IRB Review Criteria

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• IRB Review Criteria
• Jeffrey M. Cohen, Ph.D., CIPPresident,
• HRP Associates, Inc.

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Criteria for IRB Approval
46.111

• When appropriate
• data collection is monitored to ensure subject
  safety
• privacy and confidentiality of subjects is
  protected
• additional safeguards are included for vulnerable
  populations

• Risks to subjects are minimized
• Risks are reasonable in relation to anticipated
  benefits
• Selection of subjects is equitable
• Informed consent is sought from each subject
• Informed consent is appropriately documented

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Criteria for IRB Approval
46.111
Subject selection Inclusion/exclusion Recruitment
Risk/Benefit AnalysisData Safety Experimental
Design Qualifications of PI
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IRB Decision Matrix
Subject selection Inclusion/exclusion Recruitment
Risk/Benefit AnalysisData Safety Experimental
Design Qualifications of PI
J. Cooper, AAHRPP
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• Risk/Benefit

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Risk

• IRB Responsibilities
• Identify Risks
• Determine that risks are minimized
• Determine that risks to subjects are reasonable
  in relation to anticipated benefits
• Determine that subjects are adequately informed
  about any reasonably foreseeable risks or
  discomforts

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Identifying Risks

• IRBs should not rely solely on investigators to
  identify risks
• No one can be objective about their own work
• People underestimate the risks involved in things
  they are very familiar with
• People overestimate the benefit of things that
  are important to them

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Identifying Risks

• The term risk involves two dimensions
• Magnitude of harm
• Probability of harm
• Assessing the level of risk involves taking both
  into account

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Social Psychological Risk

• Social Psychological risks are real risks

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Minimizing Risk

• Three ways to minimize risk
• Alternatives
• other procedures that are less risky
• Precautions
• procedures to decrease the likelihood that harms
  will occur
• Safeguards
• procedures to deal with harms if they occur

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Risk/Benefit

• Evaluation of Risk/Benefit ratio is subjective
  judgement
• IRB must decide whether the anticipated benefit
  justifies asking subjects to undertake the risks
• Should take into account different subject
  populations and individual differences among
  subjects

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• Subject Selection Recruitment

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Subject Selection

• Justice requires equitable distribution of both
  the burdens and benefits of research
• Individuals and groups that bear the burden
  should share in the benefits
• Individuals and groups that benefit from research
  should share in the burden
• Selection of subjects should be justified by the
  science
• IRBs should not overprotect vulnerable
  populations so that they are excluded from
  participating in beneficial research
• If the study is funded by NIH, exclusions of
  women, minorities or children MUST be justified.

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Subject Recruitment

• Subject recruitment is part of the consent
  process
• Information in recruitment should be consistent
  with protocol
• Recruitment should not be coercive or unduly
  enticing
• Recruitment should clearly indicate that it is
  for research and not make unfounded claims (e.g.,
  cure or free treatment)
• IRBs must review recruitment procedures,
  including any advertising
• Difference between FDA and OHRP guidance

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Informed Consent
Beyond the Consent Form
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The Consent Process

• Informed consent is not a single event or just a
  form to be signed -- rather, it is an educational
  process that takes place between the investigator
  and the prospective subject.
• The basic elements of the consent process
  include
• full disclosure of the nature of the research and
  the subject's participation,
• adequate comprehension on the part of the
  potential subjects, and
• the subject's voluntary choice to participate.

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Tampa Tribune 3/11/00

• TAMPA - A lawsuit accusing USF doctors of
  experimenting on pregnant women without their
  consent is settled for 3.8 million. The
  experiment wasn't considered risky and no adverse
  effects were documented, plaintiffs in the suit
  agree. However, the failure to inform pregnant
  women of various experiments conducted between
  1986 and 1990 has cost Tampa General Hospital,
  USF and the state 3.8 million.

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Informed ConsentBasic Elements
46.116(a)

• Confidentiality
• Compensation for Injury
• Whom to Contact
• Right to Refuse or Withdraw

• Research
• Purpose/Duration
• Procedures
• Experimental
• Risks
• Benefits
• Alternatives

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Informed ConsentAdditional Elements
46.116(b)

• Currently Unforeseeable Risks
• Termination of Participation
• Additional Costs to Subjects
• Consequence of Withdrawal
• Informing of New Findings
• Number of Subjects

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Comprehension

• Informed consent is not valid unless the
  prospective subject understands the information
  that has been provided.
• It is the responsibility of the investigator to
  do what he/she can to enhance each prospective
  subject's comprehension of the information.
• The investigator must consider the nature of the
  proposed subject population, the type of
  information to be conveyed, and the circumstances
  under which the consent process will take place
  in determining the appropriate way to present the
  information.

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Comprehension

• Avoid technical terms
• Translation
• Language is appropriate to their age level
• Different consent procedures may be required with
  different populations.

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Voluntary Consent

• Only legally competent adults can give consent
• Minors cannot give consent
• Incompetent adults cannot give consent
• The evaluation of competence must be made on a
  case by case basis.

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Voluntary Consent

• Assent
• "knowledgeable agreement" to participate
• whenever the potential subject has sufficient
  capacity to understand what is happening and
  express his/her wishes.
• "deliberate objection" is veto of the consent of
  a parent or guardian (unless there is direct
  benefit to the subject)

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Voluntary Consent

• In order to be valid, consent must be freely
  given. That means that it is free from all forms
  of coercion.
• In addition to overt coercion, the investigator
  needs to be sensitive to more subtle forms of
  coercion, such as social pressure, requests from
  authority figures, and undue incentive for
  participation.

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Procedures for Obtaining Consent
46.116

• Subject has the legal and mental capacity to give
  consent
• legally authorized representative
• Sufficient opportunity is provided to consider
• The possibility of coercion or undue influence is
  minimized
• Language understandable to the subject
• No exculpatory language

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Consent Pitfalls

• Whatever you say, Doc
• Therapeutic misperception
• Timing of consent
• Fear of reprisal for not participating
• Reluctance to admit they dont understand

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Documentation of Consent
46.117

• Legally effective informed consent"
• written consent form signed by the subject or the
  subject's legal representative.
• The consent form is merely the documentation of
  informed consent
• The fact that a subject signed a consent form
  does not mean that he/she understood what was
  being agreed to or truly gave their voluntary
  consent.
• Informed consent is a process which is documented
  by a signed consent form.

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Documentation of Consent

• It is recommended that consent forms meet four
  criteria
• Be brief, but have complete basic information.
• Be readable and understandable to most people.
• Be in a format that helps people comprehend and
  remember the information.
• Serve as a script for the face-to-face
  discussions with the potential subjects.

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Documentation of Consent

• Reading Level
• Maximum 8th grade reading level (preferably
  lower)
• ordinary language
• active tense
• shorter sentences
• logical sequences

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Documentation of Consent

• Format can help comprehend and remember complex
  material. Good format uses headings indents
  bolded type lists extra spacing between
  sub-topics repetition reasonable-size type and
  plenty of margins and empty space in general.

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Documentation of Consent

• Format can help comprehend and remember complex
  material. Good format uses
• headings
• indents
• bolded type
• lists
• extra spacing between sub-topics
• repetition
• reasonable-size type and
• plenty of margins and empty space in general.

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Data Safety Monitoring
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Data Safety Monitoring

• Oversight and monitoring to ensure the safety of
  participants and the validity and integrity of
  the data
• NIH Data Safety Monitoring Policy
• For phase I and II clinical trials, investigators
  must submit a general description of the data and
  safety monitoring plan as part of the research
  application. For phase III clinical trials a DSMB
  is required

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Privacy and Confidentiality
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Definitions

• Privacy - having control over the extent, timing,
  and circumstances of sharing oneself (physically,
  behaviorally, or intellectually) with others.
• Confidentiality - methods used to ensure that
  information obtained by researchers about their
  subjects is not improperly divulged.

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Regulations

• 46.102(f) Human subject means a living individual
  about whom an investigator conducting research
  obtains
• (1) data through intervention or interaction
  with the individual,
• or
• (2) identifiable private information.

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Regulations

• Private information - information which has been
  provided for specific purposes by an individual
  and which the individual can reasonably expect
  will not be made public (for example, a medical
  record).
• Identifiable information information where the
  identity of the subject is or may readily be
  ascertained by the investigator or associated
  with the information.

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Confidentiality

• Confidentiality and anonymity are not the same
• Anonymous means no one, anywhere, ever can
  identify individual subjects
• Names are not the only identifiers
• Subjects participation in the research may need
  to be kept confidential as well as their data

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Confidentiality

• More elaborate procedures may be necessary for
  studies in which data are collected on sensitive
  matters such as sexual behavior or criminal
  activities.
• Any written record linking subjects to the study
  can create a threat to confidentiality, including
  consent forms

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Vulnerable Populations
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Vulnerable Populations

• Federal regulations involving human subjects in
  research include specific protections for
  children, pregnant women and fetuses (Subpart B),
  prisoners (Subpart C), and children (Subpart D).
  
• In addition, the IRB expects the investigator to
  provide additional information regarding
  cognitively impaired individuals in research or
  others who are likely to be vulnerable to
  coercion or undue influence.

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Conclusion

• The IRB must be satisfied that all of the review
  criteria have been met before it approves a
  protocol
• The IRB must have sufficient information upon
  which to base its decision
• OHRP frequently cites IRBs for not having enough
  information to make a decision