Transcript Research Ethics II

Ethical Legal/Issues in Human
Subject Research II
ISD II – Infectious Diseases
Barbara Barrowman
Andrew Latus
March 7, 2003
Outline
 Second of a two-part consideration of legal and
ethical issues related to human subject research.
 In the first session (during the GI course), we
considered the following issues:
 What is research?
 Rationale for research ethics review
 Ethical/legal/regulatory framework for human
subject research in Canada
Outline (cont.)
 We also identified a number of major ethical/legal
issues in human subject research:
1.
2.
3.
4.
5.
6.
Scope of acceptable research
Conflicts of interest
Consent - informed, voluntary
Confidentiality, access to information
Children, mentally incompetent individuals
Justice in recruitment of subjects
 Covered # 2 and 3 in the last session.
 Today, we will cover the other issues, with an
emphasis on #1 and 4.
The Tuskegee Syphilis Experiment
 Clear example of ethically unacceptable research, at
least by present standards
 Some problems:
– Lack of informed consent due to deception
 Study was presented as treatment
 Treatments for syphilis were available
– Conflict of interest caused profound failure in duty to care
– Injustice in selection of subject population
– Unacceptable form of research
 Clearly illustrates need for a focus on research ethics
Some History of Research Ethics
 Early codes of medical ethics tended to treat
research as part of overall code of medical ethics
– Today, treated as a distinct area
 Thomas Percival
– 1803 - first code of medical ethics to include requirements
concerning research?
– The use of experimental techniques on patients should be
“scrupulously and conscientiously governed by sound
reason” and undertaken only after consulting with other
physicians
– No mention of seeking the consent of the subject
Paternalistic Research Ethics
 “It is our duty and our right to perform an
experiment on a man whenever it can save
his life, cure him or gain him some personal
benefit. … So, among the experiments that
might be tried on man, those that can only
harm are forbidden. Those that are innocent
are permissible, and those that may do good
are obligatory.”
– 1865 - Claude Bernard, an influential French
physiologist,
William Beaumont - Research Ethics
Pioneer?
 Some credit Beaumont with the “oldest …
code” specifically focussed on human
experimentation (1833):
– “5. The voluntary consent of the subject is
necessary…
– “6. The experiment is to be discontinued when it
causes distress to the subject…
– 7. The project must be abandoned when the
subject becomes dissatisfied.”
 Some dispute about whether code actually
existed.
Policy vs. Practice
 Ironically, some of the earliest and clearest
pronouncements on the importance of consent in
medical research are to be found in early 20th century
Germany
– Vaccination trials without consent on poor and vulnerable
people (abandoned children, prostitutes) led to research
regulations in Prussia in 1900
– A 1931 directive from the German Reich Minister of the
Interior forbids “innovative therapy” unless the “subject or his
legal representative has unambiguously consented to the
procedure in the light of relevant information provided in
advance”
The Nuremberg Code
 The modern era in research ethics begins
with the Nuremberg Code (1947)
 Produced as part of the “Doctors’ Trial,” part
of the post-W.W.II war crimes tribunal
– Response to research atrocities
– Deliberate infection with malaria, smallpox,
cholera
– Sexual sterilization experiments
– Cold temperature experiments
From the Nuremberg Code
 “The voluntary consent of the human subject
is absolutely essential.”
– “This means that the person involved should have legal
capacity to give consent; should be so situated as to be able
to exercise free power of choice … and should have
sufficient knowledge and comprehension of the elements of
the subject matter involved as to enable him to make an
understanding and enlightened decision. This latter element
requires that before the acceptance of an affirmative
decision by the experimental subject there should be known
to him the nature, duration and purpose of the experiment;
the methods and means by which it is to be conducted; all
inconveniences and hazards reasonably to be expected; and
the effects upon his health or person which may possibly
come from his participation in the experiment.”
Not the End of Atrocities
 Unfortunately, as already noted policy is one thing
and practice another. Some examples:
–
–
–
–
Tuskegee Syphilis Experiment (1932-1972)
Willowbrook hepatitis vaccination experiments (1956-72)
CIA funded LSD Experiments in Montreal (1950s & 1960s)
Brooklyn Jewish Chronic Disease Hospital cancer study
(1963)
Note: all involved vulnerable participants
The Helsinki Declarations
 1964 – World Medical Associations Declaration of
Helsinki ‘replaces’ the Nuremberg Code
 Since revised in 1975, 1983, 1989, 1996 and 2000
– 2000 version is contained in handout
 Less stringent on consent, allows for proxy consent
 Most other national and international codes now
share this approach
Some Major Ethical/Legal Issues
in Medical Research
1.
2.
3.
4.
Scope of acceptable research
Conflicts of interest
Consent - informed, voluntary
Confidentiality, access to
information
5. Children, mentally incompetent
individuals
6. Justice in recruitment of subjects
Scope of Acceptable Research
 Two issues:
1. Is there some research which should
never be done even if the other concerns
on our list can be met



Xenotransplantation?
Embryonic stem cell research?
Cloning?
Scope of Acceptable Research
 2. What do we do with the results of immoral
research?
– “good science is incompatible with bad ethics”?
– “the Tuskegee study was and remains a key
source of information about … syphilis.” (Caplan,
419)
– “The immorality of research methods should not
blind us to the importance of noting and
discussing them.” (Caplan, 423)
Confidentiality
 General obligation of confidentiality owed by
physicians to patients extends to researchers
 Embodied in research codes, guidelines
 Research Ethics Board’s (REB’s) typically
require policies re. storage and destruction of
data and samples, anonymization of data
 Should also be addressed in consent forms
Confidentiality
 Tension between need to share data and
privacy of subjects
 Beware of over-promising confidentiality:
– Access to data for safety and ethics monitoring
 Health Protection Branch, Health Canada
 Periodic review by REB’s
– General legal/ethical obligations to break
confidentiality
 E.g., child abuse revealed during interview
 Will be discussed in more detail in subsequent session
Confidentiality in Genetic Research
 Genetics raises problems in that the
information gathered through genetic
research is not only information about
an individual, but also about those to
whom the individual is related
– Is there a duty to warn family members of
being at risk?
Research Involving Children
 Application of ‘mature minor’ principle to
research?
 Substitute consent by parents?
– Parents may consent to child’s participation in
research that offers reasonable hope of benefiting
child
 What about research that has no intended
benefit for the child?
– Unclear
Research Involving Mentally
Incompetent Individuals
 Significance - research into Alzheimer’s,
stroke, emergency department research, etc.
 Substitute consent?
 Advance directives?
– e.g. NF Advance Health Care Directives Act
The TCPS (2.5-2.7)
 Research on incompetent subjects may be
acceptable provided that:
– Consent is sought from the appropriate 3rd party
– The subject’s wishes are sought and the subject
does not dissent from the research
– Using incompetent subjects is necessary in order
for the research question to be addressed
– The subjects are not exposed to more than
minimal risks without the potential for benefits to
the subject
Justice in the Recruitment of
Research Subjects
 So why do research on children & incompetent
subjects?
 Clinical research has potential to offer significant
individual benefit
– treatment only available through trial, most up-todate, financial coverage for new medications, etc.
 Also potential future benefit for class of patients
 Historically medications/interventions predominantly
tested on narrow segment of population - youngmiddle aged white males (“the 70 kg man”)
Justice in Recruitment of
Research Subjects
 Optimally, clinical trial sample population should
mirror patient population in clinical practice
 Inclusion of women, the elderly, individuals of
Aboriginal, Asian or African heritage, etc
 Tri-Council Statement 1998
– Anti-discrimination provision, importance of research on
children and elderly