Transcript Slide 1

Research Ethics
Focusing on research involving
human subjects
Session Objectives
 Overview research ethics.
 History of research involving human
subjects.
 Ethical guidelines for research.
 Integrity in research and scholarship.
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Why is human research ethics
review necessary?
Protects research subjects AND
Protects researchers.
Tri-Council Policy Statement (1998)
Memorandum of Understanding (2002)
“… to promote the ethical conduct of research
involving human subjects.”
“. . .will consider funding (or continued funding) only to
individuals and institutions which certify compliance with
this policy.”
Source: Tri-Council Policy Statement
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What do we mean by “ethics?”
Ethic
 “A body of moral principles or values”
Ethical
 “of or pertaining to ethics”
 “in accordance with professional or moral
standards for right conduct or practice”
Ethics
 “a system of moral principles”
 “the right and wrong of certain actions and the
good and bad of such actions often embedded in a
code”
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What is research?
… a systematic investigation to
establish facts, principles or
generalizable knowledge.
Source: Tri-Council Policy Statement
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What is meant by human
research?
 A systematic investigation to establish facts,
principles or generalizable knowledge in which
humans take part as research subjects.
 refers to any project that involves the collection of
specimens, data or information from persons, through
intervention or otherwise.
 included are procedures that have a low degree of
invasiveness (e.g. surveys, interviews, naturalistic
observations, exercise or psychometric testing,
examination of patient records), as well as more
invasive procedures (e.g. blood sampling,
administration of a substance).
Source: Tri-Council Policy Statement
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Why conduct human research?
Research involving humans is
premised on a fundamental
moral commitment to advancing
human welfare, knowledge, and
understanding, and to examining
cultural dynamics.
Tri-Council p. i.4
Source: Tri-Council Policy Statement
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Why research ethics?
 Correct past and prevent new problems and
abuses.
 Human subjects have not always been well
protected.
 Research is big business with enormous amounts
of money involved.
 The future impact of such issues as genetic
engineering, cloning, gene therapy, etc. is not
known.
 Privacy issues for individuals is a growing societal
concern.
 Encourage high quality research accompanied by
high standards of research ethics.
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Milestones
 Nuremberg Code 1947.
 War Trials by the Allies in Nuremberg
 Declaration of Helsinki 1964.
 World Medical Association
 Belmont Report 1979.
 U.S. National Commission for the Protection of
Human Subjects of Biomedical and Behavioral
Research
 TCPS 1998
 NSERC, SSHRC, CIHR
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Nuremburg Code
 The formal elaboration of ethical guidelines
for the conduct of research involving humans
began in the late 1940's.
 In 1946, Nazi physicians were tried at
Nuremberg because of research atrocities
performed on prisoners of war.
 Subsequently, in 1947, the Nazi War Crimes
Tribunal issued the Nuremberg Code, which
was the first internationally recognized code
of research ethics.
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The Nuremberg Code
 Voluntary consent of the participant.
 Results need to benefit society in some way.
 Human experimentation should be based on
animal research results as well as knowledge of
the natural course of events.
 All unnecessary mental or physical harm should
be avoided.
 Researchers should serve as subjects if there is
reason to believe that death or injury may
occur.
[from Trials of War Criminals before the Nuremberg Military
Tribunals under Control Council Law No. 10. Nuremberg,
October 1946–April 1949. Washington, D.C.: U.S. G.P.O,
1949–1953.]
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The Nuremberg Code
 Risk should never exceed the benefits.
 Every precaution should be taken to protect
subjects from harm.
 Only qualified personnel should be allowed to
conduct experiments.
 Subjects must be able to withdraw from a study
at any time.
 The researcher must be ready to terminate the
experiment if it appears that the subjects are
being harmed.
[from Trials of War Criminals before the Nuremberg Military
Tribunals under Control Council Law No. 10. Nuremberg,
October 1946–April 1949. Washington, D.C.: U.S. G.P.O,
1949–1953.]
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Continuing research problems
 Abuses of research subjects came to
public attention in the U.S. between
1953 and 1972.
 This led some people to conclude that
researchers could not be trusted to
conduct studies involving humans.
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Infamous research studies
 Tuskegee Syphilis Study (1932-72)
 Harvard Radiation Tests (1946 -56)
 Willowbrook Study (1963-1966)
 Jewish Chronic Disease Hospital
Study - 1963
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Tuskegee Syphilis Study
(1932-72)
 Nearly 400 black men in Macon County, AL in
1932.
 Originally a treatment/study (mercury rubs).
 Subjects not informed when treatment stopped.
 Became a “Study in Nature’ - Observe natural
history of disease.
 Penicillin available as treatment in 1943.
 Provisions were taken to prevent Tuskegee
subjects from getting penicillin.
 The study was exposed in 1972, the subjects
given treatment by 1973 and the treatment was
extended to the families of the subjects in 1975.
Source: http://darkwing.uoregon.edu/~pmwhite/1
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Harvard Radiation Tests
 From 1946 to 1956, 19 boys who thought they
were participating in a science club were fed
radioactive milk by researchers who wanted to
learn about the digestive system.
 The experiments were performed at the Fernald
State School in Massachusetts. Researchers
from Harvard University and MIT fed radioactive
forms of iron and calcium to the boys,
sometimes in their breakfast milk, to study the
body's ability to digest minerals.
Source: http://darkwing.uoregon.edu/~pmwhite/1
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Willowbrook Study - 1963-1966
 State School for mentally challenged persons in
New York.
 Study natural history of infectious hepatitis.
 Subjects were all children who were deliberately
infected.
 Defended by saying that the vast majority of
them acquired the infection anyway and it was
better for them to be infected under controlled
research conditions.
 School closed to new residents - but study took
new patients - parents only able to place children
there if they participated in study.
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Source: http://darkwing.uoregon.edu/~pmwhite/1
Jewish Chronic Disease
Hospital Study - 1963
 Injection of live cancer cells into chronically ill
patients to develop information on the nature of
the human transplant rejection process.
 Researchers said consent was given orally but
not documented because it was customary to
undertake much more dangerous procedures
without consent forms.
 Patients weren’t told they would receive cancer
cells because it would frighten the patients
unnecessarily.
Source: http://darkwing.uoregon.edu/~pmwhite/1
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Declaration of Helsinki
 Ethical Principles for Medical Research
Involving Human Subjects.
 Medical research is subject to ethical
standards that promote respect for all
human beings and protect their health and
rights.
 Every patient – including those of a control
group, if any – should be assured of the
best proven diagnostic and therapeutic
method.
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Belmont Report
 RESPECT FOR PERSONS: This principle acknowledges
the dignity and freedom of every person. It requires
obtaining informed consent from all potential research
subjects (or their legally authorized representatives).
 BENEFICENCE: This principle requires that
researchers maximize benefits and minimize harms
associated with research. Research-related risks must
be reasonable in light of expected benefits.
 JUSTICE: This principle requires equitable selection
and recruitment and fair treatment of research
subjects.
Source: http://www.rgs.uci.edu/ora/rp/hrpp/1
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TCPS
Tri-Council Policy Statement
The joint policy expresses the
continuing commitment of the three
Councils to the people of Canada, to
promote the ethical conduct of
research involving human subjects.
TCPS i.1
Source: Tri-Council Policy Statement
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Tri-Council Policy
Statement
Act of Parliament Creates Councils
1985
 Medical Research Council (MRC), now
CIHR
 Natural Sciences and Engineering
(NSERC)
 Social Sciences and Humanities (SSHRC)
Start of Joint Initiative 1994
First Tri-Council Draft 1998
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Why Protect Research
Subjects?
… it is they who bear the risks of the
research …
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What are the guiding ethical
principles?
Human Dignity
Free and Informed Consent
Vulnerable Persons
Privacy and Confidentiality
Justice and Inclusiveness
Balancing Harms and Benefits
Minimizing Harm
Maximizing Benefits
Source: Tri-Council Policy Statement
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A Moral Imperative
Respect for Human Dignity
It is unacceptable to treat persons
solely as means (mere objects or
things), because doing so fails to
respect their intrinsic dignity and thus
impoverishes all of humanity.
Tri-Council i.5
Source: Tri-Council Policy Statement
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Source: Seattle Times
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“Uniformed Consent”
“PATIENTS DIED PREMATURELY in two failed clinical trials at
Seattle's Fred Hutchinson Cancer Research Center —
experiments in which the Center and its doctors had a
financial interest. The patients and their families were never
told about those connections, nor were they fully and
properly informed about the risks of the experiments, an
investigation by The Seattle Times has found.
The patients in these trials were ill with cancers that, left
untreated, would almost certainly have killed them. But
many stood a good chance of survival or at least prolonged
life with traditional care. Instead, many actually died from
the experiments — sooner than they would have with no
treatment at all. “
http://seattletimes.nwsource.com/uninformed_consent/
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Free & informed consent
 Free and informed consent derives from
respect we owe to human dignity, for
respecting persons means respecting their
capacity and right to make free and
informed choices.
 It is also a continuing dialogical process: it
starts when prospective subjects are first
approached and ends when their actual
involvement is over.
Source: Tri-Council Policy Statement
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Formal requirements
Research may begin only if the following conditions have been
met:
 Subjects need a comprehensible statement of the
research purpose, the identity of the researcher, the
expected duration and nature of participation, and a
description of research procedures
 Subjects have to be given the assurance that their
participation is totally voluntary and that they have the
right not to participate if they so wish
 free and informed consent has been given and
maintained throughout the subjects’ participation in
the research
Source: Tri-Council Policy Statement
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Freedom of decision
Consent must be voluntary given, without
manipulation, undue influence or coercion
no deprivation
no exercise of control
no authority over prospective subjects
no extortion of information (acting as
informants for the authorities in place)
Source: Tri-Council Policy Statement
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What is the principle of
minimal risk?
 If potential subjects can reasonably be expected
to regard the probability and magnitude of
possible harms implied by participation in the
research to be no greater than those encountered
by the subjects in those aspects of his or her
everyday life that relate to the research,
 then the research can be regarded as within the
range of minimal risk.
Source: Tri-Council Policy Statement
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Dependency relationships
REBs and researchers should be
especially careful when the research is
being conducted in a dependant
relationship setting:
doctor conducting research with his or her
patients
professor conducting research with his or
her students
Source: Tri-Council Policy Statement
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Basic information package
At the commencement of the free
and informed consent process, the
researcher must provide subjects, or
authorized third parties, with a basic
information package appropriate for
the subjects’ cultural settings
Source: Tri-Council Policy Statement
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Privacy & confidentiality
Dignity and autonomy of human
subjects is the ethical basis of respect
for the privacy of research subjects
Privacy is perceived to be an essential
means of protecting and promoting
human dignity
Source: Tri-Council Policy Statement
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Concerns about obtaining
identifiable personal information
 The type of data to be
collected;
 The purpose for which
the data will be used;
 Limits on the use,
disclosure and
retention of the data;
 Appropriate safeguards
for security and
confidentiality;
 Any modes of
observation;
Source: Tri-Council Policy Statement
 Any anticipated secondary
uses of identifiable data from
research;
 Any anticipated linkage of
data gathered in the
research with other data
about subjects, whether
those data are contained in
public or personal records;
 Provisions of confidentiality
of data resulting from the
research.
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Released data
 Researchers should ensure that the data
released does not contain names, initials or
other identifying information.
 While it may be important to preserve certain
types of identifiers (e.g. region of residence),
these should be masked as much as possible
using a standardized protocol before the data
are released for research purposes.
Source: Tri-Council Policy Statement
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Harms and benefits
 Subjects have the right to be given a comprehensible
description of reasonably foreseeable harms and
benefits that may arise from research participation
and should be informed about likely consequences of
non-action
this is especially relevant in the case of therapeutic
research, or research involving invasive
methodologies or research potentially resulting in
physical or psychological harm
Source: Tri-Council Policy Statement
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Minimal risk, human & social
sciences, & biomedical sciences
 Special issues are raised in clinical
research, especially clinical trials, in which
patients suffering from disease participate
in research on interventions undertaken
for purposes of therapy.
 This does not mean that human and social
sciences research do not pose any threat
to the safety and well-being of subjects.
Source: Tri-Council Policy Statement
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Right to withdrawal
They also have to know that they can
withdraw at any time without prejudice to
pre-existing entitlements
A physician should ensure that continued clinical
care is not linked to research participation
Teachers should not recruit subjects from their
classes, or students under their supervision
without REB approval
Source: Tri-Council Policy Statement
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What requires ethics review?
All research that involves human
subjects requires review and approval
by a Research Ethics Board (REB).
All human research undertaken by
members of, or conducted at, RRC
require ethics review by the RRC REB.
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What is a Research Ethics
Board (REB)?
 Ensures that the highest ethical
standards in the conduct of research
involving human participants are
maintained.
 Reviews all proposed research to
ensure meets ethical standards.
Source: Tri-Council Policy Statement
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What is the REB composition?
 REB Composition
 Expertise in relevant sciences (2)
 Expertise in ethics (1)
 Interest in a non-scientific area (1)
 Community Member (1)
 Ad hoc members
 Substitute members
 Institutional Review Boards (IRBs) in U.S.
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REB decisions
 Types
 approved as submitted;
 approved with suggestions for minor changes;
 approved with conditions (that must be met
before final approval is granted);
 deferred, pending receipt of additional
information or major revisions;
 not approved.
 Notice
 To researchers in writing.
 Approvals are for one year only.
 Researchers right to ask for reconsideration.
 Appeals.
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REB authority
 The RRC REB has jurisdiction over all
research involving human participants.
 The REB has the authority to approve,
reject, propose modifications to, or
terminate any proposed or ongoing
research involving human participants
which is conducted within, or by
members of, RRC.
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What are some RRC REB
review guidelines? - 1
 Clear who is conducting the research.
 Risks are minimized.
 Whether the risks are reasonable (balanced) in
relation to the anticipated benefits to the subjects.
 Informed and freely volunteered consent, including
providing for withdrawal from the research.
 Adequate protection of the privacy of the subjects
and the confidentiality of the information /data
being obtained.
 Selection and recruitment of subjects is inclusive
and appropriate in relation to the research.
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What are some RRC REB
review guidelines? - 2
 Purpose of the study is fully outlined to subjects,
or if deception is necessary, there is appropriate
debriefing.
 Research design is appropriate for the nature of
the research.
 Clarify researcher(s) position of power with
subjects.
 Previous REB reviews must be declared &
submitted.
 Methods of dissemination should be disclosed.
 Conflict of interest are disclosed and mechanisms
for handling outlined.
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The opinion of the REB should be
sought whether:
 the research is conducted by faculty,
students or staff, or external researchers;
 the research is conducted in person or
remotely (e.g., by mail, electronic mail,
fax or telephone);
 the information is collected directly from
subjects or from existing records not in
the public domain.
TCPS, Appendix 1.
Source: Tri-Council Policy Statement
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The opinion of the REB should be
sought whether:
 the research is funded or not;
 the funding is internal or external;
 the subjects are from inside or outside
the institution;
 the subjects are paid or unpaid;
 the research is conducted inside or
outside the institution.
TCPS, Appendix 1.
Source: Tri-Council Policy Statement
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The REB should be sought whether:
the research is observational,
experimental, correlational or
descriptive;
a similar project has been approved
elsewhere or not;
the research is a pilot study or a fully
developed project.
TCPS, Appendix 1.
Source: Tri-Council Policy Statement
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Specific inclusion criteria
 Information collected through intervention
or interaction with a living individual(s);
 Identifiable private information about
individuals;
 Information collected through naturalistic
observation of humans,
 Human organs, remains, tissues and body
fluids, cadavers, embryos or fetuses; and/or
 Written or recorded information derived
from individually identifiable human
subjects.
Source: Tri-Council Policy Statement
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Exclusions
 Use of a public database with aggregated data
and /or information already in the public
domain (e.g. autobiographies, biographies or
public archives).
 Naturalistic observation of participants in, for
example, political rallies, demonstrations or
public meetings where it can be expected that
participants are seeking public visibility.
 Preliminary, informal interviews or casual
conversations that are carried out to help
clarify the design of a research project.
 Information gathering procedures in support of
the general administration of the College.
Source: Tri-Council Policy Statement
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More exclusions
 Quality assurances studies, performance
reviews or testing within normal educational
requirements.
 To diagnose problems, identify appropriate
solutions, provide advice for operation
management, or assess performance.
 To collect data primarily designed to affect the
operations of the College through affirming
satisfaction with the status quo or leading to
quality improvements.
 Student in-class research exercises.
Source: Tri-Council Policy Statement
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However . . .
 All research involving human
subjects must adhere to recognized
ethical standards even if REB review
is not required!
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What is a code of ethics for
Researchers?
 Traditionally, codes can be cast in
positive or negative language.
 Expressed in RRC Integrity Policy.
 Example: Research & Planning Code of Ethics at
www.rrc.mb.ca/researchplan
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A Positive View




Do the right thing.
Tell the truth about what your work.
Share your work.
Be critical of your own work and the
work of others.
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Source: http://www.lij.edu/education_and_research/research2001/1
Another approach: Do not
lie, cheat, or steal
A code of ethics can also be
formulated by forbidding certain
actions. Collectively, these actions can
be grouped under Scientific
Misconduct.
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Source: http://www.lij.edu/education_and_research/research2001/1
Why have an integrity in
research & scholarship policy?
 To promote and advance a high standard of
integrity in research and scholarship
involving:
 careful supervision of research, including that
conducted by students;
 competent use of methods;
 adherence to ethical standards of discipline;
and
 the refusal to engage in or to condone instances
of fraud or misconduct.
 Required by external funding agencies.
 Define misconduct.
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What is scientific
misconduct?
"...fabrication, falsification, plagiarism,
or other practices that seriously
deviate from those that are commonly
accepted in the scientific community
for proposing, conducting or reporting
research."
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Source: http://www.lij.edu/education_and_research/research2001/1
Definitions
fabrication: "making up data or
results,"
falsification: "changing data or
results,"
plagiarism: "using the ideas or words
of another person without giving
appropriate credit."
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Source: http://www.lij.edu/education_and_research/research2001/1
What is misconduct in
research? - 2
 Failure to acknowledge or recognize the
contribution of others.
 Use of material in violation of the Copyright
Act.
 Abuse of supervisory power
 Financial misconduct
 Failure to comply with policies for the
protection of researchers, human
participants, or the health and safety of the
public, or for the welfare of laboratory animals.
 Failure to reveal any material conflict of
interest,.
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Role of REB
 REBs take into account national and,
when appropriate, international ethical
standards of research on a protocol-byprotocol basis.
 Protecting human research subjects is
their primary responsibility.
 Protection of the rights and welfare of
research subjects is a high priority
worldwide.
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Conclusion- balance of
ethics and science
 Balance interest in advancing scientific
knowledge with a mandate to protect
the rights and welfare of people.
 Ethics protects research subjects and
researchers.
 Sound ethics and good science are
compatible.
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If you want to know more …
Tri-Council Policy
Statement Tutorial is
available at:
http://www.pre.ethics.gc.ca
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