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  Please read the following article:

Vaisman, A., Linder, N., Lundin, J., Orchanian-Cheff, A., Coulibaly, J. T., Ephraim, R. K. D., & Bogoch, I. I. (2020). Artificial intelligence, diagnostic imaging and neglected tropical diseases: Ethical implications. World Health Organization: Bulletin of the World Health Organization, 98(4), 288-289. http://dx.doi.org/10.2471/BLT.19.237560

Discuss some of the primary ethical challenges that biomedical researchers encounter in the face of emerging technology? How can the ethical principles and protocols of the Belmont Report address modern ethical concerns and issues in highly technical modern clinical environments? Ensure to provide either a real-life example or realistic scenario for your proof of concept.

Embed course material concepts, principles, and theories (which require supporting citations) in your initial response along with at least three scholarly, peer-reviewed journal articles.

288 Bull World Health Organ 2020;98:288–289 | doi: http://dx.doi.org/10.2471/BLT.19.237560

Perspectives

Artificial intelligence, defined as a sys-
tem capable of interpreting and learning
from data to produce a specific goal,1 has
made significant advances in the field of
neglected tropical diseases. Specifically,
artificial intelligence is increasingly
applied to the task of interpreting im-
ages of such diseases and generating
accurate and reliable diagnoses that may
ultimately inform management of these
conditions. Neglected tropical diseases
affect over a billion people globally and
are a significant source of morbidity and
mortality in low- and middle-income
countries.2 Artificial intelligence has
the potential to transform how such dis-
eases are diagnosed and may contribute
to enabling clinical and public health
delivery in low- and middle-income
countries. For example, artificial intel-
ligence applied to neglected tropical
disease diagnosis may help drive point-
of-care clinical decision-making, iden-
tify outbreaks before they spread and
help map these diseases to guide public
health surveillance and control efforts.
The latest research in this field demon-
strates that novel diagnostic tools, such
as mobile phone microscopes have rap-
idly improved diagnostic characteristics
and broadened the scope of pathogens
tested, and have excellent functionality
in neglected tropical disease-endemic
settings.3,4 Such devices are already being
field tested and implemented on a lim-
ited scale, for example in Côte d’Ivoire.5

However, careful consideration to
several ethical concerns arising from
artificial intelligence-driven diagno-
ses of neglected tropical diseases in
low-resource settings is critical for
maximizing the benefit of this technol-
ogy.6 Artificial intelligence applications
focused on image-based diagnoses is

still in its infancy and therefore, now
is an opportune time to ensure that
these applications develop within an
ethical framework. Here, we outline
important ethical challenges faced by
low- and middle-income countries that
may benefit from the implementation of
these technologies. Key issues discussed
include the interrelationships between
stakeholder engagement, consent, data
security, accessibility of technology,
adhering to current and evolving care
standards and deciding how to effec-
tively use resources. Addressing these is-
sues during the design phase of artificial
intelligence technology will facilitate its
timely implementation and maximize
public health benefit.

Most published studies focusing
on the development of artificial intel-
ligence tools for image-based diagnoses
are conducted in laboratories based in
high-income countries. Consequently,
the limited engagement of scientists
and clinicians from endemic regions
may restrict the utility, and eventually
scale, of these technologies in precisely
the countries that would benefit the
most. Therefore, several stakeholders
should be involved from the earliest
phases in the development of artificial
intelligence tools.7 These stakeholders
include data scientists and engineers
from both low- and middle-income
countries affected by neglected tropical
diseases and those from high-income
countries currently working in artificial
intelligence diagnostics. Pairing teams
of data scientists and engineers would
enable capacity building in low- and
middle-income countries where there
is currently limited infrastructure to
develop such diagnostic tools. Other
important stakeholders include clinical,

public health, governmental and citizen
representation from low- and middle-
income countries affected by these
diseases. Such groups are critical in the
identification of priority areas, shaping
research questions and implementing
the technology into routine health-care
use. Private industry and governmental
bodies should also be instrumental in
the scale-up, licensing and regulation of
new diagnostic tools, and their involve-
ment and support during concept devel-
opment may help streamline product
development.8

Addressing ethical issues surround-
ing informed consent, an issue closely
intertwined with data security, is vital
in the development of artificial intelli-
gence image-based diagnostic tools for
neglected tropical diseases. Diagnostic
tests inherently involve some form of
biologic sample collection from a pa-
tient and this procedure is frequently
connected to patient-identifying in-
formation. Although these diagnoses
may be performed at the point of care,9
the collected specimens and images
may be subsequently used to train and
improve machine-learning algorithms.
Individuals providing samples must
consent to their biologic sample, and
perhaps other personal data. Similarly,
individuals must be notified of which
personal information is being used
and stored, where it is being stored,
who has access to this data, how it is
being accessed and how this personal
information is being used or may be
used in the future.1,6 Given that much
of this diagnosis technology has been
developed in high-income countries
for use in low- and middle-income
countries, special attention is required.
Therefore, the informed consent process

Artificial intelligence, diagnostic imaging and neglected tropical
diseases: ethical implications
Alon Vaisman,a Nina Linder,b Johan Lundin,c Ani Orchanian-Cheff,d Jean T Coulibaly,e Richard KD Ephraimf &
Isaac I Bogocha

a Division Infectious Diseases, Toronto General Hospital, University of Toronto, 14EN 209, 200 Elizabeth Street, Toronto, Ontario M5G 2C4, Canada.
b Department of Women’s and Children’s Health, International Maternal and Child health, Uppsala University, Sweden
c Department of Global Public Health, Karolinska Institutet, Stockholm, Sweden
d Health Sciences Library, University Health Network, Toronto, Canada.
e Unité de Formation et de Recherche Biosciences, Université Félix Houphouët-Boigny, Abidjan, Côte d’Ivoire.
f Department of Medical Laboratory Sciences, University of Cape Coast, Cape Coast, Ghana.
Correspondence to Isaac I Bogoch (email: [email protected]).
(Submitted: 15 May 2019 – Revised version received: 16 December 2019 – Accepted: 17 December 2019 – Published online: 3 March 2020 )

289Bull World Health Organ 2020;98:288–289| doi: http://dx.doi.org/10.2471/BLT.19.237560

Perspectives
Artificial intelligence for the diagnosis of neglected tropical diseasesAlon Vaisman et al.

in low- and middle-income countries
must adhere to the highest standards
that are respectful and inclusive of cul-
ture, language, religion, gender, age and
socioeconomic status.10

Ethical concerns may also arise due
to the accessibility of artificial intelli-
gence technology for neglected tropical
disease diagnoses. Since this technology
can be transformative to communities
burdened by such diseases, its accessibil-
ity to all affected populations, including
to those in underserviced and remote
communities, must be insured. Early
and broad stakeholder engagement in
project development can ensure that
artificial intelligence diagnostics tools
tailored for low- and middle-income
countries will be accessible and barri-
ers, such as affordability and scale will
be considered in countries burdened
by these diseases. Examples of mitigat-
ing access issues include facilitating the
development and use of open-source
software in the early stages of product
development to help lower implementa-
tion costs and share information.11

We must also examine how these
technologies affect the standards of
care as both the technology developed
and local care standards will continue
to evolve. While artificial intelligence-
based diagnoses of neglected tropical
diseases may evolve into preferred
methods for diagnosis, further advances

in this field and others will inevitably
take place, and appropriate regulation
and oversight will be essential to ensure
that diagnostic tools continue to adhere
to local standards of care.12 Hence,
early and continuous involvement of
government, industry and health-care
teams is essential for the continuous
maintenance of diagnostic quality.
Furthermore, as these technologies con-
tinue to evolve, low- and middle-income
countries must not be left behind as
image-based artificial intelligence diag-
nostic tools improve and expand in the
health-care sector.

Lastly, there may be unintended
consequences for implementing these
diagnostic tools in low- and middle-in-
come countries. While most intentions
seem to be laudable, such as facilitating
care in low-resource settings, many of
these countries have significant limita-
tions in health-care infrastructure and
challenges in the provision of health care
to large segments of their population.
The implementation of artificial intelli-
gence diagnostics could unintentionally
draw vital resources from other pro-
grammes. Ensuring broad engagement
from the outset may help mitigate these
issues by identifying priority areas specif-
ic to particular countries. Stakeholders
can conduct current-state assessments
for future innovations to determine the
impact, both positive and negative, of

artificial intelligence diagnostic imple-
mentation, and decide how and if such
innovations can be used locally and the
appropriate timing of implementation.

Image-based artificial intelligence
for the diagnoses of neglected tropical
diseases has the potential to transform
health care in low- and middle-income
countries affected by these diseases.
While this field is still in its early stages,
there is potential to bring quality di-
agnostic tools to clinical and public
health settings in the most underserved
regions. As this field evolves, integrating
an ethical framework for the develop-
ment of these tools will enable their sus-
tainability and utility. Broad stakeholder
engagement, a focus on consent and data
security, and balancing the use of limited
public health resources are important
principles that can be introduced early
in the development of this technology.
Doing so will ensure the most impactful
use of artificial intelligence diagnoses
for neglected tropical diseases and its
ultimate long-term success and sustain-
ability. ■

Acknowledgements
NL is also affiliated with the Institute for
Molecular Medicine Finland, University
of Helsinki, Helsinki, Finland.

Competing interests: None declared.

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THE BELMONT REPORT
Office of the Secretary
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
April 18, 1979

AGENCY: Department of Health, Education, and Welfare.

ACTION: Notice of Report for Public Comment.

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

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

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

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.

Robert E. Cooke, M.D., President, Medical College of Pennsylvania.

Dorothy I. Height, President, National Council of Negro Women, Inc.

Albert R. Jonsen, Ph.D., Associate Professor of Bioethics, University of California at San Francisco.

Patricia King, J.D., Associate Professor of Law, Georgetown University Law Center.

Karen Lebacqz, Ph.D., Associate Professor of Christian Ethics, Pacific School of Religion.

*** David W. Louisell, J.D., Professor of Law, University of California at Berkeley.

Donald W. Seldin, M.D., Professor and Chairman, Department of Internal Medicine, University of Texas at

Dallas.

*** Eliot Stellar, Ph.D., Provost of the University and Professor of Physiological Psychology, University of

Pennsylvania.

*** Robert H. Turtle, LL.B., Attorney, VomBaur, Coburn, Simmons & Turtle, Washington, D.C.
*** Deceased.

Table of Contents
Ethical Principles and Guidelines for Research Involving Human Subjects

A. Boundaries Between Practice and Research

B. Basic Ethical Principles

1. Respect for Persons

2. Beneficence

3. Justice

C. Applications

1. Informed Consent

2. Assessment of Risk and Benefits

3. Selection of Subjects

Ethical Principles & 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 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 [1] 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.

Part A: Boundaries Between Practice & Research
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 [2]. 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 [3].

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.

Part B: Basic Ethical Principles
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 of 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 consequence. 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 flagrant 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.

Part C: Applications
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 disable 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 harm 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 …