Research Ethics

Philosophy 2803

Lecture VI

Feb. 19, 2003

Research Ethics

§ Medical research shares some issues with medical practice, but also raises some distinct issues

§ Our focus will be on issues surrounding research on human subjects

– Brief history of research ethics

– Discussion of present day standards

– Some Issues in Research Ethics

Some History

§ 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,

– “the founder of experimental medicine”?

– Remember discussion of models for relationships with patients. Paternalism is historically important

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 earlly 20^th century Germany

§ 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 involve 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

– Tuskegee Syphilis Experiment (1932-1972)

– CIA funded LSD Experiments in Montreal (1950s & 1960s)

The Helsinki Declarations

§ 1964 – World Medical Associations Declaration of Helsinki ‘replaces’ the Nuremburg Code

§ Less stringent on consent, allows for proxy consent

§ Since revised in 1975, 1983, 1989, 1996 and 2000

– See pp. 261-264 for 1996 version

Halushka v. U. of Saskatchewan
(1965 – Sask. Court of Appeal)

§ Student paid $50 to participate in anesthetic drug trial

§ Told a catheter (i.e., tube) would be inserted into his left arm

§ Not told the catheter would be advanced into his heart

§ Suffered cardiac arrest, residual injuries

§ Court: duty owed by researchers is “at least as great as, if not greater than, the duty owed by the ordinary physician or surgeon” (p. 260)

§ U. of Saskatchewan held liable

§ Few Canadian cases on research ethics, this case established Canadian standard

Present Day

§ Many codes and policies (e.g., CMA), but no comprehensive legislation

§ Tri-Council Policy Statement on the Ethical Conduct of Research Involving Human Subjects (1998) is most important policy

– Canadian Institutes of Health Research (CIHR)

– Natural Sciences & Engineering Research Council (NSERC)

– Social Sciences & Humanities Research Council (SSHRC)

– Reading on pp. 244-251 is a draft version of this policy

Tri-Council Policy Statement

§ Sets out requirements for research ethics review

– Research Ethics Board (REB)

§ Sets standards on:

– Informed Consent (or Proxy Consent)

– Privacy & Confidentiality

– Conflict of Interest

– Inclusiveness

– Human Genetic Research

– New Reproductive Technologies

Local REBs

§ MUN: Human Investigations Committee (HIC)

– Health related research

§ MUN: Interdisciplinary Committee on Ethics in Human Research (ICEHR)

– All other human subjects research

§ Soon (?) – The Provincial Health Research Ethics Board

– Would be a first in Canada

– Prompted by some research horror stories in NL

Case 1: Dr. A

§ Dr. A. is approached by a drug company about participating in a clinical trial of a new anti-psychotic drug.

§ If he accepts, he will, as usual, hospitalize any ‘new’ psychotic patients he encounters

§ Then, patients will be randomly assigned treatment with either the new drug or a placebo (i.e., a sugar pill)

§ Informed consent will be obtained for each patient (by proxy, if necessary)

– Adapted from Weijer et al, 1997 “Bioethics for Clinicians: 10. Research Ethics.” CMAJ, pp. 1153-4

Case 2: Dr. B

§ Dr. B is a family practitioner whose practice specializes in patients infected with HIV

§ Parasol, a pharmaceutical company, writes to Dr. B requesting that he provide them with the names of patients that might be eligible for enrollment into clinical trials of their new HIV drug.

§ Parasol will pay Dr. B $100 for each name he provides.

– Adapted from Weijer et al, 1997 “Bioethics for Clinicians: 10. Research Ethics.” CMAJ, pp. 1153

Case 3: Dr. C

§ Dr. C approaches the management of a senior’s home about possibly enrolling some of the home’s residents in a clinical drug trial.

§ It is hoped the drug will reduce the progression of Alzheimer’s disease.

§ Dr. C wishes to enroll patients in the middle stages of Alzheimer’s, i.e., suffering some impairment, but not a complete lack of mental capacity

§ The management of the home refuse to even consider the possibility, claiming this research will inevitably “exploit the residents.”

Issues Raised by the Cases: Consent

§ Consent becomes even more important in research ethics than in clinical practice

§ This is because, unlike treatment, research often cannot be justified on grounds of beneficence towards the patient

– Distinction between ‘therapeutic research’ and ‘non-therapeutic research’ important

– Creates problems when dealing with incompetent patients

Issues Raised by the Cases: Consent

§ Dr. A - Consent is not enough

– Harm to patients by being on placebo if effective treatment is already available

– Importance of non-maleficence, particularly in the absence of full autonomy

– A recent development in research ethics

§ At one time, placebo trials were often required

Issues: Conflict of Interest

§ Currently a hot issue, e.g.,

– Dr. B

– Physicians sent to conferences in Aruba by drug companies

– Per patient fees for enrolling patients in clinical trials

§ Are these things acceptable?

– What if Dr. B told his patients about the fee?

Issues: Conflict of Interest

§ Remember: many kinds of conflict of interest

– Fame

– Publishable results

– Tenure

– Medical breakthroughs to benefit society,

– Commercial breakthroughs

§ At a minimum, disclosure of a conflict is morally required

Issues: Confidentiality

§ Confidentiality

– Dr. B - Referral without consent

– Autonomy & Non-maleficence both support confidentiality

§ Under what conditions may information about patients/research subjects be released?

– In clinical practice, very limited exceptions

– Concern with public safety may override confidentiality (E.g., communicable disease, threat to others)

Issues: Confidentiality in Research

§ Clash between confidentiality & need to share data

– Requires efforts to protect & at least disclosure of level of confidentiality

§ Problem of anonymizing data

– Removing name is not always enough

– E.g., study on a outport community that describes a male subject with 3 children & a rare heart condition

§ Genetic research raises some particular problems

– Information is about families, not individuals

– Duty/right to inform relatives of risks we discover?

Issues: Research involving Incompetent Subjects

§ Dr. A, Dr. C: Is it permissible to conduct experiments on incompetent people even with proxy consent?

§ Distinction between therapeutic & non-therapeutic research

– Therapeutic aims at benefiting the patient/subject

– Non-therapeutic may aim at benefiting people with same condition as the subject, but not this subject

– Can appeal to beneficence to justify therapeutic research

– With non-therapeutic research, no autonomy and no beneficence

Issues: Research involving Incompetent Subjects

§ Must not forget need to develop treatments for incompetent patients (Dr. A, Dr. C)

§ General approach is that minimal risk is OK if:

– Substitute decision maker gives OK

– Research cannot be done on competent patients

– Subject does not dissent (ideally, gives assent)

– Research is related to childhood conditions/ appropriate mental condition (see pp. 268-270)

§ Beneficence to group