THE BELMONT REPORT

Scientific research has produced substantial social benefits. It has also posed some troubling ethical questions. Public attention was drawn to these questions by reported abuses of human subjects in biomedical experiments, especially during the Second World War. During the Nuremberg War Crime Trials, the Nuremberg Code was drafted as a set of standards for judging physicians and scientists who had conducted biomedical experiments on concentration camp prisoners. This Code became the prototype of many later codes intended to assure that research involving human subjects would be carried out in an ethical manner.

The codes consist of rules, some general, others specific, that guide the investigators or the reviewers of research in their work. Such rules often are inadequate to cover complex situations; at times they come into conflict, and they are frequently difficult to interpret or apply. Broader ethical principles will provide a basis on which specific rules may be formulated, criticized and interpreted.

Three principles, or general prescriptive judgments, that are relevant to research involving human subjects are identified in this statement. Other principles may also be relevant. These three are comprehensive, however, and are stated at a level of generalization that should assist scientists, subjects, reviewers and interested citizens to understand the ethical issues inherent in research involving human subjects. These principles cannot always be applied, so as to resolve beyond dispute particular ethical problems. The objective is to provide an analytical framework that will guide the resolution of ethical problems arising from research involving human subjects.

This statement consists of a distinction between research and practice, a discussion of the three basic ethical principles, and remarks about the application of these principles.  

A. Boundaries Between Practice and Research

It is important to distinguish between biomedical and behavioral research, on the one hand, and the practice of accepted therapy on the other, in order to know what activities ought to undergo review for the protection of human subjects of research. The distinction between research and practice is blurred, partly because both often occur together (as in research designed to evaluate a therapy), and partly because notable departures from standard practice are often called "experimental", when the terms "experimental" and "research" are not carefully defined.

For the most part, the term "practice" refers to interventions that are designed solely to enhance the well-being of an
individual patient or client and that have a reasonable expectation of success. The purpose of medical or behavioral
practice is to provide diagnosis, preventive treatment or therapy to particular individuals. By contrast, the term "research" designates an activity designed to test an hypothesis, permit conclusions to be drawn, and thereby to develop or contribute to generalizable knowledge (expressed, for example, in theories, principles, and statements of relationships).

Research is usually described in a formal protocol that sets forth an objective and a set of procedures designed to reach that objective.

When a clinician departs in a significant way from standard or accepted practice, the innovation does not, in and of itself, constitute research. The fact that a procedure is "experimental" in the sense of new, untested or different, does not automatically place it in the category of research. Radically new procedures of this description should, however, be made the object of formal research at an early stage, in order to determine whether they are safe and effective. Thus, it is the responsibility of medical practice committees, for example, to insist that a major innovation be incorporated into a formal research project.

Research and practice may be carried on together, when research is designed to evaluate the safety and efficacy of a therapy. This need not cause any confusion regarding whether or not the activity requires review; the general rule is, that if there is any element of research in an activity, that activity should undergo review for the protection of human subjects.

B. Basic Ethical Principles

The expression "basic ethical principles" refers to those general judgments that serve as a basic justification for the many particular ethical prescriptions and evaluations of human actions. Three basic principles, among those generally accepted in our cultural tradition, are particularly relevant to the ethics of research involving human subjects: the principles of respect for persons, beneficence and justice.

1.Respect for Persons

Respect for persons incorporates at least two ethical convictions: first, that individuals should be treated as
autonomous agents, and second, that persons with diminished autonomy are entitled to protection. The principle of
respect for persons thus divides into two separate moral requirements: the requirement to acknowledge autonomy,
and the requirement to protect those with diminished autonomy.

An autonomous person is an individual capable of deliberation about personal goals, and of acting under the
direction of such deliberation. To respect autonomy is to give weight to autonomous persons' considered opinions
and choices, while refraining from obstructing their actions, unless they are clearly detrimental to others. To show
lack of respect for an autonomous agent is to repudiate that person's considered judgments, to deny an individual
the freedom to act on those considered judgments, or to withhold information necessary to make a considered
judgment, when there are no compelling reasons to do so.

However, not every human being is capable of self-determination. The capacity for self-determination matures
during an individual's life, and some individuals lose this capacity wholly or in part, because of illness, mental
disability, or circumstances that severely restrict liberty. Respect for the immature and the incapacitated may require
protecting them as they mature or while they are incapacitated.

Some persons are in need of extensive protection, even to the point of excluding them from activities which may
harm them; other persons require little protection beyond making sure they undertake activities freely and with
awareness of possible adverse consequences. The extent of protection afforded should depend upon the risk of
harm, and the likelihood of benefit. The judgment that any individual lacks autonomy should be periodically
reevaluated, and will vary in different situations.

In most cases of research involving human subjects, respect for persons demands that subjects enter into the
research voluntarily and with adequate information. In some situations, however, application of the principle is not
obvious. The involvement of prisoners as subjects of research provides an instructive example. On the one hand, it
would seem that the principle of respect for persons requires that prisoners not be deprived of the opportunity to
volunteer for research. On the other hand, under prison conditions they may be subtly coerced or unduly influenced
to engage in research activities, for which they would not otherwise volunteer. Respect for persons would then
dictate that prisoners be protected. Whether to allow prisoners to "volunteer" or to "protect" them presents a
dilemma. Respecting persons, in most hard cases, is often a matter of balancing competing claims urged by the
principle of respect itself.

2.Beneficence

Persons are treated in an ethical manner, not only by respecting their decisions and protecting them from harm, but
also by making efforts to secure their well-being. Such treatment falls under the principle of beneficence. The term
"beneficence" is often understood to cover acts of kindness or charity that go beyond strict obligation. In this
document, beneficence is understood in a stronger sense, as an obligation. Two general rules have been formulated
as complementary expressions of beneficent actions in this sense: (1) do not harm; and (2) maximize possible
benefits, and minimize possible harms.

The Hippocratic maxim "do no harm" has long been a fundamental principle of medical ethics. Claude Bernard
extended it to the realm of research, saying that one should not injure one person, regardless of the benefits that
might come to others. However, even avoiding harm requires learning what is harmful; and, in the process of
obtaining this information, persons may be exposed to risk of harm. Further, the Hippocratic Oath requires
physicians to benefit their patients "according to their best judgment". Learning what will in fact benefit may require
exposing persons to risk. The problem posed by these imperatives is to decide when it is justifiable to seek certain
benefits despite the risks involved, and when the benefits should be foregone because of the risks.

The obligations of beneficence affect both individual investigators and society at large, because they extend both to
particular research projects and to the entire enterprise of research. In the case of particular projects, investigators
and members of their institutions are obliged to give forethought to the maximization of benefits and the reduction of
risk that might occur from the research investigation. In the case of scientific research in general, members of the
larger society are obliged to recognize the longer term benefits and risks that may result from the improvement of
knowledge, and from the development of novel medical, psychotherapeutic, and social procedures.

The principle of beneficence often occupies a well-defined, justifying role in many areas of research involving
human subjects. An example is found in research involving children. Effective ways of treating childhood diseases
and fostering healthy development are benefits that serve to justify research involving children --even when
individual research subjects are not direct beneficiaries. Research also makes it possible to avoid the harm that may
result from the application of previously accepted routine practices that, on closer investigation, turn out to be
dangerous. But the role of the principle of beneficence is not always so unambiguous. A difficult ethical problem
remains, for example, about research that presents more than minimal risk, without immediate prospect of direct
benefit to the children involved. Some have argued that such research is inadmissible, while others have pointed
out, that this limit would rule out much research promising great benefit to children in the future. Here again, as with
all hard cases, the different claims covered by the principle of beneficence may come into conflict and force difficult
choices.

3.Justice

Who ought to receive the benefits of research and bear its burdens? This is a question of justice, in the sense of
"fairness in distribution" or "what is deserved". An injustice occurs, when some benefit to which a person is entitled
is denied without good reason, or when some burden is imposed unduly. Another way of conceiving the principle
of justice is that, equals ought to be treated equally. However, this statement requires explication. Who is equal and
who is unequal? What considerations justify departure from equal distribution? Almost all commentators allow that
distinctions based on experience, age, deprivation, competence, merit and position do sometimes constitute criteria
justifying differential treatment for certain purposes. It is necessary, then, to explain in what respects people should
be treated equally. There are several widely accepted formulations of just ways to distribute burdens and benefits.
Each formulation mentions some relevant property, on the basis of which burdens and benefits should be
distributed. These formulations are (1) to each person an equal share, (2) to each person according to individual
need, (3) to each person according to individual effort, (4) to each person according to societal contribution, and
(5) to each person according to merit.

Questions of justice have long been associated with social practices, such as punishment, taxation and political
representation. Until recently, these questions have not generally been associated with scientific research. However,
they are foreshadowed, even in the earliest reflections on the ethics of research involving human subjects. For
example, during the 19th and early 20th centuries, the burdens of serving as research subjects fell largely upon poor
ward patients, while the benefits of improved medical care flowed primarily to private patients. Subsequently, the
exploitation of unwilling prisoners as research subjects in Nazi concentration camps was condemned as a
particularly vagrant injustice. In this country, in the 1940's, the Tuskegee syphilis study used disadvantaged, rural
black men to study the untreated course of a disease that is by no means confined to that population. These
subjects were deprived of demonstrably effective treatment in order not to interrupt the project, long after such
treatment became generally available.

Against this historical background, it can be seen how conceptions of justice are relevant to research involving
human subjects. For example, the selection of research subjects needs to be scrutinized in order to determine
whether some classes (e.g., welfare patients, particular racial and ethnic minorities, or persons confined to
institutions) are being systematically selected, simply because of their easy availability, their compromised position,
or their manipulability, rather than for reasons directly related to the problem being studied. Finally, whenever
research supported by public funds leads to the development of therapeutic devices and procedures, justice
demands both that these not provide advantages only to those who can afford them, and that such research should
not unduly involve persons from groups unlikely to be among the beneficiaries of subsequent applications of the
research.

C. Applications

Applications of the general principles to the conduct of research leads to consideration of the following requirements: informed consent, risk / benefit assessment, and the selection of subjects of research.

1.Informed Consent

Respect for persons requires that subjects, to the degree that they are capable, be given the opportunity to choose
what shall or shall not happen to them. This opportunity is provided, when adequate standards for informed
consent are satisfied.

While the importance of informed consent is unquestioned, controversy prevails over the nature and possibility of
an informed consent. Nonetheless, there is widespread agreement that the consent process can be analyzed as
containing three elements: information, comprehension and voluntariness.

Information

Most codes of research establish specific items for disclosure, intended to assure that subjects are given
sufficient information. These items generally include: the research procedure, their purposes, risks and
anticipated benefits, alternative procedures (where therapy is involved), and a statement offering the subject
the opportunity to ask questions and to withdraw at any time from the research. Additional items have been
proposed, including how subjects are selected, the person responsible for the research, etc.

However, a simple listing of items does not answer the question of what the standard should be for judging
how much and what sort of information should be provided. One standard frequently invoked in medical
practice, namely the information commonly provided by practitioners in the field or in the locale, is
inadequate, since research takes place precisely when a common understanding does not exist. Another
standard, currently popular in malpractice law, requires the practitioner to reveal the information that
reasonable persons would wish to know in order to make a decision regarding their care. This, too, seems
insufficient, since the research subject, being in essence a volunteer, may wish to know considerably more
about risks gratuitously undertaken than do patients who deliver themselves into the hand of a clinician for
needed care. It may be, that a standard of "the reasonable volunteer" should be proposed: the extent and
nature of information should be such that persons, knowing that the procedure is neither necessary for their
care nor perhaps fully understood, can decide whether they wish to participate in the furthering of
knowledge. Even when some direct benefit to them is anticipated, the subjects should understand clearly the
range of risk, and the voluntary nature of participation.

A special problem of consent arises, where informing subjects of some pertinent aspect of the research is
likely to impair the validity of the research. In many cases, it is sufficient to indicate to subjects that they are
being invited to participate in research, of which some features will not be revealed until the research is
concluded. In all cases of research involving incomplete disclosure, such research is justified, only if it is clear
that (1) incomplete disclosure is truly necessary to accomplish the goals of the research, (2) there are no
undisclosed risks to subjects that are more than minimal, and (3) there is an adequate plan for debriefing
subjects, when appropriate, and for dissemination of research results to them. Information about risks should
never be withheld for the purpose of eliciting the cooperation of subjects, and truthful answers should always
be given to direct questions about the research. Care should be taken to distinguish cases, in which
disclosure would destroy or invalidate the research, from cases in which disclosure would simply
inconvenience the investigator.

Comprehension

The manner and context, in which information is conveyed is as important as the information itself. For
example, presenting information in a disorganized and rapid fashion, allowing too little time for consideration,
or curtailing opportunities for questioning, all may adversely affect a subject's ability to make an informed
choice.

Because the subject's ability to understand is a function of intelligence, rationality, maturity and language, it is
necessary to adapt the presentation of the information to the subject's capacities. Investigators are
responsible for ascertaining that the subject has comprehended the information. While there is always an
obligation to ascertain that the information about risk to subjects is complete and adequately comprehended,
when the risks are more serious, that obligation increases. On occasion, it may be suitable to give some oral
or written tests of comprehension.

Special provision may need to be made, when comprehension is severely limited --for example, by
conditions of immaturity or mental disability. Each class of subjects that one might consider as incompetent
(e.g., infants and young children, mentally disabled patients, the terminally ill, and the comatose) should be
considered on its own terms. Even for these persons, however, respect requires giving them the opportunity
to choose, to the extent they are able, whether or not to participate in research. The objections of these
subjects to involvement should be honored, unless the research entails providing them a therapy unavailable
elsewhere. Respect for persons also requires seeking the permission of other parties in order to protect the
subjects from harm. Such persons are thus respected, both by acknowledging their own wishes, and by the
use of third parties to protect them from harm.

The third parties chosen should be those, who are most likely to understand the incompetent subject's
situation, and to act in that person's best interest. The person authorized to act on behalf of the subject
should be given an opportunity to observe the research, as it proceeds, in order to be able to withdraw the
subject from the research, if such action appears in the subject's best interest.

Voluntariness

An agreement to participate in research constitutes a valid consent, only if voluntarily given. This element of
informed consent requires conditions free of coercion and undue influence. Coercion occurs when an overt
threat of harm is intentionally presented by one person to another, in order to obtain compliance. Undue
influence, by contrast, occurs through an offer of an excessive, unwarranted, inappropriate or improper
reward or other overture, in order to obtain compliance. Also, inducements that would ordinarily be
acceptable may become undue influences, if the subject is especially vulnerable.

Unjustifiable pressures usually occur, when persons in positions of authority or commanding influence
--especially where possible sanctions are involved-- urge a course of action for a subject. A continuum of
such influencing factors exists, however, and it is impossible to state precisely, where justifiable persuasion
ends and undue influence begins. But undue influence would include actions, such as manipulating a person's
choice through the controlling influence of a close relative, and threatening to withdraw health services to
which an individual would otherwise be entitled.

2.Assessment of Risks and Benefits

The assessment of risks and benefits requires a careful arrayal of relevant data, including, in some cases, alternative
ways of obtaining the benefits sought in the research. Thus, the assessment presents both an opportunity and a
responsibility to gather systematic and comprehensive information about proposed research. For the investigator, it
is a means to examine whether the proposed research is properly designed. For a review committee, it is a method
for determining whether the risks that will be presented to subjects are justified. For prospective subjects, the
assessment will assist the determination whether or not to participate.

The Nature and Scope of Risks and Benefits

The requirement that research be justified on the basis of a favorable risk / benefit assessment, bears a close
relation to the principle of beneficence, just as the moral requirement that informed consent be obtained is
derived primarily from the principle of respect for persons.

The term "risk" refers to a possibility that harm may occur. However, when expressions such as "small risk"
or "high risk" are used, they usually refer (often ambiguously) both to the chance (probability) of experiencing
a harm, and the severity (magnitude) of the envisioned harm.

The term "benefit" is used in the research context to refer to something of positive value related to health or
welfare. Unlike "risk", "benefit" is not a term that expresses probabilities. Risk is properly contrasted to
probability of benefits, and benefits are properly contrasted with harms rather than risks of harm.
Accordingly, so-called risk / benefit assessments are concerned with the probabilities and magnitudes of
possible harms, and anticipated benefits. Many kinds of possible harms and benefits need to be taken into
account. There are, for example, risks of psychological harm, physical harm, legal harm, social harm and
economic harm, and the corresponding benefits. While the most likely types of harms to research subjects
are those of psychological or physical pain or injury, other possible kinds should not be overlooked.

Risks and benefits of research may affect the individual subjects, the families of the individual subjects, and
society at large (or special groups of subjects in society). Previous codes and Federal regulations have
required that risks to subjects be outweighed by the sum of both the anticipated benefit to the subject, if any,
and the anticipated benefit to society in the form of knowledge to be gained from the research. In balancing
these different elements, the risks and benefits affecting the immediate research subject will normally carry
special weight. On the other hand, interests, other than those of the subject, may on some occasions be
sufficient by themselves to justify the risks involved in the research, so long as the subjects' rights have been
protected. Beneficence thus requires that we protect against risk of harm to subjects, and also that we be
concerned about the loss of the substantial benefits that might be gained from research.

The Systematic Assessment of Risks and Benefits

It is commonly said that benefits and risks must be "balanced", and shown to be "in a favorable ratio". The
metaphorical character of these terms draws attention to the difficulty of making precise judgments. Only on
rare occasions will quantitative techniques be available for the scrutiny of research protocols. However, the
idea of systematic, nonarbitrary analysis of risks and benefits should be emulated insofar as possible. This
ideal requires those making decisions about the justifiability of research to be thorough in the accumulation
and assessment of information about all aspects of the research, and to consider alternatives systematically.
This procedure renders the assessment of research more rigorous and precise, while making communication
between review board members and investigators less subject to misinterpretation, misinformation and
conflicting judgments. Thus, there should first be a determination of the validity of the presuppositions of the
research; then the nature, probability and magnitude of risk should be distinguished, with as much clarity as
possible. The method of ascertaining risks should be explicit, especially where there is no alternative to the
use of such vague categories as small or slight risk. It should also be determined whether an investigator's
estimates of the probability of harm or benefits are reasonable, as judged by known facts or other available
studies.

Finally, assessment of the justifiability of research should reflect at least the following considerations: (i)
Brutal or inhumane treatment of human subjects is never morally justified. (ii) Risks should be reduced to
those necessary to achieve the research objective. It should be determined whether it is in fact necessary to
use human subjects at all. Risk can perhaps never be entirely eliminated, but it can often be reduced by
careful attention to alternative procedures. (iii) When research involves significant risk of serious impairment,
review committees should be extraordinarily insistent on the justification of the risk (looking usually to the
likelihood of benefit to the subject --or, in some rare cases, to the manifest voluntariness of the
participation). (iv) When vulnerable populations are involved in research, the appropriateness of involving
them should itself be demonstrated. A number of variables go into such judgments, including the nature and
degree of risk, the condition of the particular population involved, and the nature and level of the anticipated
benefits. (v) Relevant risks and benefits must be thoroughly arrayed in documents and procedures used in
the informed consent process.

3.Selection of Subjects

Just as the principle of respect for persons finds expression in the requirements for consent, and the principle of
beneficence in risk / benefit assessment, the principle of justice gives rise to moral requirements that there be fair
procedures and outcomes in the selection of research subjects.

Justice is relevant to the selection of subjects of research at two levels: the social and the individual. Individual
justice in the selection of subjects would require that researchers exhibit fairness: thus, they should not offer
potentially beneficial research only to some patients, who are in their favor, or select only "undesirable" persons for
risky research. Social justice requires that distinction be drawn between classes of subjects that ought, and ought
not, to participate in any particular kind of research, based on the ability of members of that class to bear burdens,
and on the appropriateness of placing further burdens on already burdened persons. Thus, it can be considered a
matter of social justice, that there is an order of preference in the selection of classes of subjects (e.g., adults before
children), and that some classes of potential subjects (e.g., the institutionalized mentally infirm or prisoners) may be
involved as research subjects, if at all, only on certain conditions.

Injustice may appear in the selection of subjects, even if individual subjects are selected fairly by investigators, and
treated fairly in the course of research. Thus, injustice arises from social, racial, sexual and cultural biases
institutionalized in society. Thus, even if individual researchers are treating their research subjects fairly, and even if
institutional review boards are taking care to assure that subjects are selected fairly within a particular institution,
unjust social patterns may nevertheless appear in the overall distribution of the burdens and benefits of research.
Although individual institutions or investigators may not be able to resolve a problem that is pervasive in their social
setting, they can consider distributive justice in selecting research subjects.

Some populations, especially institutionalized ones, are already burdened in many ways by their infirmities and
environments. When research is proposed that involves risks and does not include a therapeutic component, other
less burdened classes of persons should be called upon first to accept these risks of research, except where the
research is directly related to the specific conditions of the class involved. Also, even though public funds for
research may often flow in the same directions as public funds for health care, it seems unfair that populations
dependent on public health care constitute a pool of preferred research subjects, if more advantaged populations
are likely to be the recipients of the benefits.

One special instance of injustice results from the involvement of vulnerable subjects. Certain groups, such as racial
minorities, the economically disadvantaged, the very sick, and the institutionalized, may continually be sought as
research subjects, owing to their ready availability in settings, where research is conducted. Given their dependent
status and their frequently compromised capacity for free consent, they should be protected against the danger of
being involved in research solely for administrative convenience, or because they are easy to manipulate as a result
of their illness or socioeconomic condition.