The Ethical Structure behind
Human Experimentation
Curtis Jantzi
November 25, 1996
Biology Senior Seminar
Outline
I. Introduction
II. History
III. Formation of Internal Review Boards (IRB)
IV. Conceptual problems encountered by IRBs
V. Track record of IRBs
VI. Conclusion
Introduction
The history of medical research in the twentieth century provides abundant
evidence which shows how easy it is to exploit individuals, especially the
sick, the weak, and the vulnerable, when the only moral guide for science
is a naive utilitarian dedication to the greatest good for the greatest
number. Locally administered internal review boards were thought to be a
solution to the need for ethical safeguards to protect the human guinea
pig. However, with problems surrounding informed consent, the differentiation
between experimentation and treatment, and the new advances within medicine,
internal review boards were found to be inadequate for the job. This led
to the establishment of the National Bioethics Advisory Commission by President
Bill Clinton in the hopes of setting clear ethical standards for human research.
History
Examples of unethical human research cases
The dark history of human experimentation began with the clarification between
experimentation and treatment. The larger public began to notice experimenters
ethical neglect for their subjects in the early 1960s. Those charged with
administering research funding took note of the public furor generated by
the exposure of gross abuses in medical research. These included uncontrolled
promotional distribution of thalidomide throughout the United States, labeled
as an experimental drug; the administration of cancer cells to senile and
debilitated patients at the Brooklyn Jewish Chronic Disease Hospital; and
the uncontrolled distribution of LSD to children at Harvard Medical Center
through Professors Alpert and Leary. Most important was Henry Beechers 1966
article in the New England Journal of Medicine, detailing 22 protocols
of dubious ethicality and declaring that the roster had been winnowed down
from a longer list culled more or less from periodicals crossing his desk
(Edgar, 495).
Publics fears concerning these cases
The public was very sensitive to these experiments since the US government
had imprinted the crimes committed by the Nazi doctors throughout the war
into their minds. When the public became aware that their own government
was capable of the same devious unethical experimentation, two fears arose.
The first was the frightening power of some political ideologies to demand
that no private interest impede the accomplishment of the public good, and
the second was the acute fear that people must adapt to whatever science
produces, and that science is ultimately beyond social control (Edgar 496).
Therefore, the U.S. government changed their slogans to focus on how the
Nuremburg trials taught us that there must be limits to government power.
If Nuremberg was one critical underpinning for public attitudes toward human
experimentation, the second was the social awareness that new medical breakthroughs
affected not simply the individual patient, but also human life more generally.
Given the dimensions of the potential transformation, the innovations had
to be reviewed and authorized by someone other than the particular investigators.
The scientific community was already leaning this way. The most noteworthy
example for this time was the Seattle doctors move to establish a lay kidney
dialysis committee for the purpose of deciding who received the life saving
benefits. The tipping point toward developing organized committees to review
research was crossed when physicists watched the mushroom cloud while realizing
they had altered the course of history without securing a societal consensus
about the wisdom of doing so.
Governments response
Federal regulations grow out of and express the social values and concerns
of its people. With each new example in researchers neglect of human rights
being brought to the attention of the public, the government would have
been deaf not to have heard and reacted to the outcry by its people. The
people were demanding for ethical principles to be joined with political
ideals, aesthetic standards, and other norms to inform administrative decisions
(Williams 169).
The government responded to the publics distress by forming the National
Commission for the Protection of Human Subjects of Biomedical and Behavioral
Research (The National Commission) in 1978. The regulations that followed
from their work were designed to protect experimental subjects autonomy
by requiring voluntary, informed consent, to protect subject and public
welfare, to protect privacy and maintain confidentiality of data, and to
ensure equability in the selection of subjects (Williams 172). They accomplished
this by transferring a great deal of authority from central bureaucracy
that funded research to the newly-created Institutional Review Boards (IRB).
The National Commission set up the following guidelines for the IRBs principles
of decision making: decisions should be made in an informed manner, decisions
should be made with ample time for deliberation and reflection, decisions
should be made under calm circumstances, decision makers should be willing
to make public their conclusions and reasons, collective decision making
can help reduce bias and error and increase the chance of rational decision
making, and allow time for circumstances and opinions to change (Williams
173). After creating the IRBs, the National Commission was no longer needed
and was disbanded.
Formation of Internal Review Boards (IRB)
Reasons for developing this specific system
The National Commission primarily decided to create local review boards
because the research community was ahead of public demand, regulating itself
before others did so. Therefore, this gave a guideline to begin with as
well as to improve. The National Commissions regulators thought that by
making the review board local, the penalties of regulation would be minimized.
Secondly, regulators presumed that IRBs would almost always operate within
a university teaching hospital where a shared commitment to the ideal of
good science would far outweigh any tendency for persons to trade favors
or elevate concerns for the financial viability of the institution above
their loyalty to the integrity of science or the well-being of subjects.
Third, the designers of the IRB system expected that the subjects themselves
were likely to be suspicious about human experimentation, adopting a cautious,
self-protective stand against involvement (Edgar 499). These factors formed
the premise of the IRBs formation.
Implementation
Once the IRBs were formed, they were left to their own devices. They encountered
two major problems: being able to differentiate between experimentation
and treatment and recognizing the correct way to obtain consent from clinical
research patients. These initial problems are still being worked out. The
IRBs have made great improvements in these areas of debate within both the
research and medical communities.
Conceptual Problems Encountered by IRBs
Differentiating between experiment and treatment
in medical studies
Historically, medical treatments have long been distinguished from experiments.
The term experiment embodies societal ambivalence about what is new about
medicine. Our society both embraces innovation and recoils from it at once.
New AIDS drugs, new cancer treatments, prenatal surgery, gene therapy, and
other examples repeatedly raise questions about when and how new technologies
should be made available, who should have access to them, and who should
pay for them. Most often, those questions are cast in terms of discerning
whether what is new is experimental or therapeutic.
The big question, then, is What marks a medical technology as experimental
rather than standard procedure? Nancy M. P. King suggests that there are
three principal contexts in which the designation experimental is currently
applied to medical technology and ultimately controlled. These include medical
malpractice, reimbursement, and research regulation. In medical malpractice,
distinguishing between experimentation and therapy determines whether injured
patients have been treated appropriately and provided with sufficient information
about their treatment. In the context of insurance reimbursement, the choice
of label determines whether an insurance plan will pay for a procedure.
The federal regulations governing research with human subjects contain a
definition that determines whether federal oversight is necessary (7).
Before the twentieth century, the practice of medicine was not organized
into the powerful, self-regulating, scientific profession recognized today.
It was not until the professions power and reputation had grown considerably
that the restraints of medical progress came to be a concern of the people
and eventually the courts. Cases raising the question of experimentation
in the modern era generally apply the standards of medical malpractice and
of informed consent. Upon review, the only thing that is clear from the
cases about the employment of the term experimental in the context of malpractice
is that it is linked to avoidable injury to patients.
Insurers and other third-party payers have attempted to define experimental
in the reimbursement context with a different object in mind: the limitation
of their payment obligations. Treatment ordered for a patient by a physician
is almost always paid for by someone else: a Blue Cross/Blue Shield plan,
HMO, Medicare or other plans. The primary coverage criterion for these plans
is often whether the treatment ordered is reasonable and necessary. Insurers
are increasingly attempting to curb their responsibility to pay for extremely
costly treatments that are unlikely to succeed by seeking to apply more
scientific definitions and standards of acceptability (King 8). This system
is a good check, however, desperate patients argue that technology assessment
takes too long and that is not fair to have to wait in the face of a life-threatening
illness.
The third setting in which the attempt is made to distinguish experiment
from treatment is governmental regulations. King says that the key to distinguishing
between research and treatment in this context has been held to be the physicians
intent regarding the activities in question (9). The National Commissions
Belmont Report defined medical practice as interventions . . . designed
solely to enhance the well-being of an individual patient . . . that have
a reasonable expectation of success (9). Research was then defined as an
activity designed to test a hypothesis, permit conclusions to be drawn,
and thereby to develop or contribute to generalizable knowledge (9).
Given the same example, decision makers in the three settings might well
draw different conclusions about where the line between experimentation
and treatment should be drawn. This could present some serious problems.
However, this was the problem that the National Commission tried to eradicate
with the integration of IRBs. IRBs are the main decision maker in most instances,
although, a few cases are ultimately decided by one of the three contexts.
The IRBs influence is usually acknowledged and considered.
Obtaining consent from potential human research
subjects
Another major problem that is still being debated by IRBs is the correct
pathway to obtain a patients consent in a clinical research project. Clinical
research is necessary to establish the safety and efficacy of a therapy.
Clinical testing of a new drug, operation, therapy, or any new advancement
in medical technology is required by the National Institute of Health (NIH)
before a product license for that treatment can be given. However, as the
treatment is being tested for safety and efficacy, patients taking part
will be put at risk of unknown side-effects and may also be randomized to
receive either the unproven drug or a placebo which is called the randomized
controlled trial (RCT). RCTs are extremely important in medical research
since it gives the best method of obtaining unbiased results.
The question is: How do we protect the patient in an RCT? By far the strongest
protection for the patient is her or his consent. Consent is an autonomous
authorization by one person to permit another person to carry out an agreed
procedure which affects the subject (Hewlett 233). By attaining consent
the researchers respect the patients wishes, enable them to be self-governing,
and uphold the principle of respect for persons. Four elements must be present
for consent to be morally acceptable: competence, information, understanding
of that information, and voluntariness.
All four of these elements must be observed before consent can be ascertained
from the patient. A person is considered competent if and only if that person
can make reasonable decisions based on rational reasons (Hewlett 233). The
information presented to the patient must be sufficient and unbiased, such
that a substantially autonomous decision can be made. It is the responsibility
of the health care professionals to ensure that the patient understands
the proposed research. For a patients consent to be adequately voluntary,
two factors must be fulfilled: the absence of controlling influences and
the ability to choose one of at least two options.
The first three elements of consent have been widely researched and debated
over the past fifteen years but little work has been done on the fourth
element, voluntariness. This is usually the most seriously threatened of
the four in clinical research. Unlike healthy volunteers, many patients
invited to participate in clinical research have an illness. The fear of
IRBs is that the experience of illness (which may at times include pain,
disability, fear of deterioration or death) and the accompanying psychological
response (possibly depression, mourning, denial, anger, and anxiety) may
well reduce autonomy. IRBs are also concerned that patients might commit
to a treatment, despite being told it was unlicensed and was being tested
for safety, because they believe that the doctor would only suggest a treatment
that was in their best interest.
IRBs are now trying to reduce influences on consent to clinical research.
Areas in which IRBs are trying to reduce these influences include the doctor/patient
relationship (by using a patient advocate), selection of patients that are
able to understand the research, education of the researcher in the problem
areas of consent, and using easily understood information sheets describing
the research in detail.
Two recently publicized examples show the ethical problems associated with
not following just one of these elements when obtaining consent. The first
was in the 1940-50s when researchers subjected 131 ill-informed prison inmates
to nuclear radiation, in order to study its effect on human beings (Watson
14). In this example, the inmates (the patients) were not told of the risks.
It is also conjectured that their consent shortened the inmates sentences,
which represents an outside influence on the decision. In another study
involving schizophrenic patients, the subjects were not told the full extent
of the risks of participation (Willwerth 62). The schizophrenic patients
were not told that some of them might receive placebos instead of their
regulating drugs. Those patients that received placebos usually regressed
to previous conditions.
Track Record of IRBs
Problems concerning the structure of IRBs
With an understanding of the initial problems that the IRBs have had to
deal with concerning consent and the differentiation between experiment
and therapy, it can be seen that, while not perfect, the IRBs have made
headway in these areas and many other issues. However, other questions which
arise concern the IRBs living up to the ideal model envisioned by the National
Committee, and whether they are the best model for ethical review boards
in the future. As with most organizations, IRBs have not lived up to their
ideal conceptual model, and they are criticized as being inadequate for
the problems that lie ahead in the future.
Upon review of past records of IRBs, many scientists and bioethicists find
the IRBs inadequate to deal with future advances in the medical field. The
largest problem is that new medical technologies continue to move society
in totally new directions, with no systematic review of their desirability.
Each IRB might decide differently on the same case. Also, the proportion
of research that is industry funded, rather than government supported, has
increased dramatically. This diminishes the power of the IRBs to do anything
since their power, the control of the money, has been taken away. In fact,
the academic center which served as a paradigm for the IRB is likely in
the future to lose what was once a near monopoly over research. Huge multistate
and international trials have begun to take over. With research becoming
more national, ethic reviews on the local level make little sense (Edgar
501).
Potential solutions to these problems
If the old paradigm no longer holds, what revisions should be made in public
policy? Most scientists and bioethicists agree that the IRB system has worked
reasonably well and that to dismantle it would be a mistake. However, where
do IRBs go from here? One current suggestion is the establishment of a super
committee or committees, charged at the minimum with a monitoring function
or at the maximum with the right to veto research deemed unacceptable. This
super committee would act as the Supreme Court within the bioethical review
board realm.
Edgar and Rothman suggest that there are three principal and interrelated
issues that must be addressed in the design of such a committee. The first
issue is whether to constitute one committee, endowing it with visibility
and prestige because of singularity, or several committees, distributing
responsibility among members selected for their particular expertise. Secondly,
it must be determined how expansive a committees jurisdiction should be:
whether it will be limited to reviewing funded grant proposals and issuing
advisory opinions, leaving the ultimate decisions to local IRBs and researchers;
or whether its approval will be required before research is undertaken.
The third issue involves deciding who should appoint such a committee and
what kind of staff it should have (503).
Formation of a new ethics board in the US
Within the last year at a White House ceremony, President Clinton described
the newly implemented National Bioethics Advisory Committee (NBAC). The
committees formation was mainly in response to the newly acquired knowledge
that the United States had sponsored radiation experiments during the Cold
War. President Clinton set up the committee with the goal of setting clear
ethical standards for human research so these atrocities would never happen
again (Centofanti 245). The influence of this new committee is uncertain
since they are still researching the many case studies that have been compiled
by the IRBs over the past fifteen years.
Conclusion
IRBs have set a good standard for ethical research from which to build upon.
However, with the ever advancing fields of research in neurobiology, genetic
therapy, and reproduction, it is time to take the superintendence of human
research to a different and more national level. Whether this change can
be accomplished by President Clintons National Bioethics Advisory Commission
within the current political climate is debatable. The necessity for such
a shift is not.
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