Transcript Institutional Review Board 03 Retreat September 26, 2000

A History of Human Research
Protections and Institutional
Review Boards
Roger L. Bertholf, Ph.D.
Associate Professor of Pathology
Chair, University of Florida IRB-03
The Nuremberg Trials
• The International Military Tribunal (1945)
• The Doctors Trial (1946)
• The Nuremberg Code (August, 1947)
The Nuremberg Code
• Established necessity of informed
consent
• Introduced concept of beneficence
• Introduced the notion of proportionality
between risk and benefit
The Declaration of Helsinki
• Adopted by the World Medical Association in
1964
• Provided guidelines for the conduct of human
subjects research
–
–
–
–
Institutional Review Boards
“generally accepted scientific principles”
Distinction between clinical and basic research
Placebo controversy
The Tuskegee Syphilis Study
• PHS initiated syphilis treatment program in
1928
• Discovered 35 – 40% infection rate in Macon
County, AL
• Revised study to observation only
• Enlisted help of the Tuskegee Institute
• Terminated in 1972
The Belmont Report
• Drafted by the National Commission for the
Protection of Human Subjects in Biomedical
and Behavioral Research
• Final version adopted in 1979
• Three sections:
– Clinical practice vs. research
– Three guiding principles of ethical research
– Application of the three principles
Clinical practice vs. research
• What is the purpose of the activity?
• Are results generalizable?
• Example
Three Guiding Principles of
Ethical Research
• Respect for Individuals
• Beneficence
• Justice
Respect for Individuals
• Individuals act as autonomous agents
An autonomous person is an individual capable of
deliberation about personal goals and of acting
under the direction of such deliberation. To respect
autonomy is to give weight to autonomous persons’
considered opinions and choices while refraining
from obstructing their actions unless they are clearly
detrimental to others. To show lack of respect for an
autonomous agent is to repudiate that person’s
considered judgments, to deny an individual the
freedom to act on those considered judgments, or to
withhold information necessary to make a
considered judgment, when there are no compelling
reasons to do so.
Respect for Individuals
• Individuals act as autonomous agents
• Individuals who are not capable of acting
as autonomous agents are entitled to
special protections
– Minors
– Mentally incapacitated persons
– Prisoners
Beneficence
• Guided by two basic principles:
– Do no harm
– Maximize benefits and minimize potential harms
• Risks should be in proportion to potential
benefits
• Research design should ensure valid results
Justice
• Benefits and risks of human research
should be fairly distributed
• How do you select human research
subjects?
– Societal allocation of burdens and benefits
– Equality, need, contribution, effort, merit
• Social vs. individual justice
The Informed Consent
• Complete disclosure of all procedures, any
foreseeable risks, and any reasonably
anticipated benefits
• Informed consent can be waived only if:
– The risks are no greater than minimal
– The research cannot be practically conducted if
consent is required
– Subjects are debriefed, when appropriate
The Informed Consent
• Proxy consent
• Intentional/unintentional coercion
• Information must be presented in a
comprehensible manner
Assessment of Risk/Benefits
• Research involving brutal or inhumane treatment
is never acceptable
• Risks should be reduced to only those necessary
to achieve the objective
• If there is risk of serious impairment, there must
be extraordinary justification
• If vulnerable populations are used, there must be
a specific reason for doing so
• Relevant risks must be included in the informed
consent
Federal Regulations
• 45 CFR 46
– The Common Rule (Part A)
– Subparts B, C, and D
• 21 CFR 50 and 56
– 50 includes rules for clinical trials
– 56 describes IRB responsibilities
The Multiple Project Assurance
• Any institution conducting federally
funded (or regulated) research must
provide the OHRP with a legally binding
assurance that human research subjects
are protected from unnecessary risk.
– Single or Multiple
– MPAs are usually approved for 5 years
The University of Florida MPA
• Provides for 4 IRBs: 01-04 (WIRB)
• Stipulates that all research at UF
involving human subjects will be
conducted in accordance with federal
guidelines
Components of the UF MPA
•
Institution is guided by the ethical principles
in the The Belmont Report
Specifies that IRBs will consider:
•
–
–
–
–
the risks to the subjects,
the anticipated benefits to the subjects and others,
the importance of the knowledge that may
reasonably be expected to result, and
the informed consent process to be employed.
Applicability of the UF MPA
•
The UF MPA applies if any of the following
conditions are met:
–
–
–
–
the research is sponsored by this institution, or
the research is conducted by or under the direction of any
employee or agent of this institution in connection with his
or her institutional responsibilities, or
the research is conducted by or under the direction of any
employee or agent of this institution using any property or
facility of this institution, or
the research involves the use of this institution's non-public
information to identify or contact human research subjects
or prospective subjects.
IRB responsibilities
•
•
The IRB-03 is administratively responsible to the
President of this institution, who has delegated the
responsibility to this institution’s Vice President for
Research. (Dr. Win Phillips)
This institution's IRBs have effective knowledge of
subject populations, institutional constraints,
differing legal requirements, and other factors which
can foreseeably contribute to a determination of
risks and benefits to subjects . . .
The Office for Human
Research Protections (OHRP)
DHHS
(Formerly DHEW)
Tommy Thompson, Sec'y
Office of the Secretary
OHRP
Greg Koski, MD
FDA
21 CFR 50, 56
NIH
45 CFR 46
OPRR
(until June, 2000)