Research Ethics 101: The
Ethical Conduct of
Research
Author: Charles Weijer
Rotman Institute of Philosophy
Western University, Canada
Date: March 20, 2012
Conflict of interest disclosure
• I do not hold any research grants funded by
industry or serve on any advisory committees of
a pharmaceutical company
• I have no other relevant financial relationships
with members of the pharmaceutical industry or
medical supply companies.
2
Objectives
• At the end of the session, participants will be
able to:
1. Explain the historical imperative for protections
of human research participants;
2. Define the four ethical principles; and,
3. Apply the principles to their own research
studies.
3
Why is it important?
• Health research improves our understanding of
disease, and informs practices that improve
health
• Both knowledge and health are important public
goods
• Health research depends on the voluntarism of
research subjects
• State has an obligation to protect and promote
the liberty and welfare interests of human
research subjects
• Promulgates regulations and guidelines
• Creates oversight structures, e.g., research ethics board
(REB)
4
Why is it important?
• Health research has a lengthy history of abuses
• The interests of research subjects have all too
often been sacrificed to scientific ends or the
ends of the state
• Well known instances
• Nazi hypothermia experiments
• Tuskegee syphilis study
• Mind-control research at the Allan Memorial in Montreal
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Tuskegee syphilis study
• Longest running
study in the U.S.
PHS; ran from 1932
to 1972
• Studied the natural
history of syphilis in
400 African American
males
• Motivated by the
concern that syphilis
might be less harmful
in this group
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Tuskegee syphilis study
• Syphilis untreated, even
when penicillin became
available in the late
1940s
• Letters “not to treat”
were inserted in army
service records
• Told that nontherapeutic procedures
were “special
treatment[s]”
7
“Special treatment”
A 1933 photo of a subject undergoing a lumbar
puncture (spinal tap). (Archives of the Center for
Disease Control, Tuskegee Study Files.)
8
U.S. Senate inquiry
Senator Kennedy: What were the shots for, to cure the bad blood?
Mr. Pollard: Bad blood, as far as I know of.
Senator Kennedy: Did you think they were curing bad blood?
Mr. Pollard: I didn't know. I just attended the clinic.
Senator Kennedy: They told you to keep coming back and you did?
Mr. Pollard: When they got through giving the shots, yes. Then
they gave us that spinal puncture.
Senator Kennedy: Did they tell you why they were giving a spinal
puncture?
Mr. Pollard: No.
Senator Kennedy: Did you think it was because they were trying to
help you?
Mr. Pollard: To help me, yes.
Senator Kennedy: You wanted some help?
Mr. Pollard: That is right. They said I had bad blood and they was
working on it.
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Belmont Report
• National Commission for the Protection of Human
Subjects of Biomedical and Behavioral Research
(1974-1978)
• Charged with defining ethical principles to guide the
conduct of research
• Belmont Report (1978)
• Respect for persons
• Beneficence
• Justice
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Regulation
• World Medical Association Declaration of Helsinki
(1964, rev. 2008) www.wma.net
• Council for International Organizations of Medical
Sciences (CIOMS) International Ethical Guidelines
for Biomedical Research Involving Human Subjects
(2002) www.cioms.ch
• International Conference on Harmonization (ICH)
Good Clinical Practice Guidelines www.ich.org
11
Tri-Council Policy Statement 2
• Joint policy of CIHR,
NSERC, SSHRC
• Version 1, 1998; revised
in 2010
• Applies to all research
funded by Councils or
conducted at an
institution that receives
Council funding
• Available at
www.pre.ethics.gc.ca
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The Research Ethics Board (REB)
• Is an arm of the state whose mandate is to ensure
that the liberty and welfare interests of human
research subjects are protected and promoted
• Ensures that proposed research projects comply
with relevant regulations, guidelines, and ethical
principles
• Unlike clinical practice, clinical research is subject
to up front review because research exposes people
to risk (at least in part) for the benefit of others
• Is composed of researchers, ethicist, lawyer,
community representative (TCPS 6.4)
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What is research?
• Defined as an “undertaking intended to extend
knowledge through a disciplined inquiry or
systematic investigation” (TCPS 2.1)
• It is not research if:
• It isn’t disciplined inquiry or systematic
investigation; or,
• It doesn’t seek to extend knowledge.
• Quality assurance initiatives — systematic
investigations to inform change in only local
practice or policy — are not research and are not
subject to REB review. (TCPS 2.5)
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What research requires REB review?
TCPS 2.1:
“The following requires ethics review and approval
by an REB before the research commences:
a) research involving living human participants;
b) research involving human biological materials,
as well as human embryos, fetuses, fetal
tissue, reproductive materials and stem cells.
This applies to materials derived from living
and deceased individuals.”
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Qualitative research
TCPS 10.1:
“Researchers shall submit their research proposals,
including proposals for pilot studies, for REB review
and approval of its ethical acceptability prior to the
start of recruitment of participants, or access to
data. Subject to the exceptions in Article 10.5, REB
review is not required for the initial exploratory
phase (often involving contact with individuals or
communities) intended to discuss the feasibility of
the research, establish research partnerships, or
the design of a research proposal (see Article
6.11).”
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Ethical principles
• Respect for persons
• Obligation to take seriously the choices of autonomous
subjects and they have an obligation to protect those
who cannot decide for themselves.
• Beneficence
• Obligation to protect human research subjects from harm
and where possible promote their good.
• Justice
• Benefits and burdens of research participation ought to
be distributed equitably
• Respect for communities
• Obligation to protect and promote the interests of
communities in research
17
Ethical principles and rules
Ethical principle
Respect for persons
Ethical rule
Obtain the informed consent of prospective research
subjects
Protect the confidentiality of private information
Beneficence
Therapeutic procedures must satisfy clinical
equipoise
Risks of non-therapeutic procedures must be (1)
minimized and (2) reasonable in relation to
knowledge to be gained
Justice
Subject selection procedures must be fair
Compensate subjects harmed as a result of research
participation
Respect for communities
Respect communal values, protect and empower
social institutions
Where applicable, abide by the decisions of
legitimate communal authority
18
Informed consent
• General presumption that informed consent must be
obtained from research subjects (TCPS 3.1-3.5)
• Additional protections for those who cannot provide
informed consent (TCPS 3.9, 4.6)
• Inclusion must be necessary to answering the study
hypothesis
• Consent from a surrogate decision maker
• Threshold for non-therapeutic risks to which they may
be exposed (minimal risk)
19
Waiver of consent (TCPS 3.7)
• The research involves no more than minimal risk to
the participants;
• The lack of the participant’s consent is unlikely to
adversely affect the welfare of the participant;
• It is impossible or impracticable to carry out the
research and to answer the research question
properly, given the research design, if the prior
consent of the participant is required;
20
Waiver of consent (TCPS 3.7)
Con’t
• whenever possible and appropriate, after
participation…participants will be debriefed; and
• the research does not involve a therapeutic
intervention, or other clinical or diagnostic
interventions.
21
Confidentiality
• Researchers are obliged to take steps to protect the
confidentiality of private health information (TCPS
5.1)
• REB has an obligation to review confidentiality
procedures for adequacy (TCPS 5.3)
• Steps taken to protect the confidentiality of private
health information ought to be disclosed in the
informed consent (TCPS 5.2)
22
Secondary use of data
• REB review is not required for research that involves
secondary use of anonymous data or samples (TCPS
2.4)
• REB review is required if the data or samples are
identifiable, or if the process of data linkage
generates identifiable information
• Informed consent may not be required for secondary
use of data or samples provided that:
• The identifiable data is essential to the research;
• Appropriate safeguards for confidentiality are in place; and,
• It would be impossible or impracticable to seek individual
consent (TCPS 5.5).
23
Qualitative research
• “The requirement for consent and the protection of
privacy and confidentiality do not change with the
nature of the research.” (TCPS p.138)
• Article 10.3: “In research involving observation in
natural environments or virtual settings where people
have a reasonable or limited expectation of privacy,
the researcher shall explain the need for an
exception to the general requirement for consent.”
• Informed consent is required to disclose the identity
of human research subjects (TCPS 10.4)
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Ethical principles and rules
Ethical principle
Respect for persons
Ethical rule
Obtain the informed consent of prospective research
subjects
Protect the confidentiality of private information
Beneficence
Therapeutic procedures must satisfy clinical
equipoise
Risks of non-therapeutic procedures must be (1)
minimized and (2) reasonable in relation to
knowledge to be gained
Justice
Subject selection procedures must be fair
Compensate subjects harmed as a result of research
participation
Respect for communities
Respect communal values, protect and empower
social institutions
Where applicable, abide by the decisions of
legitimate communal authority
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Benefit-harm analysis
• The REB must “assesses the ethical acceptability of
the research through consideration of the foreseeable
risks, the potential benefits and the ethical
implications of the research, both at the stage of the
initial review and throughout the life of the project”
(TCPS p.22)
• Risks that are considered:
• physical;
• psychological;
• social; or,
• economic
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Benefit-harm analysis
• We must distinguish between procedures
administered with therapeutic warrant and those
administered without such warrant and purely to
answer the scientific question
• Therapeutic procedures: potential benefit to
subject
• Non-therapeutic procedures: potential benefit to
society
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Therapeutic procedures
• A state of clinical equipoise must exist at the start of
a study (TCPS p. 148)
• The various therapeutic procedures within the study
must be consistent with competent medical care
• At the start of the trial there must exist a state of
honest, professional disagreement in the community
of expert practitioners as to the preferred treatment
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Nontherapeutic procedures
• Two requirements:
• Risks to subjects are minimized consistent with sound
scientific design
• Risks reasonable in relation to knowledge to be gained
• If the study involves a vulnerable population, the
risks of nontherapeutic procedures must be no
more than:
• Minimal risk (Canada) (TCPS 3.9d)“probability and magnitude
of possible harms implied by participation in the research is no
greater than those encountered by participants in those aspects of
their everyday life that relate to the research” (TCPS p. 23)
• Minor increase above minimal risk (US)
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Benefit-harm analysis
Protocol
Therapeutic
procedures
Distinguish therapeutic
and nontherapeutic
procedures
Nontherapeutic
procedures
Clinical equipoise
exists
Risks minimized
consistent with sound
scientific design
Consistent with
competent care
Risks reasonable in
relation to knowledge to
be gained
Risks reasonable in
relation to potential
benefits to subjects
No more than
minor increase over
minimal risk
Yes
Both therapeutic
and nontherapeutic
procedures pass
Yes
Acceptable
Vulnerable
population?
No
No
Unacceptable
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Ethical principles and rules
Ethical principle
Respect for persons
Ethical rule
Obtain the informed consent of prospective research
subjects
Protect the confidentiality of private information
Beneficence
Therapeutic procedures must satisfy clinical
equipoise
Risks of non-therapeutic procedures must be (1)
minimized and (2) reasonable in relation to
knowledge to be gained
Justice
Subject selection procedures must be fair
Compensate subjects harmed as a result of research
participation
Respect for communities
Respect communal values, protect and empower
social institutions
Where applicable, abide by the decisions of
legitimate communal authority
31
Selection of subjects
• TCPS Section 4: Fairness and Equity in Research
Participation
• Undue burdens (TCPS 4.7):
• Those who will not share in study benefits
• Groups exposed to repeated study may be unduly
burdened by research participation
• Access to benefits:
• Exclusion of groups may lead to systematic gaps in
medical knowledge
• Children, women, elderly, members of minority groups
may not be excluded without careful justification (TCPS
4.2-4.5)
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Research-related injury
• Researchers
have
an ethical
torisk of
“Harm, disability
or death
suffered obligation
by a subject at
provide and
compensation
or treatment
forinjury is (1)
biomedical
behavioral research…where
such
research-related
injuries
proximately
caused by such
research, and (2) on balance exceeds
that reasonably associated with such illness from which the
• In the consent process, subjects must be
subject may be suffering, as well as with treatment usually
informed of the availability of compensation
associated with such illness at the time the subject began
for injury (TCPS 3.2)
participation in the research.”
(HEW Task Force, 1977)
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Ethical principles and rules
Ethical principle
Respect for persons
Ethical rule
Obtain the informed consent of prospective research
subjects
Protect the confidentiality of private information
Beneficence
Therapeutic procedures must satisfy clinical equipoise
Risks of non-therapeutic procedures must be (1)
minimized and (2) reasonable in relation to
knowledge to be gained
Justice
Subject selection procedures must be fair
Compensate subjects harmed as a result of research
participation
Respect for communities
Respect communal values, protect and empower
social institutions
Where applicable, abide by the decisions of legitimate
communal authority
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Communities
Recognizing the heterogeneity of communities,
researchers may in particular instances have
obligations to:
• Engage the community in
the development of the
study
(TCPS 9.1, 9.2)
• Disclose information to the
community and, where
appropriate, seek
community consent
(TCPS 9.3)
• Negotiate access to and
storage of data and
samples
(TCPS 9.16, 9.19, 9.20)
• Involve the community in
the dissemination and
publication of study
findings
(TCPS 9.17)
• Involve the community in
the conduct of the study
(TCPS 9.12, 9.13, 9.14)
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Ethical principles and rules
Ethical principle
Respect for persons
Ethical rule
Obtain the informed consent of prospective research
subjects
Protect the confidentiality of private information
Beneficence
Therapeutic procedures must satisfy clinical equipoise
Risks of non-therapeutic procedures must be (1)
minimized and (2) reasonable in relation to knowledge
to be gained
Justice
Subject selection procedures must be fair
Compensate subjects harmed as a result of research
participation
Respect for communities
Respect communal values, protect and empower social
institutions
Where applicable, abide by the decisions of legitimate
communal authority
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Online learning
• RCPSC Bioethics Education Project
(click on “bioethics modules” after sign in)
• Curriculum with 5 primers on ethics, 5 executive summaries,
46 case discussions, and 5 self-assessment modules
• Primer on “Research Ethics” by Andrew McRae
(Calgary)
• Research ethics cases:
•
•
•
•
•
•
Research Ethics Review
Consent to Research Participation
Physicians' Obligations to Patients in Clinical Research
Research Involving Vulnerable Populations
Research Involving Children
Informing Study Participants of Research Results
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