research involving human subjects: ethics, law and regulation december 2002
TRANSCRIPT
William Beaumont & Alexis St. Martin
Beaumont carried out a series of experiments on Alexis St. Martin over a period of many years
Was Beaumont a pioneer in ethical research or someone who abused his research subject?
– Be careful of applying present-day standards to historical figures
– The prime value of this case lies in what it tells us about how to do things today, not whether Beaumont was a good or bad man
Beaumont (1785-1853)
Had a 2 year apprenticeship with a country doctor
Enlisted as a surgeon’s mate in 1812. Briefly left the army after the War of 1812, but rejoined as a surgeon in 1820
1822 – Encounters St. Martin
1833 – Experiments and Observations on the Gastric Juices and the Physiology of Digestion
– “produced a picture of the living stomach that has required only a little updating in the century and a half since he made his observations.”
St. Martin (1803?-1880)
June 6, 1822 – St. Martin, a French-Canadian working for the American Fur Company, was accidentally shot in Northern Michigan
The result was a fistula exposing part of St. Martin’s lung and stomach
St. Martin survived, but the fistula never closed fully
After 8-10 months of attempts to close it, Beaumont concluded that the only means of doing so was to suture the sides together, “an operation to which the patient would not submit.”
The Experiments
First experiment in May, 1823?
– Administering a cathartic by pouring it in
Literally hundreds between 1825 and 1833, most involving inserting or removing material through the ‘valve’ in St. Martin’s stomach
The Relationship
1825 – Beaumont carried out experiments from May-August then St. Martin “returned to Canada … without obtaining my consent.” (18)
– In correspondence, Beaumont described this as a “faithless absconding”.
1829 – St. Martin enters Beaumont’s “service” in August
– St. Martin “performed all the duties of a common servant” when experiments were not being carried out. (19)
– This continues until March, 1831, when Beaumont allows St. Martin to return home.
The Relationship
1832 – In October, St. Martin returns.
– The two sign a contract binding St. Martin to “obey,
suffer & comply with all reasonable & proper orders or experiments.”
– In exchange, St. Martin was to receive $150 plus room and board.
– In 1832, St. Martin was persuaded to join the U.S. Army for a period of 5 years. He was eventually assigned to Beaumont as an assistant
The Relationship
1833 – A new contract is signed, for 2 years at $200 a year
Shortly afterward, Beaumont advances St. Martin some of the $200 in order for St. Martin to return his family to Canada.
St. Martin never returned, although Beaumont made increasingly lucrative offers ($500/year in 1850, shortly before Beaumont’s death)
Beaumont as Medical Ethics Pioneer?
Beecher (1970) credits Beaumont with producing the “oldest American code” concerning human experimentation:
– “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.”
There is, however, some dispute about whether this code actually existed. (Numbers, 1979)
Some Issues
When did Beaumont take St. Martin into his home?
– Beaumont tells us it was before he began using St. Martin as a research subject. Others (Numbers, 1979) say it was after.
Returning to Canada “without my permission”?
Some experiments clearly caused St. Martin discomfort
Payment for participation in research
Outline
A. what is research?
B. rationale for research ethics review
C. ethical/legal/regulatory framework for human subject research in Canada
D. some major ethical/legal issues in biomedical research
What is Research?
sometimes difficult to distinguish research from therapy:– often carried out simultaneously– investigators often physicians– terminology - “therapeutic research”, “clinical
research”, “experimental interventions”– research vs. “innovative care”
Research and/or Therapy?
Why is the distinction important?– determines whether particular set of regulations
or research ethics guidelines must be followed– determines whether prior approval by a Research
Ethics Board (REB) is required– affects the legal standard for disclosure of
information– may affect ability of substitute decision-maker to
give consent
What is Human Subject Research?
“the generation of data about persons, through intervention or otherwise, that goes beyond that necessary for the person’s immediate well-being”
1987 MRC Guidelines
an activity that involves “a systematic investigation to establish facts, principles or generalizable knowledge”
1998 Tri-Council Policy Statement: Ethical Conduct of Research Involving Humans
Rationale For Research Ethics Review
part of crucial system of checks and balances safeguard rights and well-being of research
subjects address actual, perceived, potential conflicts
of interest reinforce and rehabilitate public trust in
medical research
Rationale For Research Ethics Review
inherent tension between primary aims of research and treatment
when patients participate in clinical research, physician-investigator may experience this tension
notion of “clinical equipoise”:- RCT’s ethically acceptable where expert community in state of
honest professional disagreement as to relative merits of two
alternatives
Research Codes and Guidelines
primary purpose - to protect the physical well-being, dignity and integrity of individuals who serve as participants
interests of investigators in pursuing their professions
interests of society in increasing knowledge re public and individual health
Historical Context
will be covered in future session several instances of research controversies
and atrocities in many different countries a number of international instruments have
been developed to try to address ethical standards and regulation of human subject research
Governance of Human Subject Research in Canada
in Canada, no comprehensive legislation to regulate all research involving humans
- biomedical research governed by law that is primarily directed to other purposes
- some legislation applies almost inadvertently to research
- other legislation re health care deliberately excludes research from its ambit
- role of the common law- consent, negligence, etc.
- Quebec - Civil Code
Newfoundland Legislation
some statutes in NF containing provisions applicable to research:
- Advance Health Care Directives Act
- Access to Information and Protection of Privacy Act
- Hospitals Act
- Human Tissue Act
Codes, Guidelines and Policies
these “extra-legal instruments” play important role in regulation of research in Canada
promulgated by governmental bodies, funding agencies, professional organizations and local institutions
ethics codes, guidelines and policy statements usually lack means of direct legal enforcement
however may be relied on by courts to indicate applicable standards of conduct
Tri-Council Policy Statement on the Ethical Conduct of Research Involving Human
Subjects (1998) MRC, NSERC, SSHRC context - the need for research, guiding ethical principles,
“subject-centered perspective” research requiring ethics review, REB’s consent, confidentiality, conflict of interest inclusion in research - women, incompetent individuals,
aboriginal people clinical trials human genetic research, research on embryos/fetuses and
human tissues
CMA Code of Ethics
duty of physicians to obtain from research ethics committee review and approval of research involving humans
duty of physicians to obtain informed consent from potential research subjects
duty to report unethical research behaviour
Some Major Ethical/Legal Issues in Medical Research
1. conflicts of interest
2. consent - informed, voluntary
3. confidentiality, access to information
4. scope of acceptable research
5. children, mentally incompetent individuals
6. justice in recruitment of subjects
Conflicts of Interest
investigator’s interests - fame, publishable results, medical breakthroughs to benefit
society
financial conflicts of interest- pharmaceutical companies
- partnerships between academic institutions and corporations
- commercial value of research results
Conflicts of Interest and REB’s
one role of REB’s is conflict of interest oversight:
- financial conflicts
- impact of conflicts on informed consent
conflicts of interest involving the REB:- membership, operation within institution
- collegiality, concerns about promotion, bringing valuable research funding into institution, etc.
Consent - General Principles
capacity- must be given by person legally capable of making decision
voluntary- no coercion/undue influence
specific- to procedure(s), physician(s) involved
informed- disclosure/discussion required
Consent to Research in the Courts
two categories of research dealt with differently by the courts:
1. consent to research with no intended benefit for participants
2. consent to research with intended benefit with participants
Research with no Intended Benefit for Participants
Halushka v. U. of Saskatchewan (Sask. C.A. 1965)- healthy university student paid $50 to participate in
anesthetic drug trial, requiring cardiac catheterization
- told test was “nothing to worry about”
- suffered cardiac arrest, residual injuries
Court held: duty of disclosure of investigators at least as great as, if not greater than, duty of ordinary physician/surgeon to patient
- full and frank disclosure
- no “therapeutic privilege”, no waiver
Research with no Intended Benefit for Participants
Weiss v. Solomon (Que. Sup. Ct. 1989)- trial of ophthalmic drops in reducing post-op retinal edema
- fluorescein angiography used to verify effects of drops
- told risks: discomfort, nausea and minor allergic reactions
- patient died from severe allergic reaction
Court held: investigator and REB at fault for failure to warn of all the risks involved in the research
- all risks must be disclosed, even if rare/remote, particularly if serious consequences
- court based decision in part on Helsinki Declaration
Research with Intended Benefit for Participants
no Canadian cases involving research pursuant to protocol reviewed for ethical/scientific merit
cases involving individual MDs testing therapeutic innovations of their own design in course of Dr.-pt. relationship
courts have applied standard of disclosure generally applied to Dr.-pt. relationship - “What would reasonable pt. want to know?
fact that procedure “unique” or “experimental” something most people would want to know
Confidentiality
general obligation of confidentiality owed by physicians to patients extends to researchers
embodied in research codes, guidelines 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
- genetic research- right to know/right not to know?
- duty/right to inform relatives of their risks?