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Full text of "The Belmont report : ethical principles and guidelines for the protection of human subjects of research"

The 

Belmont 

Report 

Ethical Principles 

and Guidelines for 

the Protection of 

Human Subjects 

of Research 



The National Commission 

for the Protection of Human Subjects 

of Biomedical and Behavioral 

Research 



The 

Belmont 

Report 

Ethical Principles 

and Guidelines for 

the Protection of 

Human Subjects 

of Research 



The National Commission 

for the Protection of Human Subjects 

of Biomedical and Behavioral 

Research 



DHEW Publication No. (OS) 78-0012 



For sale by tho Superintendent of Documents, U.S. Government Printing Office, Washington, D.C. 20402 



1 n% 



a^VHBW nu» 



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

Westwood Building, Room 125 

5333 Westbard Avenue 

= Bethesda, Man/land 20016 
September 30, 1978 

The President 
The White House 
Washington, D.C. 20500 

Dear Mr. President: 

On behalf of the National Commission for the Protection of Human 
Subjects of Biomedical and Behavioral Research, I am pleased to trans- 
mit our "Belmont Report: Ethical Principles and Guidelines for the 
Protection of Human Subjects of Research. " The identification of basic 
ethical principles that should underlie the conduct of research involving 
human subjects, and the development of guidelines to assure that such 
principles are followed, were topics of studies set forth in the Com- 
mission's mandate under Public Law 93-348. This mandate also 
directs the Commission to submit its report to the President, the 
Congress, and the Secretary of Health, Education, and Welfare. 

Unlike most of the previous reports of the Commission, the 
Belmont Report does not make specific recommendations for admin- 
istrative actions by the Secretary of Health, Education, and Welfare. 
Instead, it is our recommendation that the Belmont Report be adopted 
in its entirety as a statement of departmental policy on the conduct of 
research involving human subjects. Publication and dissemination of 
this policy will provide federal employees, members of Institutional 
Review Boards and scientific investigators with common points of 
reference for the analysis of ethical issues in human experimentation. 
While the principles cannot always be applied so as to resolve beyond 
dispute particular ethical problems, they provide an analytical frame- 
work that will guide the resolution of ethical problems arising from 
research involving human subjects. 

The Belmont Report is the outgrowth of an intensive four-day period 
of discussions that were held in February 1976 at the Smithsonian Insti- 
tution's Belmont Conference Center and the monthly Commission's 
deliberations that have been conducted over the nearly four years of 
our existence. 

We appreciate the opportunity to have worked on this fundamental 
task in the protection of human research subjects. 



tfully, 




X 




lenneth J.rfcyan, M. D. 
Chairman 



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

Westwood Building, Room 125 

5333 Westbard Avenue 

■ Bethesda, Maryland 20016 
September 30, 1978 

The Honorable Walter F. Mondale 
President of the United States Senate 
Washington, D.C. 20510 

Dear Mr. President: 

On behalf of the National Commission for the Protection of Human 
Subjects of Biomedical and Behavioral Research, I am pleased to trans- 
mit our "Belmont Report: Ethical Principles and Guidelines for the 
Protection of Human Subjects of Research. " The identification of basic 
ethical principles that should underlie the conduct of research involving 
human subjects, and the development of guidelines to assure that such 
principles are followed, were topics of studies set forth in the Com- 
mission's mandate under Public Law 93-348. This mandate also 
directs the Commission to submit its report to the President, the 
Congress, and the Secretary of Health, Education, and Welfare. 

Unlike most of the previous reports of the Commission, the 
Belmont Report does not make specific recommendations for admin- 
istrative actions by the Secretary of Health, Education, and Welfare. 
Instead, it is our recommendation that the Belmont Report be adopted 
in its entirety as a statement of departmental policy on the conduct of 
research involving human subjects. Publication and dissemination of 
this policy will provide federal employees, members of Institutional 
Review Boards and scientific investigators with common points of 
reference for the analysis of ethical issues in human experimentation. 
While the principles cannot always be applied so as to resolve beyond 
dispute particular ethical problems, they provide an analytical frame- 
work that will guide the resolution of ethical problems arising from 
research involving human subjects. 

The Belmont Report is the outgrowth of an intensive four-day period 
of discussions that were held in February 1976 at the Smithsonian Insti- 
tution's Belmont Conference Center and the monthly Commission's 
deliberations that have been conducted over the nearly four years of 
our existence. 

We appreciate the opportunity to have worked on this fundamental 
task in the protection of human research subjects. 



Respectfully, 




lenneth J. feyan, M.D. 
Chairman 



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



= 3er e<c z * c -» crc 2CO 6 



he ~ o n c ■"* = '■* " — _ " — ~i = s ? "* • e ill I r , 
Speaker of fee House c: Representatives 
Washington* D.C. 20515 

C ear Mr. Speaker: 

Do behalf cf fee I'acicral C tissioa fcr Hie ?rc:e::icr :: Hmnan 

mil cur 3 elm cut Report: Ethical Principles and 3-uiielir.es ::r the 

rrircirles are followed, were topics :: srccies set forth ir Hie i cm- 
directs ice Cc:rmissicr to submit its report to "ie Presiierc, ire 
Congress, and ice Secretary :: Healir, Education, ani "Welfare. 

Unlike most o: ice previous repcrcs :: the C r : i s s 1 1 r , ice 

Belmont Herorc ices rcc make sceciiic c s ~ . end ati cans fcr = i — ~- 

istrative actions by ice Secretary c: Healer, Zoucacicr, ari Welfare. 
Instead, it is our re corrmer ration icac tie B elm err: Report 'ce licccei 
ir its entirety as a statement c: ieparcmertal policy cr ice conduct c: 

iris policy *~11 provide federal exnployeeSj members c: mstltutional 

Review Boards arc sciercific investigators with cemmor pcircs c: 

While ice prirciples ccmcc always ce cppliei sc as :c resolve beyond 

dispute particuicr eicioal problems j theyprovide an analytical frame- 
work icac -vill guide ere resclucicr of ethical problems arising from 

research involving reman subjects. 

Tie Belmont P.epcrc is ire outgrowth of an intensive four-day pence 
of discussions that were held in February 19T5 ac ice Smichsonian Irsti- 
rurier s Belmor": Com'erence Center and ice monthly Commission s 
deliberations icac rave been conducted ever ice nearly four years of 

our existence, 

We appreciate ice opportunity :o rave --crkei cr ices fundamental 
task in the protection of human research subjects. 



P.fsreccfullv, 




1 



SK 



Kenneth J. RyttJ M. E . 

Chairman 



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

Westwood Building, Room 125 
5333 Westbard Avenue 

— Bethesda, Maryland 20016 

September 30, 1978 

Honorable Joseph A. Califano, Jr. 
Secretary of Health, Education, and Welfare 
Washington, D.C. 20201 

Dear Mr. Secretary: 

On behalf of the National Commission for the Protection of Human 
Subjects of Biomedical and Behavioral Research, I am pleased to trans- 
mit our "Belmont Report: Ethical Principles and Guidelines for the 
Protection of Human Subjects of Research. " The identification of basic 
ethical principles that should underlie the conduct of research involving 
human subjects, and the development of guidelines to assure that such 
principles are followed, were topics of studies set forth in the Com- 
mission's mandate under Public Law 93-348. This mandate also 
directs the Commission to submit its report to the President, the 
Congress, and the Secretary of Health, Education, and Welfare. 

Unlike most of the previous reports of the Commission, the 
Belmont Report does not make specific recommendations for admin- 
istrative actions by the Secretary of Health, Education, and Welfare. 
Instead, it is our recommendation that the Belmont Report be adopted 
in its entirety as a statement of departmental policy on the conduct of 
research involving human subjects. Publication and dissemination of 
this policy will provide federal employees, members of Institutional 
Review Boards and scientific investigators with common points of 
reference for the analysis of ethical issues in human experimentation. 
While the principles cannot always be applied so as to resolve beyond 
dispute particular ethical problems, they provide an analytical frame- 
work that will guide the resolution of ethical problems arising from 
research involving human subjects. 

The Belmont Report is the outgrowth of an intensive four-day period 
of discussions that were held in February 1976 at the Smithsonian Insti- 
tution's Belmont Conference Center and the monthly Commission's 
deliberations that have been conducted over the nearly four years of 
our existence. 

We appreciate the opportunity to have worked on this fundamental 
task in the protection of human research subjects. 

Respectfully, 



Kenneth J. Ryan, M. D. 
Chairman 



NATIONAL COMMISSION FOR THE PROTECTION OF HUMAN SUBJECTS 
OF BIOMEDICAL AND BEHAVIORAL RESEARCH 



MEMBERS OF THE COMMISSION 



Kenneth John Ryan, M.D., Chairman 

Chief of Staff 
Boston Hospital for Women 



Joseph V. Brady, Ph.D. 

Professor of Behavioral Biology 
Johns Hopkins University 



Karen Lebacqz, Ph.D. 

Associate Professor of Christian Ethics 
Pacific School of Religion 



Robert E. Cooke, M.D. 

President 

Medical College of Pennsylvania 



David W. Louisell, J.D. 

Professor of Law 

University of California at Berkeley 



Dorothy I. Height 

President 

National Council of Negro Women, Inc. 



Donald W. Seldin, M.D. 

Professor and Chairman 
Department of Internal Medicine 
University of Texas at Dallas 



Albert R. Jonsen, Ph.D. 

Associate Professor of Bioethics 
University of California at San Francisco 



Eliot Stellar, Ph.D. 

Provost of the University and 
Professor of Physiological Psychology 
University of Pennsylvania 



Patricia King, J.D. 

Associate Professor of Law 
Georgetown University Law Center 



Robert H. Turtle, LL.B. 

Attorney 

VomBaur, Coburn, Simmons & Turtle 

Washington, D.C. 



'Deceased 



NATIONAL COMMISSION FOR THE PROTECTION OF HUMAN SUBJECTS 
OF BIOMEDICAL AND BEHAVIORAL RESEARCH 



COMMISSION STAFF 



PROFESSIONAL STAFF 

Michael S. Yesley, J.D. 
Staff Director 

Barbara Mishkin, M.A. 
Assistant Staff Director 

Duane Alexander, M.D. 
Pediatrics 

Tom L. Beauchamp, Ph.D. 
Philosophy 

Bradford H. Gray, Ph.D. 
Sociology 

Miriam Kelty, Ph.D. 
Psychology 

Betsy Singer 

Public Information Officer 

Dorle Vawter 

Research Assistant 



SUPPORT STAFF 
Pamela L. Driscoll 
Marie D. Madigan 
Coral M. Nydegger 
Erma L. Pender 



SPECIAL CONSULTANTS 
Robert J. Levine, M.D. 
Stephen Toulmin, Ph.D. 



TABLE OF CONTENTS 

A. Boundaries Between Practice and Research 2 

B. Basic Ethical Principles 4 

1 . Respect for Persons 4 

2. Beneficence 6 

3. Justice 8 

C. Applications 10 

1. Informed Consent 10 

2. Assessment of Risks and Benefits 14 

3. Selection of Subjects 18 



BELMONT REPORT 



ETHICAL PRINCIPLES AND GUIDELINES FOR RESEARCH 
INVOLVING HUMAN SUBJECTS 



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 ex- 
periments, especially during the Second World War, During the Nuremberg 
War Crimes 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 for- 
mulated, criticized and interpreted. 

Three principles, or general prescriptive judgments, that are relevant 
to research involving human subjects are identified in this statement. 



* 



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

1 



Other principles may also be relevant. These three are comprehensive, how- 
ever, 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 ap- 
plication 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 de- 
signed 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 de- 
signed to test a hypothesis, permit conclusions to be drawn, and thereby to 
develop or contribute to general izable 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 



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



incorporated into a formal research project,* 

Research and practice may be carried on together when research is de- 
signed 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 judg- 
ments 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 basic ethical convictions 
first, that individuals should be treated as autonomous agents, and second, 
that persons with diminished autonomy are entitled to protection, The 



* 



Because the problems related to social experimentation may differ substan- 
tially from those of biomedical and behavioral research, the Commission 
specifically declines to make any policy determination regarding such re- 
search at this time. Rather, the Commission believes that the problem 
ought to be addressed by one of its successor bodies. 



principle of respect for persons thus divides into two separate moral re- 
quirements: 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 a lack of respect for an autonomous 
agent is to repudiate that person's considered judgments , to deny an indi- 
vidual the freedom to act on those considered judgments, or to withhold infor- 
mation 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. Res- 
pect 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 judg- 
ment 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 oppor- 
tunity to volunteer for research. On the other hand, under prison conditions 
they may be subtly coerced or unduly influenced to engage in research acti- 
vities 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 pos- 
sible harms, 



The Hippocratic maxim "do no harm" has long been a fundamental princi- 
ple 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 cer- 
tain 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 pro- 
jects 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 the 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 diffi- 
cult ethical problem remains, for example, about research that presents more 
than minimal risk withhout immediate prospect of direct benefit to the child- 
ren 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 per- 
son 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 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 



8 



equally, There are several widely accepted formulations of just ways to dis- 
tribute burdens and benefits, Each formulation mentions some relevant proper- 
ty 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 ac- 
cording to individual need, (3) to each person according to individual ef- 
fort, (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 condemmed as 
a particularly flagrant injustice. In this country, in the 1940s, the Tuske- 
gee 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 deter- 
mine whether some classes (e.g,, welfare patients, particular racial and 



ethnic minorities, or persons confined to institutions) are being syste- 
matically selected simply because of their easy availability, their compro- 
mised 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 

Application of the general principles to the conduct of research leads 
to consideration of the following requirements: informed consent, risk/bene- 
fit 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 con- 
taining three elements: information, comprehension and voluntariness. 



10 



Information , Most codes of research establish specific items for dis- 
closure 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 respon- 
sible 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 informa- 
tion should be provided. One standard frequently invoked in medical prac- 
tice, 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 regard- 
ing 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 
hands of a clinician for needed care, It may be that a standard of "the 
reasonable volunteer" should be proposed: the extent and nature of infor- 
mation 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. 

11 



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 sub- 
jects, 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 informa- 
tion in a disorganized and rapid fashion, allowing too little time for con- 
sideration 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 intelli- 
gence, rationality, maturity and language, it is necessary to adapt the pres- 
entation of the information to the subject's capacities, Investigators are 
responsible for ascertaining that the subject has comprehended the information, 



12 



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 test 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., in- 
fants 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. Res- 
pect for persons also requires seeking the permission of other parties 
in order to protect the subjects from harm. Such persons are thus res- 
pected 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 un- 
derstand 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 able to withdraw the subject from the research, if such action 
appears in the subject's best interest. 



13 



Voluntariness . An agreement to participate in research constitutes 
a valid consent only if voluntarily given. This element of informed con- 
sent 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, occures through an offer of an excessive, unwarranted, inappro- 
priate 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 threat- 
ening to withdraw health services to which an individual would otherwise 
be entitled. 

2. Assessment of Risks and B enefits 

The assessment of risks and benefits requires a careful arrayal of 
rel event 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 comprehen- 
sive information about proposed research. For the investigator, it is 



14 



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 sub- 
jects, the assessment will assist the determination whether or not to 
participate. 

The Nature and Scope of Risks and Benefits . The requirement that re- 
search 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 possi- 
bility 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 (magni- 
tude) of the envisioned harm. 

The term "benefit" is used in the research context to refer to some- 
thing 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 contras- 
ted 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 be taken into account. There are, for example, risks 
of psychological harm, physical harm, legal harm, social harm and econo- 
mic harm and the corresponding benefits. While the most likely types 



15 



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 the 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 oc- 
casions be sufficient by themselves to justify the risks involved in the 
research, so long 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 quan- 
titative techniques be available for the scrutiny of research protocols. 
However, the idea of systematic, nonarbitrary analysis of risks and bene- 
fits 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 



16 



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 presupposi- 
tions of the research; then the nature, probability and magnitude of 
risk should be distinguished with as much clarity as possible. The me- 
thod 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 re- 
duced 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 re- 
search 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 appro- 
priateness of involving them should itself be demonstrated. A number 



17 



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 on to some patients who are 
in their favor or select only "undesirable" persons for risky research. So- 
cial justice requires that a 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 appropri- 
ateness of placing further burdens on already burdened persons. Thus, it 
can be considered a matter of social justice that there is an order of prefer- 
ence in the selection of classes of subjects (e.g., adults before children) 
and that some classes of potential subjects (e.g,, the institutionalized men- 
tally infirm or prisoners) may be involved as research subjects, if at all, 
only on certain conditions. 



18 



Injustice may appear in the selection of subjects, even if individual 
subjects are selected fairly by investigators and treated fairly in the 
course of the research. This 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 IRBs 
are taking care to assure that subjects are selected fairly within a par- 
ticular 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 prob- 
lem that is pervasive in their social setting, they can consider distribu- 
tive justice in selecting research subjects. 

Some populations, especially institutionalized ones, are already bur- 
dened 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 ac- 
cept 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 



19 



may continually be sought as research subjects, owing to their ready 
availability in settings where research is conducted. Given their de- 
pendent status and their frequently compromised capacity for free con- 
sent, 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 con- 
dition. 



20 



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