Transcript research_ethics_2011 - ethicsandcriticalreasoning

Ethics and medical research
Dr Anna Smajdor
Lecturer in ethics
University of East Anglia
[email protected]
Ethics is about right and wrong:
what ought one to do? – Socrates
Ethical questions can’t be answered simply
by referring to a) external facts, b) the law,
c) religion, d) public opinion.
Q: Is it acceptable to perform research on
participants without their consent?
Ethical arguments
Claim: ‘performing research without participants’ consent is wrong’
Arguments (an argument is a conclusion supported by one or more
reasons):
1. It is wrong to harm people
2. performing research without consent harms people
Conclusion: it is wrong to perform research without consent
DISAGREE? Show where the argument is flawed….
Potential challenges:
‘Harming people is not always wrong’ – rejects 1st claim
‘Research without consent does not necessarily harm people’ – rejects 2nd
claim
‘Research without consent is not wrong because it harms people, but for
other unrelated reasons’ – accepts that the argument is flawed, but
suggests the conclusion is justified on separate grounds: need to
draw up new argument
Argument and theory
All ethical theories are based on underlying argument.
Utilitarianism:
1. It is good to benefit people
2. It is bad to harm people
Therefore: any research practice is ethically acceptable if it
promotes more benefit than harm
Deontology:
1. We should always follow moral rules
2. It is a moral rule never to treat someone as a mere means
Therefore: any research that involves treating someone as a
mere means is unethical
First steps towards ethical governance
 1898 Albert Neisser: injected serum from patients with
syphilis into patients who were admitted for other medical
conditions.
 Patients not informed about the experiment nor asked for
their consent. Some of them contracted syphilis.
 Neisser argued that the women contracted the disease
because they worked as prostitutes, not as a result of the
‘vaccine’.
 Newspapers published these and other cases, triggering
public debate.
 The scientific community, almost without exception,
supported Neisser.
 Public opinion differed & guidelines were issued insisting
on informed consent for research participants.
Nazi research
 High altitude experiments at Dachau – subjects placed in a
low pressure chamber + pressure was gradually reduced.
Many died, others endured agony during the experiments,
and suffered lifelong damage.
 Freezing experiments at Dachau – subjects immersed for
hours in tanks of freezing water. Many died
 Sterilisation experiments at Auschwitz – inmates subjected
to X-rays, surgery and drug interventions, rendering them
sterile
 Poison experiments at Buchenwald – inmates given poison in
their food. Those not killed by the poison were executed +
postmortems carried out
Scientific ideology
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Association between scientists + doctors
Use of science to pursue ideals
Language of hygiene and health
Species/race benefit vs individual benefit
Some arguments put forward by those on trial:
• Carrying out orders - deontology
• Urgency of wartime situation - utilitarianism
• Acting within the law at the time - deontology
• The death of a few prisoners would save many
German lives - utilitarianism
Learning from the past
Why were the Nazi experiments unethical?
Coercion – gun to the head situation
Abuse of power
Abuse of privilege, eg high status of doctors
Vulnerable subjects
Excessive risks/harms to subjects
Results of research only designed to benefit a limited group (eg
German citizens) at the expense of others
• ?Validity of scientific data?
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Nuremberg trials 1945-1949
• Exposed dangers of eugenic/racist ideologies
• Revealed doctors’ exploitation of prisoners
• Brought Nazi experiments to public view
• Highlighted lack of ethical code for research
• Resulted in the Nuremberg Code
• Followed by the Declaration of Helsinki 1964
• Formation of ethics committees
Ethical dilemma: use of Nazi data
 Question of scientific validity
• Is unethical science always bad science?
• EG immersion experiments on already weak/emaciated
subjects
• But still viewed as having scientific value
 Who would it harm?
 Could it benefit anyone?
 Is there a greater value at stake?
• EG social expression of revulsion at Nazi crimes
 Can’t prevent harm after it's happened
 Does it set a precedent?
• If data obtained unethically can be published & cited,
unethical scientists may still benefit – no incentive to
conduct research ethically
Ethical principles and medical research
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Autonomy of research participants
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Avoidance of harm to participants
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Consent
Absence of coercion
Full information
No inducement (eg large financial incentives)
Use competent participants wherever possible
Risks should be minimal
Researchers should use least harmful means possible
Participants should be made aware of potential harm
Scientific validity
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Is the study necessary
Is its methodology likely to yield useful/valid results?
Are its results likely to be beneficial/therapeutic?
Another notorious example
Tuskegee Syphilis study 1932-1972
– Long-term progression of syphilis in black men studied
– Participants: African-American men, mostly with very
limited educational attainment
– Treatments at the time highly toxic –non-intervention
might be best approach
– Consent not obtained from participants – the research was
mostly observational
– Participants rewarded with free medical treatment for other
conditions, meals, transport to clinics
– Effective treatment became available during the study, but
would interfere with scientific purpose, eg to discover
progress of disease in black men, therefore not offered to
participants
Would you give ethical approval for this study?
a) to commence in 1932
b) to continue after effective treatment discovered?
Purpose/benefit of study
 Study designed to benefit the population. Participants might benefit if
non-intervention proved best approach, but this remained to be
established. Participants benefited from extra access to medical services
+ meals, etc.
 No scientific justification for study after treatment became available?
Autonomy
 No consent; primarily observational study
 Respect for autonomy => full information?
 Possibility of inducement free medical treatment + meals, etc
Harm (question of active vs passive?)
 Mostly observational, little actual intervention
 Many died as a result of their disease
 Many participants’ wives and children were affected with the disease
Justice
 Would white participants have been treated in the same way...?
Autonomy, paternalism & research
Does consent make ANYTHING morally permissible?
Hypothetical scenario: Mr X freely consents to allow his head to be
surgically removed and re-attached for the purpose of research. Is
this ethically acceptable?
Two options:
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Paternalism – prevent people from doing risky things/making bad
choices
Libertarian – people have the right to choose what they want, whether
or not it is deemed harmful by others.
What if someone is not competent? EG children; unconscious adults, or
mentally ill?
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Inclusion in research only if no option for using competent adults
If the risks of harm are carefully ascertained
Assent should be obtained where possible
Willowbrook study
Willowbrook: a school in New York City for children with learning
disabilities. From 1963-1966 research carried out on
Willowbrook Children:
 Children deliberately infected with hepatitis
 Treated with experimental cures
 Effectiveness of cures monitored
As with Tuskegee, note vulnerability of participants:
subjects already marginalised members of society
Question: at Tuskegee and Willowbrook, were vulnerable
participants chosen
a) because they were easier to access?
b) or because there was a scientific justification?
Subsequent reports revealed severe overcrowding & unhygienic
conditions. Willowbrook School eventually closed
When research goes wrong
Northwick Park 2006: 8 healthy volunteers
recruited for a phase 1 clinical trial. 6
injected with active agent (a T-cell agonist);
2 receive placebo.
The 6 volunteers suffered catastrophic multisystem failure.
Life threatening responses – lengthy ICU treatment, loss of
extremities, ongoing health problems + elevated cancer risk.
Does this mean the research was unethical…?
Impossibility of removing all elements of risk from medical
research – this is the whole purpose of human trials.
BUT – were there ethical problems with the trial anyway?
Ethical concerns re Northwick Park
Autonomy - were the participants:
a) coerced?
b) enticed?
c) misinformed?
Risk/benefit: were the harms excessive?
EG grounds for paternalist intervention?
Had researchers been negligent in assessing risk?
Animal trials didn’t reveal such high risks
But how applicable are animal tests to humans?
“Relative lack of severe toxicity in animal models should never be
construed as a guarantee of safety in man, as the story of
thalidomide taught us.”(Goodyear, BMJ)
Why did the injections continue after adverse
effects became evident?
Summary of national & international guidelines
1. Risk to participants kept as low as possible
2. Participants should be fully informed
3. Research without consent, eg patient notes, OK only if:
 it is important enough to justify non—consent and
 there is no other way of reaching the end goal
4. Coercion must be avoided at all costs
5. Expense payments must be reasonable + not constitute
an inducement
6. Research on non-competent subject justified only if:
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risk of harm minimal
research aims cannot be achieved by other means
the research is of significant value
a relevant person gives valid consent
(Hope et al)
References and further reading
[Image on slide 1: A cartoon by James Gillray, published in 1801,
depicting Edward Jenner at the Smallpox Inoculation Hospital, St
Pancras, London, vaccinating the populace with cowpox.]
Vollman J, Winau R. Informed consent in human experimentation
before the Nuremberg Code. BMJ 1996;313:1445-50.
Pellegrino E. The Nazi Doctors and Nuremberg: Some Moral Lessons
Revisited. Annals of internal medicine. 1997. 127:4; 307.
Hope T, Savulescu J et al. Medical ethics and law. 2nd Edition. 2008.
Elsevier.
Beauchamp T L, Childress J F. Principles of Biomedical Ethics. Oxford
University Press. 2001.
Krugman S. The Willowbrook hepatitis studies revisited: ethical
aspects. Rev Infect Dis. 1986 Jan-Feb;8(1):157-62.
Goodyear M. Learning from the TGN1412 trial. BMJ. 2006;332:677678.
http://www.nres.npsa.nhs.uk/