Human Subjects and the CHR

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Human Subjects and the CHR

• James Kahn MD
• Professor of Medicine, UCSF

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Quick Check of Terms

• CHR Committee of Human Research (UCSF term
  often used by others in UCSF)
• IRB Institutional Review Board (often used by
  persons outside of UCSF)
• For our purposes CHR IRB

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How To Make CHR Love Youand you to love them

• Dealing successfully with the IRB

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Partnership in Research
Investigator
Investigator
Participant
Institutional Officials
Institutional Officials
IRB
CHR
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What does the CHR expect?

• Consideration of how the substantive issues
  methods fit with ethical guidelines IRB
  requirements
• Clarity in statement of problem, Research
  Questions Methods of data collection
• Consistency in content of all documents
• Completeness of all materials

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What is the bottom line?

• When in doubt, ask questions seek help
• Remember consideration, clarity, consistency,
  completeness
• On-going process keep dialogue open
• CHR uses reasonable person standard to ensure
  high standards of ethical research
• CHR is more than enforcers/regulators
• Although PIs may not think so

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What is the CHRs role?

• Protection of Human Subjects
• Physical harm
• Emotional harm
• Economic harm
• Assessment of Research Risk
• Benefit to the subject
• Research methodology
• Protection of the University
• Compliance with regulations

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CHR review includes

• Ethical evaluation of the research
• Recruitment/participation
• Incentives/payments
• Recruitment procedures -- no coercion
• New information
• Analysis of unanticipated problems involving
  risks to others

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Roles and Responsibilities

• Institutional Officials
• Act as signatory official on assurances
• Provide adequate resources for IRB (staff,
  computers, office space, etc.)
• Ensure adequate placement of IRB within
  institutional infrastructure
• Negotiate contracts with sponsors
• CHR
• Protect human subjects
• Risks are minimized and anticipated benefits
  maximized
• Informed consent process adequate
• Equitable selection of subjects
• Sound scientific design

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Roles and Responsibilities

• Principal Investigators
• Protect human subjects
• Ensure all personnel comply with protocol
• Ensure all personnel comply with findings and
  determinations of IRB
• Prospectively submit changes in research to the
  IRB for approval
• Minimize undue influence in enrolling subject
• PIs Study Coordinators
• Adhere to protocol requirements
• Report adverse events and unanticipated problems
  to PI
• Ensure that informed consent process adequate and
  understandable to subjects

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Research Enterprises Closed

• Duke University
• University of South Florida
• Virginia Commonwealth University
• West L.A., V.A.
• University of Colorado
• University of Illinois, Chicago
• University of Alabama, Birmingham

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The Common Rule

• Adopted by the 16 federal agencies that conduct,
  support, regulate human research.
• Title 45 Part 46 - Code of Federal Regulations
  (1981)
• Enforce by Office of Human Research Protection
  (OHRP) formally OPRR.
• FDA adopted certain provisions - Title 21 Parts
  50 56

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What is Research?

• Research
• As defined by 45 CFR 46, "a systematic
  investigation, including research development,
  testing and evaluation, designed to develop or
  contribute to generalizable knowledge"

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Examples of Research

• Obtaining data from medical records
• Comparing two FDA approved drugs in an organized
  manner
• Running an investigational test for another site
• Doing statistical analysis for other sites
• Collecting left over tissues

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What is a Human Subject?

• "Human" subject is a living individual about whom
  an investigator obtains either
• data through intervention or interaction with the
  individual or
• identifiable private information.

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Primate Information

• Private Information means
• (1) information about behavior in a context in
  which an individual can reasonable expect that no
  observation or recording is taking place
• (2) information, provided for specific purposes,
  that the individual can reasonably expect will
  not be made public (e.g., a medical record)

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National Bioethics Advisory Commission

• The extent to which a sample is linked with the
  identity of its source significantly affects the
  risks and potential benefits.
• Examples of samples include
• Repository
• Research
• Coded
• Identified

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Categories of human biological materials

• Repository Collections
• Unidentified specimens Identifiable personal
  information was not collected or, if collected,
  was not maintained and cannot be retrieved
• Identified specimens Specimens are linked to
  personal information in such a way that the
  person could be identified by name, patient
  number, or clear pedigree location (relationship
  to a family member whose identity is known)

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Categories, cont'd

• Research Samples
• Unidentified samples Sometimes termed anonymous,
  these are samples supplied by repositories to
  investigators from a collection of unidentified
  human biological specimens
• Unlinked samples Sometimes termed anonymized,
  these lack identifiers or codes that link a
  sample to a particular human being

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Categories, cont'd

• Coded samples
• Sometimes termed linked or identifiable, these
  samples are supplied by repositories to
  investigators from identified specimens with a
  code rather than with personally identifying
  information, such as a name or Social Security
  number

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Categories, cont'd

• Identified samples
• These samples are supplied by repositories from
  identified specimens with a personal identifier
  (such as a name or patient number) that would
  allow the researcher to link the biological
  information derived from the research directly to
  the individual from whom the material was
  obtained

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NBAC Recommendations

• Research with anonymous samples is not human
  subject research
• Research with unlinked samples is human subject
  research but eligible for exemption. If unlinking
  samples, the IRB should decide if the process is
  effective and won't unnecessarily reduce the
  value of research

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NBAC recommendations -2

• Research with coded or identified samples is
  research on human subjects and subject to the
  human subject protection regulations
• Repositories should not release coded or
  identified samples to researchers without
  documentation of IRB approval

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What is Minimal Risk?

• Minimal Risk
• As defined by 45 CFR 46, "a risk is minimal where
  the probability and magnitude of harm or
  discomfort anticipated in the proposed research
  are not greater than those ordinarily encountered
  in daily life or during the performance of
  routine physical or psychological examinations or
  tests"

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Informed Consent

• No coercion or undue influence
• Language understandable to the subject
• No exculpatory language
• Eight required elements
• Six additional elements

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Eight Required Elements

• 1. Statement that study is research and
  information on purposes/duration/procedures/experi
  mental procedures
• 2. Reasonably foreseeable risks or discomforts
• 3. Benefits which may be reasonably expected
• 4. Alternative procedures
• 5. How confidentiality will be maintained
• 6. For more than minimal risk, information on
  compensation for injuries
• 7. Contact names -- at least one not associated
  with the research recommended
• 8. Statement that participation is voluntary and
  can withdraw at any time

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Six Additional Elements

• 1. Statement that there may be risks which are
  unforeseeable
• 2. Under what circumstances investigator could
  terminate subjects participation
• 3. Additional costs to subject
• 4. Consequences of subjects withdrawal from
  research
• 5. Statement that will be told of new findings
• 6. Approximate number of subjects in study

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Vulnerable Populations

• Fetuses
• Children
• Pregnant Women
• Prisoners
• Those unable to give informed consent
• because of clinical condition
• because of acute situation

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What does dealing with the CHR involve?

• Pre-submission questions (ask PI)
• Scientific or Scholarly Merit Review
  (Departmental review)
• Review of submitted protocol (CHR)
• what is the study about?
• who is involved?
• what are data collection/handling methods?
• Decisions
• More reviews
• Governed by 45 CFR 46 21 CFR 56

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What does the CHR expect?

• Consideration of how the substantive issues
  methods fit with ethical guidelines IRB
  requirements
• Clarity in statement of problem, Research
  Questions Methods of data collection
• Consistency in content of all documents
• Completeness of all materials

31
What is the bottom line?

• When in doubt, ask questions seek help
• Remember consideration, clarity, consistency,
  completeness
• On-going process keep dialogue open
• CHR uses reasonable person standard to ensure
  high standards of ethical research
• CHR is more than enforcers/regulators
• Although PIs may not think so

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A brief reminder of upcoming events

• UPCOMING CTSA Junior Faculty Forums
• Wednesday, December 14th
• 1200-100 PM  
• SF General Hospital 6th Floor, WARD 6D Room 12
• PHP HIV/AIDS Grand Rounds every Wed at 8 am
• Carr Auditorium (CME available free)
• Jim to meet with each of you individually