
  discussion or vote on their protocols

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Role of the IRB

• To protect human subjects from inappropriate risk
  through
• Prospective review of new research proposals
• Continuing review of ongoing research

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IRB Review of Research

• When reviewing a research protocol, the IRB has
  the authority to
• Approve the protocol
• Require modifications to the protocol
• Disapprove the protocol

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Ethical Review by an IRB

• Risks to subjects are minimized by use of sound
  research design and incorporation of diagnostic
  procedures, whenever possible
• Risks are reasonable in relation to anticipated
  benefits to subjects
• Selection of subjects is equitable
• Informed consent will be obtained and documented

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Ethical Review by an IRB

• Where appropriate, the research plan makes
  provisions for monitoring the data collected to
  ensure the safety of subjects
• There are provisions to protect the privacy of
  subjects and to maintain the confidentiality of
  data
• Additional safeguards exist to protect vulnerable
  subjects

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Resources for IRBs

• Public Responsibility in Medicine and Research
  (PRIMR)
• Applied Research Ethics National Association
  (ARENA)
• IRB Forum
• FDA and OHRP web sites

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Resources for Investigators

• PRIMR and ARENA
• http//www.primr.org
• FDA Home Page
• http//www.fda.gov
• OHRP
• http//www.hhs.gov/ohrp/
• Bioethics
• http//bioethics.net/
• http//www.nih.gov/sigs/bioethics/
• http//www.bioethics.upenn.edu/
• http//ethics.sandiego.edu

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Resources for Investigators
Centerwatch www.centerwatch.com
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Research has evolved over the last decade

• Increased federal and private funding
• Questionable recruitment practices
• Patients as subjects
• Physicians as investigators
• The potential for conflicts of interest is more
  widely appreciated

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Research has evolved over the last decade

• Increased emphasis on research in the media
• Activism by groups anxious to right wrongs or
  gain access to new drugs, devices, procedures
• In particular, activism by women, HIV-infected
  individuals and cancer patients

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Research has evolved over the last decade

• Higher education level of patients/subjects
• Less disparity between physician/researcher and
  patient/subject
• Old-fashioned paternalism is less likely
• to be tolerated

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Research has evolved over the last decade

• Greater demand for information, respect, and
  access to new drugs/devices/procedures
• Increased public funding
• Greater political interest in oversight of
  research
• Greater sense that research is a public activity

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New on the horizon.

• Required registration of all clinical trials --
  before IRB review
• Currently, pharmaceutical companies can run
  clinical trials without publicly disclosing their
  existence, let alone their results.
• www.clinicaltrials.gov

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New on the horizon.

• Certification for IRB staff
• Certification for investigators
• IRB registration

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• "It is better to be feared than loved,
• if you cannot be both."
• -Machiavelli

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• "Don't let it end like this. Tell them I said
  something."
• - last words of
  Pancho Villa