Human Subject
Research Ethics
Colleen M. Gallagher, PhD, FACHE
Chief & Executive Director, Section of Integrated
Ethics
Associate Professor, Department of Critical Care
Definition of Research
Research is designated as an
activity that permits
conclusions to be drawn, and
develops or contributes to
generalizable knowledge.
Research: Code of Federal
Regulation(CFR)Definition
• Research means a systematic
investigation, including research
development, testing and evaluation,
designed to develop or contribute to
generalizable knowledge.
• Activities which meet this definition
constitute research for purposes of this
policy, whether or not they are
conducted or supported under a
program which is considered research
for other purposes. For example, some
demonstration and service programs
may include research activities.
Human Subjects
• Human subject means a living
individual about whom an
investigator (whether professional or
student) conducting research obtains
• (1) Data through intervention or
interaction with the individual, or
(2) Identifiable private information.
Clinical Care and Clinical
Research
• Clinical care based on individual
patient well being and “best interests”
• Clinical research based on developing
new knowledge not individual patient
well being and “best interests”
Human Subject Research
Ethical Guidelines
• 1947 Nuremburg Code
• 1964 Declaration of Helsinki
(amended most recently 2004)
• 1979 The Belmont Report
• -Respect for persons,
• beneficence, non-maleficence,
• justice
• 1982 International GuidelinesInternational Organization of Medical
Sciences (amended 2004)
Belmont Report Principles
Three basic principles
1.Respect for Persons (Autonomy):
This principle acknowledges the dignity and
freedom of every person.
It requires obtaining informed consent from
research subjects (or their legally authorized
representatives)
Belmont Report Principles
Beneficence and Nonmaleficence:
This principle requires that
researchers maximize benefits and
minimize harms associated with
research. Research-related risks must
be reasonable in light of expected
benefits.
Belmont Report Principles
• Non-Maleficence
• One ought not to inflict evil or harm
• Generally the “do nots”
• Do not kill
• Do not injure
• Do not violate
• Do not cause pain and suffering
• Do not cause offense
Belmont Report Principles
Justice:
This principle requires equitable
selection, recruitment and fair
treatment of research subjects.
What makes clinical research
ethical?
• Social or scientific value
• Scientific validity
• Fair subject selection
• Favorable risk - benefit ratio
• Independent review has been
conducted
• Informed consent process
• Respect for potential and enrolled
subjects
Investigators Responsibilities
• Follow the protocol
• Submit research to the IRB and have
approval prior to initiation of
research
• Comply with IRB policies, decisions,
conditions, and requirements
• Obtain and document informed
consent
• Provide a copy of the IRB approved
consent form to each subject
Investigators Responsibilities
• Ensure that assent is obtained from
research participants who are minors
(18 years of age and under)
• Report progress of approved
research annually
• Submit any modifications to a
protocol or consent form
• Maintain a protocol file
Special Considerations
Vulnerability
• “When some or all of the subjects are
likely to be vulnerable to coercion or
undue influence, such as children,
prisoners, pregnant women, mentally
disabled persons, or economically or
educationally disadvantaged person,
additional safeguards have been
included in the study to protect the
rights and welfare of these subjects”
(45 CFR 46 111b)
Types of Vulnerability
1.
2.
3.
4.
5.
6.
7.
Incapacitational
Juridic
Deferential
Social
Situational
Medical
Allocational
Incapacitational
•Lacks the capacity to deliberate about
and decide whether to participate in
the study.
• Pediatric patients
• Mentally/cognitively impaired
Juridic
•Liability to the authority of others
who may have an independent interest
in participation in the study.
• Minor – parent
• Adult child – parent in some cultures
• Wife – husband in some cultures
• Elderly parent – adult child
Deferential
•Given to patterns of deferential
behavior that may mask an underlying
unwillingness to participate.
• Child to parent
• Female to males
• Young to elders
• Deference to all doctors
Social
•Belongs to a group whose rights and
interests have been socially disvalued.
• Racial/ethnic minority
• Women
• Disabled
Situational
•In a situation in which medical
exigency prevents the education and
deliberation needed to decide whether
to participate.
• A number cancer patients –
especially leukmias and CNS tumors
Medical
•Selected, in part, because of the
presence of a serious health-related
condition for which there is no
satisfactory remedies.
• Many relapsed/refractory cancer
patients
Allocational
• Lacking in subjectively important
social goods that will be provided
as a consequence of participation
in research.
Additional Research Risks
•
•
Pregnant women and fetuses
Research carries additional or
special risks
• Gestating women’s bodies may
have special needs or respond
differently.
• Potential conflict between
woman’s health needs and the
fetus – what is a risk or benefit
for one may not be for the other
Additional Research Risks
•
•
•
•
Subpart B
Require more preliminary studies
(higher burden to do research)
(46.204a)
Any risk is the least possible for
achieving objectives of the research
(46.204c)
Greater than minimal risk to fetus has
to be justified by prospect of direct
benefit to pregnant woman or fetus,
and by the fact that there is no other
means to obtain that knowledge.
(46.204d)
Targeting for Wrong Reasons
•
Being asked to take participate in research
because it is expedient (cheaper, more
convenient, less administratively
burdensome) and not for scientific
reasons (condition being studied affects
this group more often)
•
Think about Havasupai situation as an
example.
•
Subject Selection Fairness (45 CFR
46.111a.3)
Targeting for Wrong Reasons
•
•
Subpart C (prisoners)
Research has to be about one of the
following:
• Causes, effects, etc, of criminal
behavior
• Prison structures
• Conditions particularly affect
prisoners as a class
• Practices that have intent of
improving health or well-being of
prisoners (46.306a)
IRB and Vulnerability
•
•
Recognize different types of
vulnerability
Use different strategies to address
different vulnerabilities.
•
Research protocol design
• Empowering subjects in
the research process
Questions
• Ask for Research Ethics Consultation
• 713-792-8775
• contact one of the ethicists using the
paging system 404-2863