ETHICAL ISSUES RELATED TO THE PRACTICE OF MEDICINE
Research Ethics
Understanding the history of medical research helps physicians
appreciate the potential for unintended harm and the need for stringent regulations.
[138]
The 1947 Nuremberg Code was developed in
response
to Nazi experimentation on unwilling subjects during World War II.[139]
Designed for legal use, the Nuremberg Code focused on the voluntary consent of the
research subject, the right of the subject to withdraw from the research, and the
need to conform to proper medical standards. It was not widely embraced in its time,
in part because it was often viewed as "a good code for barbarians but an unnecessary
code for ordinary physicians."[140]
The 1964 Declaration of Helsinki promulgated guidelines for physicians.
[141]
The Declaration emphasized that the ethical
principles of research must be adhered to when solely performing research and when
performing research within therapeutic care. Revisions of the Declaration of Helsinki
recommended the concept of the institutional review board and underscored the priority
of the "health or life of the research subject" above the importance of research.
Research abuses have occurred in the United States. In the notorious
Tuskegee Study of Untreated Syphilis, a 40-year study designed to observe the effects
of syphilis on African-American men, investigators lied to subjects and did not offer
antibiotics when their efficacy was recognized approximately 15 years into the study.
At the Willowbrook State Hospital from 1956 to 1972, researchers infected mentally
retarded children with hepatitis in the hope of developing a vaccine. In the 1960s,
live cancer cells were injected into indigent, elderly patients without their consent.
The researcher had permission of the hospital's medical director despite the objections
of colleagues. In the 30 years after World War II, the United States government
conducted dangerous radiation research on individuals without their consent.[142]
These events suggest that there was little thought or knowledge about the role of
research and protection of research subjects.
Dangerous practices in medical research were brought to the forefront
in 1966 by the anesthesiologist and medical ethicist Dr. Henry K. Beecher in his
seminal paper, "Ethics and Clinical Research."[143]
Beecher detailed 22 examples of unethical or questionably ethical research projects
published in the peer-reviewed scientific literature. His article is credited with
stimulating the government action on oversight of federally funded research that
eventually gave rise to institutional review boards.
In the United States, the National Institute of Health's Policies
for the Protection of Human Subjects were first issued in 1966 and were raised to
regulatory status in 1974. In 1974, the National Research Act established the National
Commission for the Protection of Human Subjects of Biomedical and Behavioral Research,
in part to identify the ethical principles that should underlie the conduct of research
involving human subjects and to develop guidelines that should be followed to ensure
that such research is conducted in accordance with those principles. This group
published the Belmont Report in 1979, which emphasized the need for ethical research
to adhere to principles of respect for persons, beneficence, and justice. Respect
for persons recognizes the personal dignity and autonomy of individuals
and the need to protect those with diminished autonomy. Beneficence
obligates investigators to protect persons from harm by maximizing anticipated benefits
and minimizing risks of harm. Justice requires the
benefits and burdens of research to be distributed fairly.[144]
The primary office responsible for human subject protection is
the Office for Human Research Protection of the U.S. Department of Health and Human
Services. The primary regulation, Code of Federal Regulations Title 45, Part 46
Protection of Human Subjects, applies to all research involving human participants
that is conducted or supported, in whole or in part, in foreign or domestic settings
by the Department of Health and Human Services.[145]
The colloquial term common rule is used for all
federal regulations that cover the protection of research subjects. The common rule
is continuously revised.
The common rule suggests characteristics of proper research ( Table
89-6
). A poorly done study wastes resources and puts subjects at risk,
and if published, it may affect treatment decisions and harm patients. Institutional
review boards help ensure the previous principles are met by monitoring and safeguarding
the quality of the research and through the informed consent processes. An example
of why clarity in informed consent for research is important is what is known as
therapeutic misconception. Patients have difficulty
understanding that experiments are not designed to improve their own care.[146]
Over the past few years, several issues have emerged. Determining
which activities are quality improvement and which are research is difficult. The
definition of research—"a systematic investigation, including research development,
testing and evaluation, designed to develop or contribute to generalizable knowledge"
[147]
—suggests that a primary distinction
is
whether the intent of the activity is to contribute to generalizable knowledge or
whether the intent is to improve an institutional specific activity.
Another difficulty being addressed is research in emergency situations
in which it is impossible to obtain informed consent. The requirements to achieve
a waiver for informed consent in these situations are that subjects are in life-threatening
situations, available treatments are unproven or unsatisfactory, and the collection
of valid scientific evidence, which may include evidence obtained through randomized,
placebo-controlled investigations, is necessary to determine the safety and effectiveness
of particular interventions.[148]
Other conditions
to achieve
TABLE 89-6 -- Patient and societal attributes of ethically sound research
|
Informed consent |
|
Statement of purposes of research |
|
Expected duration of the subject's participation |
|
Description of procedures to be followed |
|
Identification of experimental procedures |
|
Foreseeable risks or discomforts to the subject |
|
Benefits to subject or others that may be reasonably
expected |
|
Alternate procedures or courses of treatments and
their risks and benefits |
|
Extent of confidentiality |
|
Nature and extent of known risk |
|
Possibility of unknown risk |
|
Compensation and treatments for side effects |
|
The right to withdraw without penalty |
|
Quality care for the subject and legitimate options for the nonparticipant |
|
Proper subject selection requirements |
|
Scientific validity to ensure the study can sufficiently benefit
the subject or science as a whole with respect to the incurred risk |
|
Accurate and prompt publication |
|
Independent review by institutional review boards |
|
Data from references [145]
[207]
[208]
and
[209]
. |
a waiver for informed consent include the premise that obtaining informed consent
is not feasible and that participation in the research holds out the prospect of
direct benefit but the clinical investigation could not practicably be carried out
without the waiver.
