Human Research Protection Program 101

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Human Research Protection Program 101

• July 19-20, 2007
• Milwaukee, WI

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Consideration of Risks and Benefits at Initial
Review
Presented by John C. Hudson MS
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A story of two investigators
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Consideration of Risks and Benefits

• Fulfill regulatory requirements set forth in
  Common Rule (VA 38 CFR 16.111 DHHS 45 CFR
  46.111)
• And as described in 1200.5
• (Para.7 IRB Responsibilities and
  Authority)
• More than just regs
• CONSIDERATION OF RISKS TO SUBJECTS AND POSSIBLE
  BENEFITS OF RESULTS IS CENTRAL TO THE REVIEW OF
  HUMAN SUBJECTS RESEARCH

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Why Consider Risks Benefits

• The main charge of an IRB is their responsibility
  to protect the RIGHTS and WELFARE of human
  subjects in research
• Practical aspect in addition to the
  ethical/moral responsibilities there is a legal
  aspect ? NOT protecting the rights and welfare of
  human subjects invites bad press, lawsuit, even
  the shutting down of an institution
• Point to consider Weighing of Risks and Benefits
  is WHY we have IRB review

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• BUT WHAT DO WE MEAN BY THE RISKS AND BENEFITS OF
  HUMAN SUBJECTS RESEARCH?

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Risk What is it?

• The probability of harm or injury occurring as a
  result of participation in a research study
• Prediction of some future occurrence of harm
• Consideration of probabilities what has happened
  before?

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Risks Types of Risk

• Physical
• Psychological
• Social
• Economic
• Legal

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Risks Types of Risk

• Physical
• Psychological
• Emotional
• Loss of dignity
• Embarrassment
• Social
• Loss of confidentiality
• Loss of social status
• Threat to privacy
• Harassment
• Economic
• Threat to employment
• Insurability and insurance costs

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Social and Psychological Risks are REAL Risks

• Social and Psychological risks are TIME and
  SITUATION specific
• Pregnancy in minors v. in adults
• Known Alzheimers at less risk than some one not
  yet identified
• Offspring at risk if genetically-linked
• Social and Psychological risks are subjective

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Benefit What is it?

• A valued or desired outcome an advantage
• The probability of hoped for benefits

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Benefit Hoped for benefits?

• Two Major Categories
• Benefits to participants
• Benefits to society
• Research may have
• Therapeutic intent (intend to affect a medical
  condition or understand that condition)
• Nontherapeutic (increase knowledge
• basic research)

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Risk/Benefit Analysis

• Risks and benefits are not parallel ideas
• Risks often individual, immediate, measurable
• Benefit often elusive, future, potential
• Need to maintain a favorable balance

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What the Codes and Regulations Say

• The degree of risk to be taken should never
  exceed that determined by the humanitarian
  importance of the problem to be solved by the
  experiment (Nuremberg 6)
• Biomedical research involving human subjects
  cannot legitimately be carried out unless the
  importance of the objective is in proportion to
  the inherent risk to the subject (Helsinki I.4)
• Risks to the subjects must be reasonable in
  relation to anticipated benefits, if any, to
  subjects, and the importance of the knowledge
  that may reasonably be expected to result (45 CFR
  46.111a)

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Belmont Report its all about risk

• Three basic ethical principles in the Belmont
  Report guide the conduct of research with human
  subjects
• Respect for Persons Includes honoring the
  privacy of individuals and maintaining their
  confidentiality.
• Beneficence Should maximize potential benefits
  to subjects minimize potential risks. If any
  risks may result from participation then there
  must be benefits to the subject, to humanity, or
  to society in general.
• Justice Subjects selected fairly and that the
  risks and benefits of research are distributed
  equitably. Precautions to not select subjects
  simply because of the subjects easy
  availability, their compromised position, or
  because of racial, sexual, economic, or cultural
  biases in society.

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Identifying risks and benefits?

• NO ONE can be objective about their own work
• Underestimate risks
• Overestimate benefits
• IRB acts as objective referee

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The Role of the IRB

• Review potential risks, discomforts, hazards, or
  inconveniences of protocol
• Probability, magnitude, duration, reversibility
  of risks
• Separate risks of research from standard of care
  risks
• e.g. Risks of surgery already scheduled
• Give special consideration to risks for research
  involving vulnerable populations
• Children, mentally impaired, prisoners, others

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The Role of the IRB (cont.)

• Consider hoped for benefits
• Benefits can take the form of therapy, education,
  information, resources or empowerment
• Benefits can be directed at participants, their
  community, society, medical knowledge, medical
  technology
• Consider if risks reasonable in relation to
  possible benefits
• Balancing potential risks to participant/others
• against possible benefits to participant/society

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The IRB Balancing potential risks

• No benefit requires no risk to participants
• Little benefit requires low risk
• High risk studies require showing of significant
  benefit to participants
• To determine balance consider type of risk
• Physical, psychological, social, economic

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Special Categories of Risk
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Minimal Risk

• Risk level is determined by the IRB
• 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)
• ? For research to be exempt from IRB review
  it MUST be minimal risk

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Significant/Non-significant Risk

• FDA Device studies rules Significant risk is
  when there is a potential serious risk to health
  of subject and the device is
• An implant
• Used in supporting/sustaining life
• Important to diagnose, mitigate, or treat disease
  or prevent impairment of human health
• Otherwise Non-significant

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Worth keeping in mind

• IRB review of research is NOT an adversarial
  enterprise
• With proper review, consideration of regulations,
  and inclusion of safeguards human subjects
  research relatively safe to participants
• Human subjects research can be beneficial to
  improving health care at large and/or basic
  knowledge

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All share the same mission

• The IRB should be working with investigators as
  part of a cooperative Research Enterprise whose
  goal is to advance society and its health
• Consideration of Risks and Benefits is part of
  the overall review of Hum Sub research focusing
  on subject safety and welfare

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Consideration of Risks and Benefits
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QUESTIONS