The IRB: Friend or Foe?

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The IRBFriend or Foe?

• Margaret J. Neff, MD MSc
• Assistant Professor of Medicine
• Pulmonary Critical Care Medicine

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Getting things through the IRB

• Why does it matter?
• Basic requirements
• Lay-out of the UW IRB
• Specific scenarios
• Screening, consent, database reviews
• Helpful tips

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Past Research

• 1930s-40s Nazi war
• crimes experiments

• 1971 Stanford Prison
• Experiment

• 1932-1972 Tuskegee
• Syphilis Experiment

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Recent Research

• 1999 U Penn gene transfer study (Jesse
  Gelsinger) followed incl/excl criteria?, safety
  monitoring?, informed consent?, conflict of
  interest?

• 2001 Johns Hopkins asthma study (Ellen Roche)
  hexamethonium who is responsible for researching
  safety?

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Common Themes

• Lack of informed consent
• Risk gtgtgtgtgt benefit
• Risk assessment not complete
• Vulnerable populations
• Students employees
• Poor safety oversight
• Conflict of interest

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Troubled Waters

• Penn
• Duke
• Johns Hopkins
• U of Illinois-Chicago
• U Colorado
• West LA VA
• Rush Presbyterian
• Virginia
• Not a list we want to join

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Ethical Codes Guiding Clinical Research (Human
Research)

• Nuremberg Code 1947
• Declaration of Helsinki 1964
• The Belmont Report 1979

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Regulations Pertaining to Clinical Research

• U.S. Code of Federal Regulations
• Health and Human Services
• 45 CFR 46 (protection of human subjects)
• Food and Drug Administration
• 21 CFR 50 (protection of human subjects)
• 21 CFR 56 (institutional review boards)
• State Law
• Washington Administrative Code (WAC)
• Institutional policies, sponsor

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Criteria for approval of research

• Risks minimized and reasonable in relation to
  anticipated benefits
• Subject selection is equitable
• Informed consent sought
• Informed consent documented
• Plan data safety monitoring
• Provisions for privacy/ confidentiality
• Additional safeguards for vulnerable populations

www.access.gpo.gov/nara/cfr
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Design of IRB

• At least 5 members
• Varying backgrounds, gender
• At least 1 scientist 1 non-scientist
• At least 1 not affiliated with institution
• No conflict of interest with study reviewing
• May invite consultants to review

www.access.gpo.gov/nara/cfr
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Univ. of Washington IRB

• Multidisciplinary membership
• MDs, RNs, pharmacists, lawyers, students,
  community members
• 6500 protocols reviewed/year
• 10 committees
• 3 biomedical, 3 behavioral, 3 minimal risk, 1 VA
• Full-time staff but other members are primarily
  volunteering their time
• Western IRB now used for all industry-sponsored
  trials

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When do you need IRB approval?

• When youre conducting human subjects research
• Any study where results are intended for
  dissemination as research (vs QI)
• Patient info or patient samples
• Waiver of consent possible in some instances
• De-identified data
• 18 specific data points removed
• Limited data set
• Meet specific criteria (emerg research records
  review, etc)

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Types of Review

• Full committee review
• Most studies
• Expedited review
• Generally only for database/registry work
• No patient contact, no interventions
• Using data already available
• May qualify for certificate of exemption

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General Issues Prior to Review

• Do you have the resources to do it?
• Coordinator? Funds? Enough time?
• Any financial conflict of interest?
• Taken ethics/IRB training?
• Required for NIH and VA studies soon for all UW
  studies
• Clinical Research Budget Billing
• Made contact

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The IRB Submission Process

• Complete application, get dept signatures
• Submit application (include a cover letter with a
  howdy, heres what were doing and address any
  anticipated problem points brief)
• Once at the IRB
• Pre-screening
• Full review with deferral or approval
• Committee letter
• Your response
• Re-evaluated in sub-committee
• Back to full committee, hopefully to approve

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Who is it youre hearing from?

• Each committee
• Chair, members, administrator, and coordinators
• The administrator pre-screens the study and often
  contacts you for clarifications prior to first
  review
• Get to know this person
• If complex study, go and meet
• Offer to come to the committee meeting (or be
  available by phone) if anticipated
  questions/problems
• Be nice and not defensive

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Some common pitfalls

• Application should be understandable to an
  educated, lay audience (the IRB members)
• Avoid lots of cutting and pasting of text
• Be organized! Be consistent.
• Make it easy to read (not tiny font)
• Think of it like a grant youre submitting
• Be thorough and follow the instructions
• Appropriate copies, answer all questions
• If you dont know what they mean, ask!

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Screening/Recruitment

• Screening for potential subjects
• Waiver of consent for screening
• Confidentiality agreement
• Need to report each time access chart
• Recruitment
• Include any flyers or website notices
• Generally try to allow potential subjects to call
  you rather than cold calls.

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Subject approach

• Avoid any appearance of coercion
• Initial introduction by non-research personnel
• Ideally have clinical personnel separate from
  research personnel

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Privacy/Confidentiality

• Minimize identifiable information on data
  collection forms no names
• No identifiable elements on screened,
  non-enrolled (non-consented) subjects
• Describe mechanism for safeguarding data
• Plan for destruction of any links and the data as
  soon as possible (but feasible)

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Risks and Benefits

• Dont exaggerate the benefits
• Be honest about the risks
• Usually death is always a risk in any
  intervention study
• Often useful to group by common and rare risks
• How youll deal with any adverse events
• Who pays?
• Who pays for research studies?
• In most cases, its the sponsor
• For NIH or investigator initiated UW
  Compensation plan

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Consent

• Utilize the consent template (some standard
  wording and sections)
• Assent form for children as well
• Language
• 8th grade reading level
• Subject not patient
• Go through consent checklist

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Obtaining Consent

• Subject needs adequate time and information to
  make a decision
• Competency must be assessed
• If limited, at minimum need assent
• Consent is invalid if subject is pressured or
  coerced
• Ideally assess comprehension

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Who Can Consent?

• Subject him or herself
• Legally authorized representative
• This varies state-to-state whether allowed and
  what order is followed
• In Washington, its based on WAC guiding clinical
  decision making, extrapolated to research
• Guardian, Subject, DPOA-HC, spouse, adult
  children, parents, adult siblings
• Who consents for clinical procedures may vary but
  for research, this order is strictly adhered to
• Recent changes clinically for domestic partners

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Waived Consent for Emergency Research

• Should the needs of the many ever outweigh the
  needs of the one?
• Waived consent (e.g. pre-hospital, MI, stroke)
• Specific criteria must be met and documented
• If criteria for waived consent are met
• No more than minimal risk
• Will not adversely affect rights of subjects
• Research not practical without waiver
• Provide info to subjects at later date
• May require survey and notification of community

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Other Issues

• Federal Certificate of Confidentiality
• If sensitive questions about drug and alcohol
  abuse
• Vulnerable subjects
• Prisoners, pregnant women, children
• Registration of clinical trials

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Tips for Interacting with the IRB

• They are there to help you and to protect the
  subjects and the ability to do research here at
  all!
• Research is a privilege, not a right
• Be prompt in responses
• Be cordial

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• May not be consistent committee to committee
• Each is independent but this is improving moving
  towards sending all of 1 type of specialized
  study to 1 committee

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• There may be delays and lots of questions that
  seem not relevant
• Theyre trying to best understand the study
• If you dont understand what theyre getting at,
  call them. Maybe they didnt understand
  something youre trying to do.
• Offer to meet the administrator or go to the
  meeting. Resolve the problems up front.
• Try to explain your intent

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Resources

• IRB website
• http//www.washington.edu/research/hsd/
• Clinical Research Budget Billing
• http//www.uwmedicine.org/Research/
  ResearchBudgetBilling/
• HIPPA resources
• http//privacyruleandresearch.nih.gov/
• http//www.hhs.gov/ocr/hipaa/
• Me mneff_at_u.washington.edu

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