research involving human subjects: ethics, law and regulation december 2002

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Research Involving Human Subjects: Ethics, Law and Regulation December 2002

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Research Involving Human Subjects:

Ethics, Law and Regulation

December 2002

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?