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The Belmont Report

Office of the Secretary =

Ethical=20 Principles and Guidelines for the Protection of Human
Subjects of = Research=20

The National Commission for the Protection of Human Subjects =
of=20 Biomedical and Behavioral Research

April 18, = 1979

AGENCY: Department of Health, Education, and Welfare.=20

ACTION: Notice of Report for Public Comment.=20

SUMMARY: On July 12, 1974, the National Research Act (Pub. L. = 93-348)=20 was signed into law, there-by creating the National Commission for the=20 Protection of Human Subjects of Biomedical and Behavioral Research. One = of the=20 charges to the Commission was to identify the basic ethical principles = that=20 should underlie the conduct of biomedical and behavioral research = involving=20 human subjects and to develop guidelines which should be followed to = assure that=20 such research is conducted in accordance with those principles. In = carrying out=20 the above, the Commission was directed to consider: (i) the = boundaries=20 between biomedical and behavioral research and the accepted and routine = practice=20 of medicine, (ii) the role of assessment of risk-benefit criteria = in the=20 determination of the appropriateness of research involving human = subjects,=20 (iii) appropriate guidelines for the selection of human subjects = for=20 participation in such research and (iv) the nature and definition = of=20 informed consent in various research settings.=20

The Belmont Report attempts to summarize the basic ethical principles = identified by the Commission in the course of its deliberations. It is = the=20 outgrowth of an intensive four-day period of discussions that were held = in=20 February 1976 at the Smithsonian Institution's Belmont Conference Center = supplemented by the monthly deliberations of the Commission that were = held over=20 a period of nearly four years. It is a statement of basic ethical = principles and=20 guidelines that should assist in resolving the ethical problems that = surround=20 the conduct of research with human subjects. By publishing the Report in = the=20 Federal Register, and providing reprints upon request, the Secretary = intends=20 that it may be made readily available to scientists, members of = Institutional=20 Review Boards, and Federal employees. The two-volume Appendix, = containing the=20 lengthy reports of experts and specialists who assisted the Commission = in=20 fulfilling this part of its charge, is available as DHEW Publication No. = (OS)=20 78-0013 and No. (OS) 78-0014, for sale by the Superintendent of = Documents, U.S.=20 Government Printing Office, Washington, D.C. 20402.=20

Unlike most other reports of the Commission, the Belmont Report does = not make=20 specific recommendations for administrative action by the Secretary of = Health,=20 Education, and Welfare. Rather, the Commission recommended that the = Belmont=20 Report be adopted in its entirety, as a statement of the Department's = policy.=20 The Department requests public comment on this recommendation.

National Commission for the Protection of Human Subjects
of = Biomedical=20 and Behavioral Research

Members of the Commission

Kenneth John Ryan, M.D., Chairman, Chief of Staff, Boston = Hospital for=20 Women.=20
Joseph V. Brady, Ph.D., Professor of Behavioral Biology, Johns = Hopkins=20 University.=20
Robert E. Cooke, M.D., President, Medical College of = Pennsylvania.=20
Dorothy I. Height, President, National Council of Negro Women, = Inc.=20
Albert R. Jonsen, Ph.D., Associate Professor of Bioethics, = University=20 of California at San Francisco.=20
Patricia King, J.D., Associate Professor of Law, Georgetown = University=20 Law Center.=20
Karen Lebacqz, Ph.D., Associate Professor of Christian Ethics, = Pacific=20 School of Religion.=20
*** David W. Louisell, J.D., Professor of Law, University of = California=20 at Berkeley.=20
Donald W. Seldin, M.D., Professor and Chairman, Department of = Internal=20 Medicine, University of Texas at Dallas.=20
***Eliot Stellar, Ph.D., Provost of the University and = Professor of=20 Physiological Psychology, University of Pennsylvania.=20
*** Robert H. Turtle, LL.B., Attorney, VomBaur, Coburn, Simmons = &=20 Turtle, Washington, D.C.

*** Deceased.

Table of Contents


Ethical=20 Principles and Guidelines for Research Involving Human Subjects =
A.=20 Boundaries Between Practice and Research
B.=20 Basic Ethical Principles
1.=20 Respect for Persons=20
2.=20 Beneficence=20
3.=20 Justice
= C.=20 Applications
1.=20 Informed Consent=20
2.=20 Assessment of Risk and Benefits=20
3.=20 Selection of Subjects

Ethical Principles & Guidelines for = Research=20 Involving Human Subjects

Scientific research has produced substantial social benefits. It has = also=20 posed some troubling ethical questions. Public attention was drawn to = these=20 questions by reported abuses of human subjects in biomedical = experiments,=20 especially during the Second World War. During the Nuremberg War Crime = Trials,=20 the Nuremberg code was drafted as a set of standards for judging = physicians and=20 scientists who had conducted biomedical experiments on concentration = camp=20 prisoners. This code became the prototype of many later codes(= 1)=20 intended to assure that research involving human subjects would be = carried out=20 in an ethical manner.=20

The codes consist of rules, some general, others specific, that guide = the=20 investigators or the reviewers of research in their work. Such rules = often are=20 inadequate to cover complex situations; at times they come into = conflict, and=20 they are frequently difficult to interpret or apply. Broader ethical = principles=20 will provide a basis on which specific rules may be formulated, = criticized and=20 interpreted.=20

Three principles, or general prescriptive judgments, that are = relevant to=20 research involving human subjects are identified in this statement. = Other=20 principles may also be relevant. These three are comprehensive, however, = and are=20 stated at a level of generalization that should assist scientists, = subjects,=20 reviewers and interested citizens to understand the ethical issues = inherent in=20 research involving human subjects. These principles cannot always be = applied so=20 as to resolve beyond dispute particular ethical problems. The objective = is to=20 provide an analytical framework that will guide the resolution of = ethical=20 problems arising from research involving human subjects.=20

This statement consists of a distinction between research and = practice, a=20 discussion of the three basic ethical principles, and remarks about the=20 application of these principles.

[= RETURN TO=20 TABLE OF CONTENTS]=20

Part A: Boundaries Between Practice &=20 Research

A. Boundaries Between Practice and Research=20

It is important to distinguish between biomedical and behavioral = research, on=20 the one hand, and the practice of accepted therapy on the other, in = order to=20 know what activities ought to undergo review for the protection of human = subjects of research. The distinction between research and practice is = blurred=20 partly because both often occur together (as in research designed to = evaluate a=20 therapy) and partly because notable departures from standard practice = are often=20 called "experimental" when the terms "experimental" and "research" are = not=20 carefully defined.=20

For the most part, the term "practice" refers to interventions that = are=20 designed solely to enhance the well-being of an individual patient or = client and=20 that have a reasonable expectation of success. The purpose of medical or = behavioral practice is to provide diagnosis, preventive treatment or = therapy to=20 particular individuals.(= 2)=20 By contrast, the term "research' designates an activity designed to test = an=20 hypothesis, permit conclusions to be drawn, and thereby to develop or = contribute=20 to generalizable knowledge (expressed, for example, in theories, = principles, and=20 statements of relationships). Research is usually described in a formal = protocol=20 that sets forth an objective and a set of procedures designed to reach = that=20 objective.=20

When a clinician departs in a significant way from standard or = accepted=20 practice, the innovation does not, in and of itself, constitute = research. The=20 fact that a procedure is "experimental," in the sense of new, untested = or=20 different, does not automatically place it in the category of research.=20 Radically new procedures of this description should, however, be made = the object=20 of formal research at an early stage in order to determine whether they = are safe=20 and effective. Thus, it is the responsibility of medical practice = committees,=20 for example, to insist that a major innovation be incorporated into a = formal=20 research project.(= 3)=20

Research and practice may be carried on together when research is = designed to=20 evaluate the safety and efficacy of a therapy. This need not cause any = confusion=20 regarding whether or not the activity requires review; the general rule = is that=20 if there is any element of research in an activity, that activity should = undergo=20 review for the protection of human subjects.

Part B: Basic Ethical = Principles

B. Basic Ethical Principles=20

The expression "basic ethical principles" refers to those general = judgments=20 that serve as a basic justification for the many particular ethical=20 prescriptions and evaluations of human actions. Three basic principles, = among=20 those generally accepted in our cultural tradition, are particularly = relevant to=20 the ethics of research involving human subjects: the principles of = respect of=20 persons, beneficence and justice.=20

1. Respect for Persons. -- Respect for = persons=20 incorporates at least two ethical convictions: first, that individuals = should be=20 treated as autonomous agents, and second, that persons with diminished = autonomy=20 are entitled to protection. The principle of respect for persons thus = divides=20 into two separate moral requirements: the requirement to acknowledge = autonomy=20 and the requirement to protect those with diminished autonomy.=20

An autonomous person is an individual capable of deliberation about = personal=20 goals and of acting under the direction of such deliberation. To respect = autonomy is to give weight to autonomous persons' considered opinions = and=20 choices while refraining from obstructing their actions unless they are = clearly=20 detrimental to others. To show lack of respect for an autonomous agent = is to=20 repudiate that person's considered judgments, to deny an individual the = freedom=20 to act on those considered judgments, or to withhold information = necessary to=20 make a considered judgment, when there are no compelling reasons to do = so.=20

However, not every human being is capable of self-determination. The = capacity=20 for self-determination matures during an individual's life, and some = individuals=20 lose this capacity wholly or in part because of illness, mental = disability, or=20 circumstances that severely restrict liberty. Respect for the immature = and the=20 incapacitated may require protecting them as they mature or while they = are=20 incapacitated.=20

Some persons are in need of extensive protection, even to the point = of=20 excluding them from activities which may harm them; other persons = require little=20 protection beyond making sure they undertake activities freely and with=20 awareness of possible adverse consequence. The extent of protection = afforded=20 should depend upon the risk of harm and the likelihood of benefit. The = judgment=20 that any individual lacks autonomy should be periodically reevaluated = and will=20 vary in different situations.=20

In most cases of research involving human subjects, respect for = persons=20 demands that subjects enter into the research voluntarily and with = adequate=20 information. In some situations, however, application of the principle = is not=20 obvious. The involvement of prisoners as subjects of research provides = an=20 instructive example. On the one hand, it would seem that the principle = of=20 respect for persons requires that prisoners not be deprived of the = opportunity=20 to volunteer for research. On the other hand, under prison conditions = they may=20 be subtly coerced or unduly influenced to engage in research activities = for=20 which they would not otherwise volunteer. Respect for persons would then = dictate=20 that prisoners be protected. Whether to allow prisoners to "volunteer" = or to=20 "protect" them presents a dilemma. Respecting persons, in most hard = cases, is=20 often a matter of balancing competing claims urged by the principle of = respect=20 itself.=20

2. Beneficence. -- Persons are treated = in an=20 ethical manner not only by respecting their decisions and protecting = them from=20 harm, but also by making efforts to secure their well-being. Such = treatment=20 falls under the principle of beneficence. The term "beneficence" is = often=20 understood to cover acts of kindness or charity that go beyond strict=20 obligation. In this document, beneficence is understood in a stronger = sense, as=20 an obligation. Two general rules have been formulated as complementary=20 expressions of beneficent actions in this sense: (1) do not harm = and=20 (2) maximize possible benefits and minimize possible harms.=20

The Hippocratic maxim "do no harm" has long been a fundamental = principle of=20 medical ethics. Claude Bernard extended it to the realm of research, = saying that=20 one should not injure one person regardless of the benefits that might = come to=20 others. However, even avoiding harm requires learning what is harmful; = and, in=20 the process of obtaining this information, persons may be exposed to = risk of=20 harm. Further, the Hippocratic Oath requires physicians to benefit their = patients "according to their best judgment." Learning what will in fact = benefit=20 may require exposing persons to risk. The problem posed by these = imperatives is=20 to decide when it is justifiable to seek certain benefits despite the = risks=20 involved, and when the benefits should be foregone because of the risks. =

The obligations of beneficence affect both individual investigators = and=20 society at large, because they extend both to particular research = projects and=20 to the entire enterprise of research. In the case of particular = projects,=20 investigators and members of their institutions are obliged to give = forethought=20 to the maximization of benefits and the reduction of risk that might = occur from=20 the research investigation. In the case of scientific research in = general,=20 members of the larger society are obliged to recognize the longer term = benefits=20 and risks that may result from the improvement of knowledge and from the = development of novel medical, psychotherapeutic, and social procedures.=20

The principle of beneficence often occupies a well-defined justifying = role in=20 many areas of research involving human subjects. An example is found in = research=20 involving children. Effective ways of treating childhood diseases and = fostering=20 healthy development are benefits that serve to justify research = involving=20 children -- even when individual research subjects are not direct = beneficiaries.=20 Research also makes it possible to avoid the harm that may result from = the=20 application of previously accepted routine practices that on closer=20 investigation turn out to be dangerous. But the role of the principle of = beneficence is not always so unambiguous. A difficult ethical problem = remains,=20 for example, about research that presents more than minimal risk without = immediate prospect of direct benefit to the children involved. Some have = argued=20 that such research is inadmissible, while others have pointed out that = this=20 limit would rule out much research promising great benefit to children = in the=20 future. Here again, as with all hard cases, the different claims covered = by the=20 principle of beneficence may come into conflict and force difficult = choices.=20

3. Justice. -- Who ought to receive the = benefits of=20 research and bear its burdens? This is a question of justice, in the = sense of=20 "fairness in distribution" or "what is deserved." An injustice occurs = when some=20 benefit to which a person is entitled is denied without good reason or = when some=20 burden is imposed unduly. Another way of conceiving the principle of = justice is=20 that equals ought to be treated equally. However, this statement = requires=20 explication. Who is equal and who is unequal? What considerations = justify=20 departure from equal distribution? Almost all commentators allow that=20 distinctions based on experience, age, deprivation, competence, merit = and=20 position do sometimes constitute criteria justifying differential = treatment for=20 certain purposes. It is necessary, then, to explain in what respects = people=20 should be treated equally. There are several widely accepted = formulations of=20 just ways to distribute burdens and benefits. Each formulation mentions = some=20 relevant property on the basis of which burdens and benefits should be=20 distributed. These formulations are (1) to each person an equal = share,=20 (2) to each person according to individual need, (3) to = each=20 person according to individual effort, (4) to each person = according to=20 societal contribution, and (5) to each person according to merit. =

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

Against this historical background, it can be seen how conceptions of = justice=20 are relevant to research involving human subjects. For example, the = selection of=20 research subjects needs to be scrutinized in order to determine whether = some=20 classes (e.g., welfare patients, particular racial and ethnic = minorities, or=20 persons confined to institutions) are being systematically selected = simply=20 because of their easy availability, their compromised position, or their = manipulability, rather than for reasons directly related to the problem = being=20 studied. Finally, whenever research supported by public funds leads to = the=20 development of therapeutic devices and procedures, justice demands both = that=20 these not provide advantages only to those who can afford them and that = such=20 research should not unduly involve persons from groups unlikely to be = among the=20 beneficiaries of subsequent applications of the research.

Part C: Applications

C. Applications=20

Applications of the general principles to the conduct of research = leads to=20 consideration of the following requirements: informed consent, = risk/benefit=20 assessment, and the selection of subjects of research.=20

1. Informed Consent. -- Respect for = persons=20 requires that subjects, to the degree that they are capable, be given = the=20 opportunity to choose what shall or shall not happen to them. This = opportunity=20 is provided when adequate standards for informed consent are satisfied.=20

While the importance of informed consent is unquestioned, controversy = prevails over the nature and possibility of an informed consent. = Nonetheless,=20 there is widespread agreement that the consent process can be analyzed = as=20 containing three elements: information, comprehension and voluntariness. =

Information. Most codes of research establish specific items = for=20 disclosure intended to assure that subjects are given sufficient = information.=20 These items generally include: the research procedure, their purposes, = risks and=20 anticipated benefits, alternative procedures (where therapy is = involved), and a=20 statement offering the subject the opportunity to ask questions and to = withdraw=20 at any time from the research. Additional items have been proposed, = including=20 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=20 standard should be for judging how much and what sort of information = should be=20 provided. One standard frequently invoked in medical practice, namely = the=20 information commonly provided by practitioners in the field or in the = locale, is=20 inadequate since research takes place precisely when a common = understanding does=20 not exist. Another standard, currently popular in malpractice law, = requires the=20 practitioner to reveal the information that reasonable persons would = wish to=20 know in order to make a decision regarding their care. This, too, seems=20 insufficient since the research subject, being in essence a volunteer, = may wish=20 to know considerably more about risks gratuitously undertaken than do = patients=20 who deliver themselves into the hand of a clinician for needed care. It = may be=20 that a standard of "the reasonable volunteer" should be proposed: the = extent and=20 nature of information should be such that persons, knowing that the = procedure is=20 neither necessary for their care nor perhaps fully understood, can = decide=20 whether they wish to participate in the furthering of knowledge. Even = when some=20 direct benefit to them is anticipated, the subjects should understand = clearly=20 the range of risk and the voluntary nature of participation.=20

A special problem of consent arises where informing subjects of some=20 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=20 being invited to participate in research of which some features will not = be=20 revealed until the research is concluded. In all cases of research = involving=20 incomplete disclosure, such research is justified only if it is clear = that=20 (1) incomplete disclosure is truly necessary to accomplish the = goals of=20 the research, (2) there are no undisclosed risks to subjects that = are=20 more than minimal, and (3) there is an adequate plan for = debriefing=20 subjects, when appropriate, and for dissemination of research results to = them.=20 Information about risks should never be withheld for the purpose of = eliciting=20 the cooperation of subjects, and truthful answers should always be given = to=20 direct questions about the research. Care should be taken to distinguish = cases=20 in which disclosure would destroy or invalidate the research from cases = in which=20 disclosure would simply inconvenience the investigator.=20

Comprehension. The manner and context in which information is = conveyed=20 is as important as the information itself. For example, presenting = information=20 in a disorganized and rapid fashion, allowing too little time for = consideration=20 or curtailing opportunities for questioning, all may adversely affect a=20 subject's ability to make an informed choice.=20

Because the subject's ability to understand is a function of = intelligence,=20 rationality, maturity and language, it is necessary to adapt the = presentation of=20 the information to the subject's capacities. Investigators are = responsible for=20 ascertaining that the subject has comprehended the information. While = there is=20 always an obligation to ascertain that the information about risk to = subjects is=20 complete and adequately comprehended, when the risks are more serious, = that=20 obligation increases. On occasion, it may be suitable to give some oral = or=20 written tests of comprehension.=20

Special provision may need to be made when comprehension is severely = limited=20 -- for example, by conditions of immaturity or mental disability. Each = class of=20 subjects that one might consider as incompetent (e.g., infants and young = children, mentally disable patients, the terminally ill and the = comatose) should=20 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,=20 whether or not to participate in research. The objections of these = subjects to=20 involvement should be honored, unless the research entails providing = them a=20 therapy unavailable elsewhere. Respect for persons also requires seeking = the=20 permission of other parties in order to protect the subjects from harm. = Such=20 persons are thus respected both by acknowledging their own wishes and by = the use=20 of third parties to protect them from harm.=20

The third parties chosen should be those who are most likely to = understand=20 the incompetent subject's situation and to act in that person's best = interest.=20 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=20 withdraw the subject from the research, if such action appears in the = subject's=20 best interest.=20

Voluntariness. An agreement to participate in research = constitutes a=20 valid consent only if voluntarily given. This element of informed = consent=20 requires conditions free of coercion and undue influence. Coercion = occurs when=20 an overt threat of harm is intentionally presented by one person to = another in=20 order to obtain compliance. Undue influence, by contrast, occurs through = an=20 offer of an excessive, unwarranted, inappropriate or improper reward or = other=20 overture in order to obtain compliance. Also, inducements that would = ordinarily=20 be acceptable may become undue influences if the subject is especially=20 vulnerable.=20

Unjustifiable pressures usually occur when persons in positions of = authority=20 or commanding influence -- especially where possible sanctions are = involved --=20 urge a course of action for a subject. A continuum of such influencing = factors=20 exists, however, and it is impossible to state precisely where = justifiable=20 persuasion ends and undue influence begins. But undue influence would = include=20 actions such as manipulating a person's choice through the controlling = influence=20 of a close relative and threatening to withdraw health services to which = an=20 individual would otherwise be entitle.=20

2. Assessment of Risks and Benefits. -- = The=20 assessment of risks and benefits requires a careful arrayal of relevant = data,=20 including, in some cases, alternative ways of obtaining the benefits = sought in=20 the research. Thus, the assessment presents both an opportunity and a=20 responsibility to gather systematic and comprehensive information about = proposed=20 research. For the investigator, it is a means to examine whether the = proposed=20 research is properly designed. For a review committee, it is a method = for=20 determining whether the risks that will be presented to subjects are = justified.=20 For prospective subjects, the assessment will assist the determination = whether=20 or not to participate.=20

The Nature and Scope of Risks and Benefits. The requirement = that=20 research be justified on the basis of a favorable risk/benefit = assessment bears=20 a close relation to the principle of beneficence, just as the moral = requirement=20 that informed consent be obtained is derived primarily from the = principle of=20 respect for persons. The term "risk" refers to a possibility that harm = may=20 occur. However, when expressions such as "small risk" or "high risk" are = used,=20 they usually refer (often ambiguously) both to the chance (probability) = of=20 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=20 positive value related to health or welfare. Unlike, "risk," "benefit" = is not a=20 term that expresses probabilities. Risk is properly contrasted to = probability of=20 benefits, and benefits are properly contrasted with harms rather than = risks of=20 harm. Accordingly, so-called risk/benefit assessments are concerned with = the=20 probabilities and magnitudes of possible harm and anticipated benefits. = Many=20 kinds of possible harms and benefits need to be taken into account. = There are,=20 for example, risks of psychological harm, physical harm, legal harm, = social harm=20 and economic harm and the corresponding benefits. While the most likely = types of=20 harms to research subjects are those of psychological or physical pain = or=20 injury, other possible kinds should not be overlooked.=20

Risks and benefits of research may affect the individual subjects, = the=20 families of the individual subjects, and society at large (or special = groups of=20 subjects in society). Previous codes and Federal regulations have = required that=20 risks to subjects be outweighed by the sum of both the anticipated = benefit to=20 the subject, if any, and the anticipated benefit to society in the form = of=20 knowledge to be gained from the research. In balancing these different = elements,=20 the risks and benefits affecting the immediate research subject will = normally=20 carry special weight. On the other hand, interests other than those of = the=20 subject may on some occasions be sufficient by themselves to justify the = risks=20 involved in the research, so long as the subjects' rights have been = protected.=20 Beneficence thus requires that we protect against risk of harm to = subjects and=20 also that we be concerned about the loss of the substantial benefits = that might=20 be gained from research.=20

The Systematic Assessment of Risks and Benefits. It is = commonly said=20 that benefits and risks must be "balanced" and shown to be "in a = favorable=20 ratio." The metaphorical character of these terms draws attention to the = difficulty of making precise judgments. Only on rare occasions will = quantitative=20 techniques be available for the scrutiny of research protocols. However, = the=20 idea of systematic, nonarbitrary analysis of risks and benefits should = be=20 emulated insofar as possible. This ideal requires those making decisions = about=20 the justifiability of research to be thorough in the accumulation and = assessment=20 of information about all aspects of the research, and to consider = alternatives=20 systematically. This procedure renders the assessment of research more = rigorous=20 and precise, while making communication between review board members and = investigators less subject to misinterpretation, misinformation and = conflicting=20 judgments. Thus, there should first be a determination of the validity = of the=20 presuppositions of the research; then the nature, probability and = magnitude of=20 risk should be distinguished with as much clarity as possible. The = method of=20 ascertaining risks should be explicit, especially where there is no = alternative=20 to the use of such vague categories as small or slight risk. It should = also be=20 determined whether an investigator's estimates of the probability of = harm or=20 benefits are reasonable, as judged by known facts or other available = studies.=20

Finally, assessment of the justifiability of research should reflect = at least=20 the following considerations: (i) Brutal or inhumane treatment of = human=20 subjects is never morally justified. (ii) Risks should be reduced = to=20 those necessary to achieve the research objective. It should be = determined=20 whether it is in fact necessary to use human subjects at all. Risk can = perhaps=20 never be entirely eliminated, but it can often be reduced by careful = attention=20 to alternative procedures. (iii) When research involves = significant risk=20 of serious impairment, review committees should be extraordinarily = insistent on=20 the justification of the risk (looking usually to the likelihood of = benefit to=20 the subject -- or, in some rare cases, to the manifest voluntariness of = the=20 participation). (iv) When vulnerable populations are involved in=20 research, the appropriateness of involving them should itself be = demonstrated. A=20 number of variables go into such judgments, including the nature and = degree of=20 risk, the condition of the particular population involved, and the = nature and=20 level of the anticipated benefits. (v) Relevant risks and = benefits must=20 be thoroughly arrayed in documents and procedures used in the informed = consent=20 process.=20

3. Selection of Subjects. -- Just as the = principle=20 of respect for persons finds expression in the requirements for consent, = and the=20 principle of beneficence in risk/benefit assessment, the principle of = justice=20 gives rise to moral requirements that there be fair procedures and = outcomes in=20 the selection of research subjects.=20

Justice is relevant to the selection of subjects of research at two = levels:=20 the social and the individual. Individual justice in the selection of = subjects=20 would require that researchers exhibit fairness: thus, they should not = offer=20 potentially beneficial research only to some patients who are in their = favor or=20 select only "undesirable" persons for risky research. Social justice = requires=20 that distinction be drawn between classes of subjects that ought, and = ought not,=20 to participate in any particular kind of research, based on the ability = of=20 members of that class to bear burdens and on the appropriateness of = placing=20 further burdens on already burdened persons. Thus, it can be considered = a matter=20 of social justice that there is an order of preference in the selection = of=20 classes of subjects (e.g., adults before children) and that some classes = of=20 potential subjects (e.g., the institutionalized mentally infirm or = prisoners)=20 may be involved as research subjects, if at all, only on certain = conditions.=20

Injustice may appear in the selection of subjects, even if individual = subjects are selected fairly by investigators and treated fairly in the = course=20 of research. Thus injustice arises from social, racial, sexual and = cultural=20 biases institutionalized in society. Thus, even if individual = researchers are=20 treating their research subjects fairly, and even if IRBs are taking = care to=20 assure that subjects are selected fairly within a particular = institution, unjust=20 social patterns may nevertheless appear in the overall distribution of = the=20 burdens and benefits of research. Although individual institutions or=20 investigators may not be able to resolve a problem that is pervasive in = their=20 social setting, they can consider distributive justice in selecting = research=20 subjects.=20

Some populations, especially institutionalized ones, are already = burdened in=20 many ways by their infirmities and environments. When research is = proposed that=20 involves risks and does not include a therapeutic component, other less = burdened=20 classes of persons should be called upon first to accept these risks of=20 research, except where the research is directly related to the specific=20 conditions of the class involved. Also, even though public funds for = research=20 may often flow in the same directions as public funds for health care, = it seems=20 unfair that populations dependent on public health care constitute a = pool of=20 preferred research subjects if more advantaged populations are likely to = be the=20 recipients of the benefits.=20

One special instance of injustice results from the involvement of = vulnerable=20 subjects. Certain groups, such as racial minorities, the economically=20 disadvantaged, the very sick, and the institutionalized may continually = be=20 sought as research subjects, owing to their ready availability in = settings where=20 research is conducted. Given their dependent status and their frequently = compromised capacity for free consent, they should be protected against = the=20 danger of being involved in research solely for administrative = convenience, or=20 because they are easy to manipulate as a result of their illness or=20 socioeconomic condition.

(1)=20 Since 1945, various codes for the proper and responsible conduct of = human=20 experimentation in medical research have been adopted by different=20 organizations. The best known of these codes are the Nuremberg Code of = 1947, the=20 Helsinki Declaration of 1964 (revised in 1975), and the 1971 Guidelines=20 (codified into Federal Regulations in 1974) issued by the U.S. = Department of=20 Health, Education, and Welfare Codes for the conduct of social and = behavioral=20 research have also been adopted, the best known being that of the = American=20 Psychological Association, published in 1973.=20

(2)=20 Although practice usually involves interventions designed solely to = enhance the=20 well-being of a particular individual, interventions are sometimes = applied to=20 one individual for the enhancement of the well-being of another (e.g., = blood=20 donation, skin grafts, organ transplants) or an intervention may have = the dual=20 purpose of enhancing the well-being of a particular individual, and, at = the same=20 time, providing some benefit to others (e.g., vaccination, which = protects both=20 the person who is vaccinated and society generally). The fact that some = forms of=20 practice have elements other than immediate benefit to the individual = receiving=20 an intervention, however, should not confuse the general distinction = between=20 research and practice. Even when a procedure applied in practice may = benefit=20 some other person, it remains an intervention designed to enhance the = well-being=20 of a particular individual or groups of individuals; thus, it is = practice and=20 need not be reviewed as research.=20

(3)=20 Because the problems related to social experimentation may differ = substantially=20 from those of biomedical and behavioral research, the Commission = specifically=20 declines to make any policy determination regarding such research at = this time.=20 Rather, the Commission believes that the problem ought to be addressed = by one of=20 its successor bodies.