Download Research Ethics and - Escuela de Medicina UC

RESEARCH ETHICS:
SOME BACKGROUND
Richard Carpentier, Santiago, November 3,
2011
Introduction
• I would like to ground my intervention on the one hand in a
conception that makes essential distinctions between ethics
and morality and on the other in medicine as a moral
profession insofar as there is a large moral consensus on
medicine as seeking essentially to benefit the patient.
• Historically, there is evidence that ethics and medicine evolved
in parallel in Greek culture and that they nurtured each other.
• Ethics learned from medicine the uniqueness of persons and
situations as well as appropriate perception being the condition
of an appropriate response. It also learned that the real person
is the basis for moral judgments.
• Medicine learned about appropriate goals for life, service to the
state and a good life being paramount.
ETHICS AND MORALITY
The Ethical Intention
• Ricœur defines the
“ethical intention” as
aiming at the “good
life” with and for others,
in just institutions.
• Oneself as Another, 1992, 172.
Paul Ricœur, 1913-2005
Ethics and Morality
I propose to reserve the term
“moral” as the fix reference term
and to assign to it a double
function, that to point to the region
of the norms, said otherwise what
is allowed or forbidden, on the one
hand, and on the other the sense
of obligation as the subjective
face of a relationship of a
subject to the norms. As far as I
am concerned, this is the fixed
point, the hard nucleus.
De la morale à l’éthique et aux éthiques, undated
conference, Montréal
Paul Ricœur, 1913-2005
Ethics and morality
• Ricœur roots the norms in real life and desire, as did
Aristotle but he is also careful to insert them in concrete
situations.
• This way, morality is preceded and followed by ethics,
both as a guide and a reality check.
• So, as we move forward with our discussions, we are
reminded of the importance of these distinctions and of
the fact that ethics and morality are different but both
important and complementary.
Ethics and morality
• But if morality is to be the real thing as Ricœur says, we
need to look back at how we think about it.
• Time is short here, but I want to introduce an important
idea which should get us thinking.
• The last decades have seen a return of ethics in the
forefront. Especially an ethics characterized by a
imperialism of principles and an abandonment of the real
person in concrete situations.
• A rationalistic ethics, oblivious of morality and of what are
the real springs of action, be it our upbringing in a family
and society, our nervous system and the inner
organization of our brain with its ancient structures
explaining emotions, desires, fear, etc.
Morality is from Unconscious Origin
• The head is ever the dupe of the
heart. (102)
• A man often believes himself
leader when he is led; as his
mind endeavours to reach one
goal, his heart insensibly drags
him towards another. (43)
• Maximes
François de La Rochefoucauld
(1613 –1680)
Disappearance of the Real Person
In the 1780’s, the moral agent
as traditionally understood
almost, if not quite,
disappeared from view. The
moral agent’s character, the
structure of his desires and
dispositions, became at best a
peripheral rather than a central
topic for moral philosophy.
Alasdair MacIntyre, How Moral Agents
Became Ghosts, Synthese, 1982, 53, 295
Alasdair MacIntyre, 1919-
The Art of the Right Perception
• Wherefore the greater complexity these ills
requires a more exact method of treatment. For it
is necessary to aim at some measure. But no
measure, neither number nor weight, by reference
to which knowledge can be made exact, can be
found except bodily feeling (aisthêsis).
• Ancient Medicine, chapter 9
Hippocrates, Ancient Medicine, Trans. WHS Jones, Chapter 9.
CLINICAL RESEARCH AND
VULNERABILITY
Back to patients
• As we move to the topics of tomorrow presentations, we
are reminded of the specificities of the patient population,
being cancer patients. There are general characteristics of
patients in general and of their attitude towards
participation in clinical research, captured in the following
survey results which apply especially well to cancer
patients.
• Harris Interactive, New Survey Shows Public Perception
of Opportunity to Participate in Clinical Trials Has
Decreased Slightly From Last Year, Healthcare News
5(6) June 27, 2005.
% 2004
% 2005
If I had a terminal illness
72
72
If I thought the drug might cure me
71
67
If there were no other medical options available to me
67
66
If I knew there were no risks involved
67
61
If I thought the drug/treatment would help me
57
61
If the treatment were free of charge to me
64
53
If my doctor recommended it
54
47
If I received money for participating
56
46
If I knew the risks associated with the treatment
49
45
If I thought the drug/treatment would help someone else in future
NA
45
If it were convenient for me to participate
53
43
If the location were convenient for me
54
43
If there were minimal side effects associated with the treatment
48
43
If I knew I would receive an active treatment, not a placebo
37
33
If I knew someone else who had the condition being studied
NA
30
If I had a condition other than a terminal illness
38
29
If I take a drug/treatment made by same pharmaceutical company
NA
28
Would consider participating in clinical research study
Why do patients participate?
• Not wanting to give up, to help other cancer patients, for
their family and to have someone to talk to
• Patients in early anticancer trials will take part because of
the intense support offered
Cox and McGarry. Eur J Cancer Care 12: 114, 2000
Why do patients participate?
• “therapeutic misconception”
• “many participants believe that clinical trials
provide individualized treatment and direct
benefit to subjects”
• 43% of oncologists enrolled patients…to make
sure they got state-of-the-art treatment
Lo and Guerin, Cancer Clinical Trials: Proactive Strategies, 2007.
Defining vulnerability
• Definitions of vulnerability may be inward looking or they
may be outward looking. These are somewhat arbitrary
categories that I introduce.
• For example, being vulnerable may be equivalent to being
fragile, inward looking, or to being unable to protect
oneself, outward looking. So, not so much a characteristic
of the being as a characteristic of the relationship
between beings.
• You will note that both examples here refer to ‘being’, that
is to something essential to who we are, at least in certain
circumscribed circumstances.
Vulnerability as Incapacity to Protect one’s interests
• Vulnerability can be broadly defined as the
inability to protect one’s interests. In
relation to medical research, vulnerable
individuals or populations are at increased
risk of being harmed by research due to a
decreased capacity to protect their
personal interests.
Ballantyne, A., Rogers, W., Vulnerability and Protection in Human
Research, Harvard Health Policy Review, 8 (1), 2007, 30.
Outward looking definition
• These definitions are reminding us of an
important value in our western culture, that of
autonomy, literally the capacity to decide for
ourselves, to lay out our own norms.
• This has been an important feature of the ethics
of research over the last 30 years or so,
reinforced by the Belmont Report from the
National Commission for the Protection of Human
Subjects of Biomedical and Behavioral Research
(1974-1978) that came up with a set of guiding
principles: autonomy, beneficence, and justice.
Responsibility is for the fragile, the vulnerable
Any active responsibility starts
with the question: What will
happen to him if I do not take
care of him. The more the
answer is obscure, the more
clearly it is presenting itself.
Fear that is an essential part of
responsibility is not the one that
council us not to act, but rather
the one that invites us to act.
Hans Jonas 1903 - 1993
The Imperative of Responsibility, The University of Chicago Press, 1985.
Responsibility is for the fragile, the vulnerable
• This fear that we are
aiming at is the fear for
the object of
responsibility. It is an
object that is
fundamentally fragile
for which it is possible
to fear something.
Hans Jonas 1903 - 1993
The Imperative of Responsibility, The University of Chicago Press, 1985.
Inward looking definition
• Jonas’ definition gets to the heart of the problem faced
when dealing with recruitment of seriously ill patients, that
is that they are fragile and they may die, they are
essentially vulnerable as they may perish. And that we
have a responsibility, as clinicians-researchers and REC
members, to protect and promote the fragile, the
vulnerable. But the cycle that leads to taking action to
protect stars with the perception of the fragility.
• And both the risks and the absence or low probability of
benefits that are associated with phase 0 and phase 1
cancer trials do exacerbate the vulnerable status of the
patient.
Ethical Issues in Phase 0 Trials
• Early determination whether a new drug is good
candidate for further trials
• Subclinical dosage means no benefit can be gain
• TGN1412 trial in London shows small dosage may have
unexpected catastrophic results
• Patients in desperate situation will do anything to help
themselves and others, compromising the independence
of consent
Ethical issues in phase 1 oncology trials
• Because one of the end points of phase one oncology
trials is toxicity, this is one area where voluntary
volunteers give their place to affected individuals in phase
1 trials.
• There are three primary ethical concerns associated with
phase 1 trials
Ethical issues in phase 1 oncology trials
• 1- The risk to benefit ratio is inherently unfavourable for
research subjects
• 2- They enroll patients whose ability to provide valid
informed consent may be compromised, and
• 3- They may take advantage of vulnerable subjects.
• In some of these studies, any benefit to the subject is, at
best, highly unlikely. Subjects may experience a decline in
health status from their participation, no improvements in
terms of quality of life, or only a short prolongation of life.
Abdoler, E., et al., The Ethics of Phase 0 Oncology Trials,
Clinical Cancer Research, 14 (2008, 3692-3.
ABOUT RESEARCH
ETHICS COMMITTEES
Introduction
• REC have been establish to introduce independent judgment in
the research process after the Second World War and the
atrocities o all parties in research (Germany, Japan, US)
• We expect a lot from REC, they should know everything, they
should be virtuous, ingenious, generous with their time, be
independent, etc.
• But that is not always the case. Hundreds of visits of RECs in
hospitals and universities have shown most of them lack the
competence to do their work appropriately.
• Another issue is that they are not as independent as we think
they are and patients expect they are. Nothing requires them to
be independent of institutions where research is carried out.
Primary interest of IRB
• The primary interest of IRBs is to ensure that the rights
and welfare of research participants are fulfilled. All other
interests are secondary, including personal or institutional
financial gain. When a person's financial concerns have
the potential to conflict with the protection of participants,
a FCOI exists.
Campbell, EG, Concerns about IRBs in the enterprise of clinical research,
The Lancet Oncology, 5 (1) 2004, 326.
Subjects believe there are safeguards
against conflicts of interest
• Of the patients surveyed, 62% believed there was an
oversight system in place to monitor financial ties.
However, when asked, most could not specify a system
but suggested that there “must be a process during study
implementation,” such as an “independent oversight
committee to screen M.D.’s credentials and relationship
with drug companies.” One third of the patients did not
know whether there was such an oversight system.
Hampson, LA et al, Patients’s Views on Financial Conflicts of Interest in Cancer
Research Trials, New England Journal of Medicine, 355;22, 2006, 2334.
A natural tension within the mission
• ‘A natural tension exists as an IRB attempts of fulfill its
mission of providing an independent and unbiased
evaluation of a study while also insuring appropriate
consideration of all relevant risks, benefits, and
alternative strategies. IRB members with often critically
relevant knowledge of unique issues involved in a
protocol under review may be the individuals with the
greatest potential for a perceived “conflict,” due to current
or past involvement in sponsor-associated research in the
particular area.’
• Campbell, Cancer Investigation, 26, 115-117, 2008.
REC members financial COI may
undermine objectivity
• "Financial relationships with study sponsors create
competing interests that could undermine the objectivity of
the IRB process. Policies and practices regarding the
disclosure and management of such relationships among
IRB members need to withstand intense scrutiny, and our
results suggest that we can do much better. »
• EG Campbell, cited in Osterweil, N. Many Clinical Trial Overseers Have
Conflicts of Interest ,MedPage Today, November 29, 2006
Conflicts of interest for Research Ethics
Committees
• … the ethical review of research protocols is
generally performed within and by employees
of the very institutions in which the research
will be carried out, a clear conflict of interest.
• T.L. Beauchamp, The (mis)used of informed consent in medical research,
Journal of Internal Medicine, 269, 2011, p. 383.
When we need to retain the services of the clinicianresearcher
• In the case of smaller or regional hospitals, there might
occur a conflict originating in the will or need to retain the
services of a difficult to recruit specialist.
• Very specialized surgeons for examples or anaesthetists
are difficult to recruit. If the REB turns down a protocol,
they may choose to go elsewhere.
THANK YOU!