Presented by: Ellen Graf AOResearch Cincinnati VAMC

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Consideration of Risks and Benefits at Initial
Review

• Presented byEllen Graf AO/Research
  Cincinnati VAMC

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Lets jump-start this topic

• You are a patient in the hospital receiving
  treatment for cancer.
• You are approached by your physician regarding a
  new research protocol being conducting using
  investigational drugs that you might be
  considered eligible for.
• You agree to speak to someone about the study and
  are reviewing the informed consent and come upon
  three pages of risks..

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As a patient currently receiving chemotherapy

• Do you want to know all the risks involved?
• Are three pages of risks too much to fathom?
• Do you want to be updated as new risks are
  determined?

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A comment from a committee member made at a
recent initial review

• With all the poisons being pumped into these
  folks with the current standard treatment, they
  really dont want to know this stuff or even
  care. Do you think they care if this new drug
  causes a few heart palpitations on top of
  everything else going on with them?

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Criteria for IRB Approval

• 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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The Belmont Report Assessment of Risks and
Benefits

• Principle of beneficence is expressed in
  risk/benefit assessment
• The Nature and Scope
• A Systematic Assessment
• Must be "balanced" and shown to be "in a
  favorable ratio"

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Role of the IRB

• Assures that
• risks are proportionate to the benefit
• the research is ethical
• conducted in accordance with the principles of
  the Belmont Report and federal, state, and local
  laws and regulations

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Four Types of Risk to Consider

• Physical (actions and/or situations that result
  in bodily harm)
• Economic/Financial (loss of privacy that could
  lead to loss of benefits, insurance, or
  employment)
• Social (use of information that might hurt the
  subjects social standing or might cause harm to
  a group of subjects in their community)
• Psychological (causing psychological trauma)

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So what is Benefit

• Something of value in relationship to
  health/welfare
• Benefit can either be individual or for the good
  of the whole

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What about Minimal Risk

• A risk is minimal where the probability and
  magnitude of harm or discomfort anticipated in
  the proposed research are not greater, in and of
  themselves, than those ordinarily encountered in
  daily life or during the performance of routine
  or psychological examinations or tests. (45 CFR
  46.102i)

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Minimal Risk in the current environment

• Is the risk of the protocol more then the risk
  encountered in daily life/usual situation?
• Is standard of care being utilizing in the study
  thus not increasing the risk to any extent?

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http//www.wma.net/e/policy/b3.htmHelsinki
Declaration

• Medical research involving human subjects should
  be conducted only by scientifically qualified
  persons and under the supervision of a clinically
  competent medical person. The responsibility for
  the human subject must always rest with a
  medically qualified person and never rest on the
  subject of the research, even though the subject
  has given consent.
• Every medical research project involving human
  subjects should be preceded by careful assessment
  of predictable risks and burdens in comparison
  with foreseeable benefits to the subject or to
  others. This does not preclude the participation
  of healthy volunteers in medical research. The
  design of all studies should be publicly
  available.
• Physicians should abstain from engaging in
  research projects involving human subjects unless
  they are confident that the risks involved have
  been adequately assessed and can be
  satisfactorily managed. Physicians should cease
  any investigation if the risks are found to
  outweigh the potential benefits or if there is
  conclusive proof of positive and beneficial
  results.
• Medical research involving human subjects should
  only be conducted if the importance of the
  objective outweighs the inherent risks and
  burdens to the subject. This is especially
  important when the human subjects are healthy
  volunteers.

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Minimizing Risks and Avoiding Unreasonable Risks

• Research may not expose subjects to unreasonable
  risk of harm.
• The probability and magnitude of possible harm
  must be reasonable in relation to the anticipated
  direct or direct benefit.
• Identifiable risks that could be practicably
  avoided must be eliminated.
• Sound research design that minimize risks and
  maximize benefits of participation must be used.

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Certificate of Confidentiality

• When research involves the collection of highly
  sensitive information about individually
  identifiable subjects, the IRB may determine that
  special protections are needed to protect the
  subject risk of investigative or judicial
  processes.
• The IRB may require that an investigator secure a
  (DHHS) Certificate of Confidentiality.
• For studies not funded by DHHS, but involves an
  IND or IDE, the Certificate of Confidentiality
  may be requested from the FDA.

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The Certificate of Confidentiality protects
against

• The involuntary release of sensitive information
  about individual subjects for use in
• Federal
• State
• Local
• Criminal, administrative, legislative, or other
  legal proceedings.

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It does not prohibit voluntary disclosure by the
Investigator of

• Child Abuse
• Communicable Disease
• Release to VA, DHHS or FDA for Audit Purposes.

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Who Is Responsible for Minimizing Risks?

• First line Principal Investigator
• (when writing or accepting research protocol)
• The IRB during initial review and thereafter
• The Research Compliance Team
• The Sponsor
• The Monitoring Team
• The Institutional Official

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• What are some potential risks, to participants,
  in the near future?

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• Many thanks to Dr. Belmont for his expert
  contribution to this presentation.