[Male Announcer] This country has always been
considered a melting pot. People from many nations and ethnic traditions
have come here. They brought with them varied religions, philosophies,
and concepts of right and wrong. Our nation reflects this diversity of peoples
and principles. We've created a government of consensus in
part to accommodate the diversity of ideas thrust into our melting pot. Some issues are resolved more easily than
others. Our history is replete with clashing values. For resolution, we turn to a variety of institutions:
government, the courts, the press, academia. Ideas have become institutions too: our Constitution
and Bill of Rights, a body of law and the various Western ethical and philosophical
traditions. These provide the principles, the ground rules
through which our problem-solving institutions can all agree to work. Research, too, is an institution. The principles which guide it, however, have
never been as well-defined as the bill of rights. In the early days, research relied mainly
on the integrity of the professional. Researchers invoked the benefit to society
and the need for progress to justify asking volunteers to bear research risks for all. By the early 1970s, various congressional
bodies had heard complaints. Basic protections weren't being given to people
participating in research. A frustrating paradox emerged. Researchers were making great progress in
relieving pain and suffering. Yet human research subjects in a few well-publicized
experiments clearly lacked protection. Everyone--Congress, researchers, and the public--
needed reassurance that abuses would be prevented. How would we deal with potential threats to
human values in new realms of investigation? Genetic research, behavior-modification techniques
and drugs, mood-altering drugs, and interventions such as organ transplants and artificial hearts? America was on the threshold of a biological
revolution. It had the potential to be as socially disruptive
as those sparked by Copernicus, Darwin, Freud, or the splitting of the atom. How would we protect certain groups of research
subjects that previously lacked adequate protect? The poor, disadvantaged, ethnic minorities,
prisoners, children, the mentally disabled, and the unborn? Congress was being called upon to draft new
legislation to cover problems which might arise at the frontiers of research. It responded by creating a national commission,
a forum which would come to grips with both the specific problems faced by researchers
and the need for a basic statement of ethical principles to guide new biomedical exploration. No matter what new directions science and
technology might take in the future, Congress wanted flexible review criteria established
that would protect human research subjects. They wanted to do for research what the Bill
of Rights was doing for so many other areas of human endeavor. The Commission began by studying populations
requiring special protection. Then it moved onto the broader congressional
mandate: Identify fundamental ethical principles which guide research. To do so, the commission paused for reflection
at a conference center outside Baltimore, the Belmont Center. The report that emerged in 1978, following
additional monthly deliberations, was known as The Belmont Report. It articulated three basic ethical principles
underlying all research involving human subjects. Actually, these principles have been part
of philosophical discourse and our Western heritage since the Greeks, but uniquely, The
Belmont Report tied each principle to concrete research applications. Today, a decade later, these eight pages continue
to be a standard reference for investigators and Institutional Review Boards. Of many possible principles, The Belmont Report
singled out respect for persons, beneficence, and justice. These three are comprehensive enough to capture
the ethical values inherent in good research. Respect for persons incorporates at least
two ethical convictions from our democratic heritage. Individuals should be treated as autonomous
agents. Autonomy means a person can think clearly
about personal goals. He or she is capable of making choices after
careful consideration of all information. [Woman] So the medicine is a medicine that
actually would slow down the hormones of puberty while you're still growing taller, and the
process of puberty would actually stop for a while you're taking the medicine. [Narrator] Subjects would be dealt with fairly
and openly. To deny someone autonomy is to deny them respect
as an individual. But some people do not have the capability
of self-determination, of autonomy, because of illness, mental disability, age, or immaturity. They require special protection, because they
may not be able to choose for themselves. But The Belmont Report does not stop with
this abstract principle. It explains a way to implement respect for
persons: informed consent. It then goes on to suggest several minimum
components of informed consent, such as information, comprehension, and voluntariness. [Woman #1] Okay, but usually we have-- when
we decide to have a young person go on a study, we have them actually sign the papers that
I sent you. Do you feel like you'd like to sign it now,
or would you rather wait till tomorrow when we go over it and see what other questions
there are? [Girl] Well, I could sign it now. [Woman #2] Well, we'll wait. Okay, we're gonna be back tomorrow anyway. So we'll talk— [Narrator] The Belmont Report lists detailed
consent criteria. Stating facts isn't enough. Is the information offered in the consent
process sufficient for people to decide whether they want to participate? Subjects must understand the extent of the
risk they are taking. They must know that participation is voluntary,
that they can withdraw from the research at any point if they choose. [Man] Maria, we have three problems in your
brain. [Woman speaking Spanish] [Narrator] But information, even complete
information, without comprehension is insufficient. Does the subject understand adequately? There are often cultural, language, and educational
factors that interfere with communication and the ability of the research subject to
understand. [Woman speaking Spanish] [Maria speaking Spanish] [Woman speaking Spanish] [Man] What is she asking? [Woman] She's asking-- she doesn't understand
why it's happening, this. [Narrator] Respecting the person means respecting
and dealing with the individual's ability to understand. An investigator must meet and deal with subjects
on their own terms. Consent must be free of coercion or undue
pressure. Belmont asks where does justifiable persuasion
end and undue pressure begin? [Man #1] The brain makes several substances
we call neurotransmitters. These are the chemicals that the brain cells
produce to use to communicate with one another. [Man #2] Mm-hmm. [Man #1] We know that in Alzheimer's Disease,
some of these neurotransmitters are deficient, and what we'd simply like to do is to put
some of them back and see if it improves the person's condition. [Narrator] When understanding is inherently
impaired, as with the mentally impaired, or not yet developed, respect requires giving
them the opportunity to the extent that they are able to choose whether or not to participate. The second principle is beneficence. Subjects place great trust in investigators. Following the principle of beneficence helps
validate that trust. [Man #1] The major hazard is that your thyroid
gland will take up large amounts of the injected radioactive iodine. This is prevented by the daily administration
of iodine-containing solution before and during the study. Okay, any questions at this point? [Young Man] Om, about what is the half-life
of the radioactive tracer? [Man #1] Okay - [Narrator] The Hippocratic maxim "Do no harm"
has long been a fundamental principle of medical ethics. However, avoiding harm requires learning what
is harmful. The process of obtaining this information
may expose people to risk. The Hippocratic Oath also requires physicians
to help or benefit their patients according to their best judgment. This is what Belmont calls beneficence. The problem posed by these imperatives is
to decide when it is justifiable to seek certain benefits despite the risks involved or when
the benefits should be foregone because of the risks. This principle has a parallel application:
assessment of risks and benefits. There are two steps in the assessment. Investigators and Institutional Review Boards
should first define the nature and scope of risks and benefits and then systematically
assess them, weighing risk against benefit. Ordinarily, quantitative techniques will not
be available to measure risks entailed by research procedures. However, as far as possible, there should
be systematic nonarbitrary analysis of the risks and benefits. Finally, The Belmont Report looks at justice. Who should receive the benefits of research? Who should bear its burdens? And for any research, how can we be sure the
risks are distributed equitably? During the 19thand early 20th centuries, the
burdens of serving as research subjects fell largely on poor ward patients. They often received good care, but private
patients were less frequently called upon. The burden was unequal. Today our sense of justice makes us scrutinize
the selection of research subjects more carefully. Are some classes of patients-- welfare recipients,
minorities, or inmates of institutions-- being selected simply for easy availability and
manipulation rather than for reasons related to the research? The Belmont Report has been and continues
to be widely read. Researchers and members of Institutional Review
Boards should consider it a required reference work. How are the Belmont principles applied? How are they inherent in good research? For an answer, we go back to the early 1970s. Researchers were keenly aware of the need
to prove the efficacy of new drugs or procedures. Social responsibility demanded it. Randomized clinical trials were the method
of proof. At NIH, Dr. Carl Kupfer was preparing to test
a widely used but unproven eye treatment. [Kupfer] Only by doing a randomized-control
clinical trial can we determine in a very scientifically valid way and without any equivocation,
whether a particular treatment modality whether it's a new drug or a new surgical intervention
is a benefit to the patient. [Narrator] Diabetics frequently experience
small hemorrhages in the retinas of both eyes as a consequence of diabetic retinopathy. With the availability xenon arc and argon
laser energy sources, ophthalmologists had experimentally burned away this damaged tissue. The procedure was call photocoagulation and
was believed to slow or stop the progress toward blindness. But the efficacy of the treatment had never
been shown. In fact, photocoagulation conceivably could
damage the eye. In a randomized clinical trial, researchers
set out to validate the procedure. Dr. Frederick Ferris was one of the investigators. [Ferris] And it occurred to us that perhaps
you could have your cake and eat it too, in a sense, particularly from the patient’s
point of view, because we weren't sure whether the new treatment was better than no treatment
at all, we weren't sure what all the risks of treatment were, and we weren't sure what
all the benefits of treatment were. With this kind of design, where we could do
one treatment in one eye and the other treatment in the other eye, I think we were aware that
we really could provide for the patient some of both, a little bit of having your cake
and eating it too, because if it was true that the new treatment was harmful, well,
we wouldn't harm both eyes. If it was true that it was beneficial, at
least one eye would have received the benefit of photocoagulation. And therefore, whichever turned out to be
better, the patient would have received the better treatment. [Narrator] Society has the right to require
that a particular procedure be shown to do good-- beneficence, in the language of Belmont. Dr. Kupfer and his fellow researchers sought
to demonstrate whether or not photocoagulation is beneficial. Beneficence also requires that research subjects
be unharmed by their participation. Do no harm. These two moral imperatives are not opposites
or mutually exclusive. They're simply parallel issues, both of which
must be addressed. The team also was concerned with the respect
for persons through the process of informed consent. [Kupfer] Because in a sense, the informed
consent is inextricably bound up with the ethical question. If a physician can honestly sit down with
the patient and explain the informed consent and all the potential benefits and all the
potential adverse effects of the treatment and be convincing to the patient, that means,
first of all, the physician believes this, and secondly, only if it is truly ethical
and the physician feels that in his own heart can he convince the patient to go ahead and
enroll in such a study. [Man#3] That could be of a serious nature. What happens in diabetic patients is that
the tiny little capillaries, the little blood vessels that nourish the retina get narrowed
down. [Narrator] The study was designed to follow
patients for up to five years. They returned for examination every few months. Consent needed to be an ongoing process. [Man #3] You've had a small hemorrhage in
your untreated right eye. It's relatively small. I can't tell for sure where it's coming from,
but I suspect it may be from the new blood vessels on the nerve of vision. I think it will probably clear in a couple
of months, but the long-range outlook will depend upon how many more hemorrhages you
have. [Woman #3] Would you treat my right eye now
or sometime later? [Man #3] Well, the doctors that are monitoring
the results of this study tell us that, to date, there’s no clear evidence that treatment
is either beneficial or harmful. So I think we should stick to our original
decision to just treat your left eye and not do any treatment to your right eye. [Ferris] We told them that as data accumulated
in the trial, it may become evident that one treatment was better than the other, or treatment
was better than no treatment. And we told them that as soon as that information
became available and it was clear-cut that one was better than the other, we would inform
them and we would do whatever was appropriate with the other eye. If it had turned out that treatment was dangerous,
of course, we wouldn't have done anything to the other eye. As it turned out, about a little over two
years into this study, it became clear that treatment was better than no treatment. [Narrator] Of course, central to the study's
capacity to keep the research subject informed was an ongoing data-monitoring program. [Kupfer] Another aspect of ethics which I
think is terribly important and is built into every clinical trial is the use of a data
and safety monitoring committee. This is a group of individuals who are knowledgeable
but outside the study who look at the data every four months, six months, eight months,
depending on how that data is coming in, and decides when that clinical trial should be
stopped either because there’s a clear benefit from the intervention or because there may
some very serious adverse effects or when the protocol might be changed to accommodate
some new development. [Man] Watch the red light, Jen. [Narrator] Seeing the Belmont principles as
a legalistic test for compliances or noncompliance is to misdirect them. Rather, they are intellectual tools the IRB
can use to articulate issues and then adjust the protocol for the greatest possible protection
of the research subject. [Woman #4] Now, it's important that we understand
some of the things that happened that evening. And what I want to ask you is— [Narrator] Social problems also area fertile
area for research. Our next case study looks at how the Belmont
principles can be applied to a one-year longitudinal study of anxiety reactions to sexual assault. Victims of social violence are the source
of much valuable information, but researchers must take great care to minimize the additional
stress caused by research questions. [Woman #5] So they've got intervene in the
first two, so they’ve got to ask everyone — [Narrator] These two IRB members have been
invited to review a proposal for the study conducted by a university psychology department. Two groups will be interviewed: women selected
through a hospital emergency room sexual assault center and a comparison group using the emergency
room for primary medical care. Even at this screening stage, care must be
taken to respect the potential research subject. The women from the assault center will know
why they are being asked personal questions, but what about the women being recruited for
the comparison group? They, too, are being asked very personal questions
to screen out those who’ve experienced social violence. How are they protected? [Woman #5] There's some pretty explicit questions
in there, and if the researcher doesn’t know, that's asking questions and doesn't
know that a person is a rape victim, all of a sudden, the person may begin reacting to
some of the questions and getting upset by them. [Woman #4] Well, they're going to have to
build in some procedures for stopping the interview, for handling any kind of discomfort
that comes up during the interview, but they're also going to have to provide some follow-up
care, not treatment, but some kind of follow-up procedures for these people who might get
upset by discussing things that happened in the past. [Narrator] A person's response to probing
questions can't always be predicted. The researcher's questions may trigger emotional
stress in the individual. Not only must interviewers be trained to be
sensitive to the feelings and circumstances of both victims and the comparison group,
they also must know how to safeguard confidentiality. [Woman #4] That anything said to the researcher
will not in fact go back to either the rape crisis center or to the hospital. The best way for this person to accomplish
that would probably be to actually be doing the interview somewhere other than hospital
property. That would reemphasize to the patients or
to the clients that their records are separate. So at this point, he’s proposing to sit--
she's proposing to sit in a room in the hospital, and I think that we should recommend that
the research interviews be done somewhere else. [Woman #5] You know, the other thing I noticed
that really concerned me a lot is that the consent form is filled with, like, promissory
notes. "We guarantee full confidentiality," and the
like, but they don't really outline what the protections are. It's simply a take it on faith, and I think
the researcher needs to think through more than just good intent, the actual procedures. Now, that would be one example – where it
would--where the interviews would be held and who would have access to the information. [Narrator] Many questions need to be asked
about the entire consent process. There are several steps involved. This study lasts a year. Each visit by the subject requires consent. [Woman #5] You know, something else I thought
about when you mentioned a person being able to-- and to be told ahead of time that they
can withdraw or not answer any questions, you should probably also-- which they don't
have in their protocol-- have a multistage consent. Even though--each time that you don't assume
that the first time that the person gives consent, until they actually know what the
questions are, it's very difficult to know exactly what you're giving consent to, and
it would be good to make sure that, each time, you reexplain what it is you're doing, and
explain each time, because they're going to forget over a period of three months since
the last time, that they can withdraw or can refuse to answer questions. [Narrator] The principles stated in The Belmont
Report apply to behavioral and social science research. They are a tool rather than absolutes. This program began with the idea that research
is taking its place as an institution in our society. It joins government, the family, academia,
and free speech as institutions that protect our values in the face of change. We made an analogy between ethical principles
and the Bill of Rights. Both are statements of principle which help
guide their respective institutions. The Belmont Report is one resource among many. It is applied to research issues along with
a host of other professional codes, statements of principle, and regulations. The Belmont principles stand apart, however,
because they have a flexibility that codes do not. Rather than setting forth rigid prohibitions,
the report encourages debate and careful consideration. IRB members and investigators are committed
to the rights of individuals, but determinations made by IRBs and investigators would be limited
if they relied only on their personal resources. The Belmont principles enlarge the debate. They encourage breadth and depth. The principles represent a consensus going
back to the Greeks. [Sabin] A scientist doing research in order
to solve problems of importance to human beings and the resolution of the unknown of human
disease has very high principles to begin with. And I've had to use human subjects during
the course of my career for getting many other kinds of answers, but there were two basic
principles. In the first place, can the answer be gotten
in any other way? And if the answer is no, then you must approach
the use of human subjects, volunteers. And the second question was, is it necessary? Is it important enough? Because if it is not important enough, I felt,
personally, there was never any justification to use volunteers. [Narrator] The concept of human dignity is
what inspires research. Disease of any sort is an offense against
dignity. Scientific advances, then, must be made with
no compromise to the dignity of research subjects. Good science and good ethics go hand in hand.
