NCM 108: Health Care Ethics
Module 4: Bioethics & Research
NURUMBERG CODE
The Nuremberg Code and its impact on clinical
research
- The Nuremberg Code is one of the most
influential documents in the history of clinical
research.
- Created more than 70 years ago following the
notorious World War II experiments, this written
document established 10 ethical principles for
protecting human subjects.
What Is the Nuremberg Code?
When World War II ended in 1945, the victorious Allied
powers enacted the International Military Tribunal on
November 19th, 1945. As part of the Tribunal, a series
of trials were held against major war criminals and Nazi
sympathizers holding leadership positions in political,
military, and economic areas. The first trial conducted
under the Nuremberg Military Tribunals in 1947 became
known as The Doctors’ Trial, in which 23 physicians from
the German Nazi Party were tried for crimes against
humanity for the atrocious experiments they carried out
on unwilling prisoners of war. Many of the grotesque
medical experiments took place at the Auschwitz
concentration camp, where Jewish prisoners were
tattooed with dehumanizing numbers onto their arms;
numbers that would later be used to identify their bodies
after death.
The Doctors’ Trial is officially titled “The United States of
America v. Karl Brandt, et al.,” and it was conducted at
the Palace of Justice in Nuremberg, Bavaria, Germany.
The trial was conducted here because this was one of
the few largely undamaged buildings that remained
intact from extensive Allied bombing during the war. It
is also said to have been symbolically chosen because it
was the ceremonial birthplace of the Nazi Party. Of the
23 defendants, 16 were found guilty, of which seven
received death sentences and nine received prison
sentences ranging from 10 years to life imprisonment.
The other 7 defendants were acquitted.
The verdict also resulted in the creation of the
Nuremberg Code, a set of ten ethical principles for
human experimentation.
What Are The Nuremberg Code’s Ethical Guidelines
For Research?
The Nuremberg Code aimed to protect human subjects
from enduring the kind of cruelty and exploitation the
prisoners endured at concentration camps. The 10
elements of the code are:
1. Voluntary consent is essential
2. The results of any experiment must be for the
greater good of society
3. Human experiments should be based on previous
animal experimentation
4. Experiments should be conducted by avoiding
physical/mental suffering and injury
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5. No experiments should be conducted if it is
believed to cause death/disability
6. The risks should never exceed the benefits
7. Adequate facilities should be used to protect
subjects
8. Experiments should be conducted only by qualified
scientists
9. Subjects should be able to end their participation at
any time
10. The scientist in charge must be prepared to
terminate the experiment when injury, disability, or
death is likely to occur
The Significance Of The Nuremberg Code
The Nuremberg Code is one of several foundational
documents that influenced the principles of Good
Clinical Practice (GCP).
Good Clinical Practice is an attitude of excellence in
research that provides a standard for study design,
implementation, conduct and analysis. More than a
single document, it is a compilation of many thoughts,
ideas and lessons learned throughout the history of
clinical research worldwide.
Several other documents further expanded upon the
principles outlined in the Nuremberg Code, including the
Declaration of Helsinki, the Belmont Report and the
Common Rule.
Although there has been updated guidance to Good
Clinical Practice to reflect new trends and technologies,
such as electronic signatures, these basic principles
remain the same. The goal has always been—and
always will be—to conduct ethical clinical trials and
protect human subjects.
The History of Clinical Research Timeline (by IMARC
Research)
● 1974 - FDA Bureau of MEdical Devices and
DIasgnostic Products
● 1932-1972 - The Tuskegee Syphilis Study
● 1939-1945 - World War 2 Experiments
● 1951 - Henrietta Lacks
● 1974 - The National Research Act
● 1979 - The Belmont Report
● 1999 - IMARC Research, INC
Fifty Years Later: The Significance of the Nuremberg
Code
The voluntary consent of the human subject is
absolutely essential.
1. This means that the person involved should have
legal capacity to give consent; should be so situated
as to be able to exercise free power of choice,
without the intervention of any element of force,
fraud, deceit, duress, overreaching, or other ulterior
form of constraint or coercion; and should have
sufficient knowledge and comprehension of the
elements of the subject matter involved as to
enable him to make an understanding and
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enlightened decision. This latter element requires
that before the acceptance of an affirmative decision
by the experimental subject there should be made
known to him the nature, duration, and purpose of
the experiment; the method and means by which it
is to be conducted; all inconveniences and hazards
reasonably to be expected; and the effects upon his
health or person which may possibly come from his
participation in the experiment.
The duty and responsibility for ascertaining the
quality of the consent rests upon each individual
who initiates, directs or engages in the experiment.
It is a personal duty and responsibility which may
not be delegated to another with impunity.
2. The experiment should be such as to yield fruitful
results for the good of society, unprocurable by
other methods or means of study, and not random
and unnecessary in nature.
3. The experiment should be so designed and based
on the results of animal experimentation and a
knowledge of the natural history of the disease or
other problem under study that the anticipated
results will justify the performance of the
experiment.
4. The experiment should be so conducted as to avoid
all unnecessary physical and mental suffering and
injury.
5. No experiment should be conducted where there is
an a priori reason to believe that death or disabling
injury will occur; except, perhaps, in those
experiments where the experimental physicians
also serve as subjects.
6. The degree of risk to be taken should never exceed
that determined by the humanitarian importance of
the problem to be solved by the experiment.
7. Proper preparations should be made and adequate
facilities provided to protect the experimental
subject against even remote possibilities of injury,
disability, or death.
8. The experiment should be conducted only by
scientifically qualified persons. The highest degree
of skill and care should be required through all
stages of the experiment of those who conduct or
engage in the experiment.
9. During the course of the experiment the human
subject should be at liberty to bring the experiment
to an end if he has reached the physical or mental
state where continuation of the experiment seems
to him to be impossible.
10. During the course of the experiment the scientist in
charge must be prepared to terminate the
experiment at any stage, if he has probable cause to
believe, in the exercise of the good faith, superior
skill, and careful judgment required of him, that a
continuation of the experiment is likely to result in
injury, disability, or death to the experimental
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subject.
The Doctors' Trial
● The main trial at Nuremberg after World War II was
conducted by the International Military Tribunal.
● The tribunal was made up of judges from the four
allied powers (the United States, Britain, France,
and the former Soviet Union) and was charged with
trying Germany's major war criminals.
● The first of these trials, the Doctors' Trial, involved
23 defendants, all but 3 of whom were physicians
accused of murder and torture in the conduct of
medical experiments on concentration-camp
inmates.
● October 25, 1946 - the indictment of the
defendants 25 days after the conclusion of the first
Nuremberg trial by the International Military
Tribunal.
● The Doctors' Trial began on December 9, 1946, and
ended on July 19, 1947.
● The case was heard by three judges and one
alternate.
● Thirty-two prosecution witnesses and 53 defense
witnesses, including the 23 defendants, testified. A
total of 1471 documents were introduced into the
record. Sixteen of the 23 defendants were found
guilty; 7 of them were sentenced to death by
hanging, 5 to life imprisonment, 2 to imprisonment
for 25 years, 1 to imprisonment for 15 years, and 1
to imprisonment for 10 years. Seven were acquitted.
TELFORD TAYLOR
● the trial was a murder trial (and murder had been
identified by the International Military Tribunal as a
crime against humanity)
● this was “no mere murder trial,” because the
defendants were physicians who had sworn to “do
no harm” and to abide by the Hippocratic Oath.
● One recurring theme was the relevance of
Hippocratic ethics to human experimentation and
whether Hippocratic moral ideals could be an
exclusive guide to the ethics of research without
risk to the human rights of subjects.
In the trial's exploration of ideas that shaped
medical-research ethics, three physicians had central
roles: Leo Alexander, an American neuropsychiatrist,
Werner Leibbrand, a German psychiatrist and medical
historian, and Andrew Ivy, a renowned American
physiologist.
LEO ALEXANDER
● Viennese-born American physician, had joined the
U.S. Army Medical Corps in 1942
● At the end of the war, Alexander was sent on a
special mission under the Combined Intelligence
Objectives Sub-Committee, an intelligence
organization with members from several nations,
and charged by orders from Supreme Headquarters
of Allied Expeditionary Forces to gather evidence
for the Nuremberg trials.
● 2 days before the opening of the Doctors' Trial -
Alexander gave Taylor a memorandum entitled
“Ethical and Non-Ethical Experimentation on
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Human Beings,” in which he identified three ethical,
legal, and scientific requirements for the conduct of
human experimentation.
● April 15, 1947 - Alexander gave Taylor a second
memorandum.
WERNER LEIBBRAND
● German psychiatrist and medical historian at
Erlangen University
● January 27, 1947 - opened the debate on medical
ethics at Nuremberg.
● German physicians at the beginning of the 20th
century had adopted a “biologic thinking” according
to which a patient was a series of biologic events,
and nothing more than “a mere object, like a mail
package.
● He strongly condemned physicians who conducted
experiments on subjects without their consent, and
testified that this was also the result of biologic
thinking.
● During cross-examination, defense lawyers
asserted that “civilized” nations such as France, the
Netherlands, Britain, and the United States had
performed dangerous medical experiments on
prisoners, often without their consent.
● Defense lawyers explained that Nazi doctors were
ordered by the state to conduct such experiments
as the high-altitude, hypothermia, and seawater
experiments on inmates at the Dachau
concentration camp to determine how best to
protect and treat German fliers and soldiers.
● Once these physiologic experiments became the
centerpiece of the trial, reliance on psychiatrists
alone was not possible.
ANDREW IVY
● internationally known physiologist and a noted
scientist.
● first-hand knowledge of the Stateville Penitentiary
experiments on malaria
● June 12, 1947 - testify in rebuttal for the
prosecution.
● December 1946 - His document entitled “Principles
of Ethics Concerning Experimentation with Human
Beings,” adopted by the American Medical
Association House of Delegates.
● Ivy explaine that these common-sense principles
mirrored the understanding shared by everyone in
practice in the medical community.
● first principle was that a physician would never do
anything to a patient or subject before obtaining his
or her consent.
Medical Ethics and Human Rights
The judges at Nuremberg, although they realized the
importance of Hippocratic ethics and the maxim primum
non nocere, recognized that more was necessary to
protect human research subjects. Accordingly, the judges
articulated a sophisticated set of 10 research principles
centered not on the physician but on the research
subject. These principles, which we know as the
Nuremberg Code, included a new, comprehensive, and
absolute requirement of informed consent (principle 1),
and a new right of the subject to withdraw from
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participation in an experiment (principle 9). The judges
adopted much of the language proposed by Alexander
and Ivy but were more emphatic about the necessity and
attributes of the subject's consent and explicitly added
the subject's right to withdraw.
In the traditional Hippocratic doctor–patient relationship,
the patient is silent and dutifully obedient to the
beneficent and trusted physician.16-18 Obviously, the
patient must seek the physician's help and initiate the
therapeutic relationship with the physician.17 But once
patients agree to be treated, they trust that the physician
will act in their interest, or at least will do no harm.17,18
In research, which is outside the beneficent context of
the physician–patient relationship, this trust may be
misplaced, because the physician's primary goal is not to
treat; rather, it is to test a scientific hypothesis by
following a protocol, regardless of the patient-subject's
best interest. It is therefore only through a conflation of
treatment and research that Alexander and Ivy believed
they could expand on Hippocratic ethics to protect the
rights of subjects in human experimentation.19,20 Their
Hippocratic view of medical research may have
prevented them from adequately appreciating the risks
to research subjects, which are many times greater than
the risks to patients who are merely being treated.21
Hippocratic ethics, even when supplemented with
informed consent, tend to submerge the subject's
autonomy into what the physician-investigator thinks is
best for the subject.
Informed consent, the core of the Nuremberg Code, has
rightly been viewed as the protection of subjects' human
rights. The key contribution of Nuremberg was to merge
Hippocratic ethics and the protection of human rights
into a single code. The Nuremberg Code not only
requires that physician-researchers protect the best
interests of their subjects (principles 2 through 8 and 10)
but also proclaims that subjects can actively protect
themselves as well (principles 1 and 9). Most strikingly,
for example, in Hippocratic ethics the subject relies on
the physician to determine when it is in the subject's best
interest to end his or her participation in an experiment.
In the Nuremberg Code, the judges gave the subject as
much authority as the physician-researcher to end the
experiment before its conclusion (principle 9).
50 Years after Nuremberg
The Nuremberg Code has not been officially adopted in
its entirety as law by any nation or as ethics by any major
medical association. Nonetheless, its influence on global
human-rights law and medical ethics has been
profound.6 Its basic requirement of informed consent, for
example, has been universally accepted and is
articulated in international law in Article 7 of the United
Nations International Covenant on Civil and Political
Rights (1966).6,22 Informed consent, with specific
reliance on the Nuremberg Code, is also the basis of the
International Ethical Guidelines for Biomedical Research
Involving Human Subjects, the most recent guidelines
promulgated by the World Health Organization and the
Council for International Organizations of Medical
Sciences (1993).23
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The World Medical Association, established during
World War II, has been accused of purposely trying to
undermine Nuremberg in order to distance physicians
from Nazi medical crimes.24 The election of a former
Nazi physician and SS member, Hans-Joachim Sewering,
to the presidency of that organization in 1992 added
credibility to that accusation.24 (Because of public
criticism, Sewering later withdrew.) Nonetheless, the
various versions of the Declaration of Helsinki
promulgated by the World Medical Association since
1964, although attempting to have peer review
supplement informed consent and even supplant it as
their central principle in the context of “therapeutic
research,” all implicitly acknowledge Nuremberg's
authority. Both the Nuremberg Code and the Declaration
of Helsinki served as models for the current U.S. federal
research regulations, which require not only the informed
consent of the research subject (with proxy consent
sometimes acceptable, as for young children), but also
prior peer review of research protocols by a committee
(the institutional review board of the hospital or research
institution) that includes a representative of the
community.25
The Nuremberg Code focuses on the human rights of
research subjects, the Declaration of Helsinki focuses on
the obligations of physician-investigators to research
subjects, and the federal regulations emphasize the
obligations of research institutions that receive federal
funds. Nonetheless, by insisting that medical
investigators alone cannot set the rules for the ethical
conduct of research, even when guided by beneficence
and Hippocratic ethics, and by adopting a human-rights
perspective that acknowledges the centrality of informed
consent and the right of the subject to withdraw, the
Nuremberg Code has changed forever the way both
physicians and the public view the proper conduct of
medical research on human subjects. Fifty years after
Nuremberg, we recognize the human-rights legacy of the
Nuremberg Code and are better able to face the critical
challenge of applying the Code in its entirety and
enforcing its human-rights provisions.
Why is the Nuremberg Code being used to oppose
Covid-19 vaccines?
● The Nuremberg Code is a set of ethical research
principles, developed in the wake of Nazi
atrocities—specifically the inhumane and often fatal
experimentation on human subjects without
consent—during World War Two.
What is the Nuremberg Code?
● Created in 1947 in Nuremberg, Germany,
● was developed in response to the horrors of this
experimentation, with the aim of protecting human
subjects in medical research.
● The Code, and particularly its emphasis on informed
consent, has had a profound impact on international
human rights law and medical ethics.
The Nuremberg Code and Covid-19 vaccines
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● Covid-19 vaccines violate the Nuremberg Code
because they are somehow “experimental” and, as
people receiving the vaccines are not made aware
of this, they are unable to give their informed
consent.
● This claim that the Covid-19 vaccines are
experimental is simply not true, and something we
have corrected multiple times.
● Dr Alexis Paton - lecturer in social epidemiology
and the sociology of health at Aston University,
Birmingham.
● Nuremberg Code is “very specifically about
experimentation” (Dr Alexis Paton)
● Informed consent is still required for those receiving
the Covid-19 or any other vaccine.
● Professor Emma Cave - professor of healthcare law
at Durham University, explained that the need for
this does not come from the Nuremberg Code.
● Arguments that the vaccines are experimental
usually hinge on the fact that data is being
collected on any side effects in recipients, although
it is normal that authorities continue to monitor the
safety of all vaccines once they are approved.
● Dr Julian Sheather - special advisor in ethics and
human rights to the British Medical Association.
told Full Fact it would be “impossible” and
“unethical” to roll out any medical intervention
without collecting data on it.
“Morally grotesque”
● It is important to note that the Nuremberg Code is
not the only set of ethical guidelines for human
experimentation.
● what is specific to the Nuremberg Code is the direct
association with the atrocities committed by the
Nazis during World War Two, and the emotional
response this triggers.
● Misinformation thrives when feelings are
manipulated in this way, as claims which create an
emotional response are most likely to be shared.
BELMONT REPORT
The Belmont Report: What is it and how does it relate
to today’s clinical trials?
● The quest to discover effective treatments and
cures for diseases and conditions is a worthwhile
and compelling goal.
● The Belmont Report identifies basic ethical
principles for conducting research that involve
human subjects.
History of the Belmont Report
● The need for ethical principles first arose as a result
of the reported atrocities inflicted on human
subjects during World War II.
● During the Nuremberg War Crime Trials, the
Nuremberg Cod
● e was drafted that set forth standards used to judge
physicians and scientists who conducted biomedical
experiments on concentration camp prisoners.
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● The Nuremberg Code set the example for
subsequent codes that established rules to help
protect human subjects involved in research.
● To avoid the limitations of these past codes, the
Belmont Report was deliberately broader and
established 3 basic ethical principles:
1. Respect for persons
2. Beneficence
3. Justice
The 3 Basic Ethical Principles and Their Applicability
to Clinical Trials
Respect for Persons
● made up of 2 important but distinct requirements.:
○ The first is the recognition that people are
autonomous and entitled to their own opinions
and choices, unless detrimental to others.
○ The second is the recognition that due to
various reasons, not all people are capable of
self-determination and instead require
protection.
Beneficence
● recognition that people are treated in an ethical
manner not only by respecting their decisions and
protecting them from harm
● The Belmont Report identifies 2 general and
complementary rules regarding beneficence:
○ Do not harm
○ Maximize possible benefits and minimize
possible harms
Justice
● raises questions about who ought to receive the
benefits of research and who ought to bear its
burdens.
● the principle of justice may demand scrutiny of
whether classes of people considered compromised
or vulnerable are excluded from participation in
clinical trials due to financial and other barriers even
though they have a connection to the problem
being considered.
BELMONT PRINCIPLES
Respect for Persons - Treat individuals as autonomous
human beings, capable of making their own decisions
and choices, and do not use people as a means to an end
Three Requirements Based on Respect for Persons
- obtain and document informed consent
- respect the privacy interests of research subjects
- consider additional protection when conducting
research on individuals with limited autonomy
Beneficence - Minimize the risks of harm and maximize
the potential benefits
Five Requirements Based on Beneficence
- use procedures that present the least risk to
subjects consistent with answering the scientific
question
- gather data from procedures or activities that are
already being performed for non-research
reasons
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- risks to subjects should be reasonable in relation
to both the potential benefits to the subjects and
the importance of the knowledge expected to
result
- maintain promises of confidentiality
- monitor the data to ensure the safety of subjects
Justice - treat people fairly and design research so that
its burdens and benefits are shared equitably
Two Requirements Based on Justice
- select subjects equitably
- avoid exploitation of vulnerable populations or
populations of convenience
Rationale for an Institutional Review Board (IRB)
The ethical principles and federal regulation generated
by the Belmont Report provide a framework for IRBs to
evaluate research involving human subjects. An objective
review of research is necessary because
1. some researchers focused on their goals may
unintentionally overlook other implications or
aspects of their work and
2. no one can be totally objective about his or her own
work.
The IRB review system is designed to provide an
independent, objective review of research involving
human subjects so that the privilege of conducting
human subjects research may be maintained.
Research is a …
● systematic investigation (this might range from
applying scientific methodology involving
independent and dependent variables to an
ethnographic study of a community)
● including research development, testing, and
evaluation (this also includes pilot studies,
feasibility studies, and other preliminary studies)
● designed to develop or contribute to generalizable
knowledge (An essential consideration is whether it
is the intention of the investigator to contribute to
generalizable knowledge.
Some activities that involve interactions with humans
and data gathering many not fit the definition of research
with human subjects. Always check with the IRB.
A human subject is a …
“living individual" about whom an investigator (whether
professional or student) conducting research obtains:
1. Data through intervention or interaction (does not
need to be face-to-face, could be via email or a
participant observation) with the individual or
2. Identifiable private information
a. information about behaviors that occur in a
context where the individual can reasonably
expect that no observations or recording is
taking place or
b. information that is provided for a specific
purpose and for which the individual can
reasonably expect will not be made public.
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DECLARATION OF HELSINKI
WMA DECLARATION OF HELSINKI – ETHICAL
PRINCIPLES FOR MEDICAL RESEARCH INVOLVING
HUMAN SUBJECTS
● Adopted by the 18th WMA General Assembly,
Helsinki, Finland, June 1964 and amended by the:
● 29th WMA General Assembly, Tokyo, Japan,
October 1975
● 35th WMA General Assembly, Venice, Italy,
October 1983
● 41st WMA General Assembly, Hong Kong,
September 1989
● 48th WMA General Assembly, Somerset West,
Republic of South Africa, October 1996
● 52nd WMA General Assembly, Edinburgh,
Scotland, October 2000
● 53rd WMA General Assembly, Washington DC,
USA, October 2002 (Note of Clarification added)
● 55th WMA General Assembly, Tokyo, Japan,
October 2004 (Note of Clarification added)
● 59th WMA General Assembly, Seoul, Republic of
Korea, October 2008
● 64th WMA General Assembly, Fortaleza, Brazil,
October 2013
PREAMBLE
1. The World Medical Association (WMA) has
developed the Declaration of Helsinki as a
statement of ethical principles for medical research
involving human subjects, including research on
identifiable human material and data.
The Declaration is intended to be read as a whole
and each of its constituent paragraphs should be
applied with consideration of all other relevant
paragraphs.
2. Consistent with the mandate of the WMA, the
Declaration is addressed primarily to physicians.
The WMA encourages others who are involved in
medical research involving human subjects to adopt
these principles.
GENERAL PRINCIPLES
3. The Declaration of Geneva of the WMA binds the
physician with the words, “The health of my patient
will be my first consideration,” and the International
Code of Medical Ethics declares that, “A physician
shall act in the patient’s best interest when
providing medical care.”
4. It is the duty of the physician to promote and
safeguard the health, well-being and rights of
patients, including those who are involved in
medical research. The physician’s knowledge and
conscience are dedicated to the fulfilment of this
duty.
5. Medical progress is based on research that
ultimately must include studies involving human
subjects.
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6. The primary purpose of medical research involving
human subjects is to understand the causes,
development and effects of diseases and improve
preventive, diagnostic and therapeutic interventions
(methods, procedures and treatments). Even the
best proven interventions must be evaluated
continually through research for their safety,
effectiveness, efficiency, accessibility and quality.
7. Medical research is subject to ethical standards that
promote and ensure respect for all human subjects
and protect their health and rights.
8. While the primary purpose of medical research is to
generate new knowledge, this goal can never take
precedence over the rights and interests of
individual research subjects.
9. It is the duty of physicians who are involved in
medical research to protect the life, health, dignity,
integrity, right to self-determination, privacy, and
confidentiality of personal information of research
subjects. The responsibility for the protection of
research subjects must always rest with the
physician or other health care professionals and
never with the research subjects, even though they
have given consent.
10. Physicians must consider the ethical, legal and
regulatory norms and standards for research
involving human subjects in their own countries as
well as applicable international norms and
standards. No national or international ethical, legal
or regulatory requirement should reduce or
eliminate any of the protections for research
subjects set forth in this Declaration.
11. Medical research should be conducted in a manner
that minimises possible harm to the environment.
12. Medical research involving human subjects must be
conducted only by individuals with the appropriate
ethics and scientific education, training and
qualifications. Research on patients or healthy
volunteers requires the supervision of a competent
and appropriately qualified physician or other
health care professional.
13. Groups that are underrepresented in medical
research should be provided appropriate access to
participation in research.
14. Physicians who combine medical research with
medical care should involve their patients in
research only to the extent that this is justified by
its potential preventive, diagnostic or therapeutic
value and if the physician has good reason to
believe that participation in the research study will
not adversely affect the health of the patients who
serve as research subjects.
15. Appropriate compensation and treatment for
subjects who are harmed as a result of participating
in research must be ensured.
Risks, Burdens and Benefits
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16. In medical practice and in medical research, most
interventions involve risks and burdens.
Medical research involving human subjects may
only be conducted if the importance of the objective
outweighs the risks and burdens to the research
subjects.
17. All medical research involving human subjects must
be preceded by careful assessment of predictable
risks and burdens to the individuals and groups
involved in the research in comparison with
foreseeable benefits to them and to other
individuals or groups affected by the condition
under investigation.
Measures to minimise the risks must be
implemented. The risks must be continuously
monitored, assessed and documented by the
researcher.
18. Physicians may not be involved in a research study
involving human subjects unless they are confident
that the risks have been adequately assessed and
can be satisfactorily managed.
When the risks are found to outweigh the potential
benefits or when there is conclusive proof of
definitive outcomes, physicians must assess
whether to continue, modify or immediately stop
the study.
Vulnerable Groups and Individuals
19. Some groups and individuals are particularly
vulnerable and may have an increased likelihood of
being wronged or of incurring additional harm.
All vulnerable groups and individuals should
receive specifically considered protection.
20. Medical research with a vulnerable group is only
justified if the research is responsive to the health
needs or priorities of this group and the research
cannot be carried out in a non-vulnerable group. In
addition, this group should stand to benefit from the
knowledge, practices or interventions that result
from the research.
Scientific Requirements and Research Protocols
21. Medical research involving human subjects must
conform to generally accepted scientific principles,
be based on a thorough knowledge of the scientific
literature, other relevant sources of information, and
adequate laboratory and, as appropriate, animal
experimentation. The welfare of animals used for
research must be respected.
22. The design and performance of each research study
involving human subjects must be clearly described
and justified in a research protocol.
The protocol should contain a statement of the
ethical considerations involved and should indicate
how the principles in this Declaration have been
addressed. The protocol should include information
regarding funding, sponsors, institutional
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affiliations, potential conflicts of interest, incentives
for subjects and information regarding provisions
for treating and/or compensating subjects who are
harmed as a consequence of participation in the
research study.
In clinical trials, the protocol must also describe
appropriate arrangements for post-trial provisions.
Research Ethics Committees
23. The research protocol must be submitted for
consideration, comment, guidance and approval to
the concerned research ethics committee before the
study begins. This committee must be transparent
in its functioning, must be independent of the
researcher, the sponsor and any other undue
influence and must be duly qualified. It must take
into consideration the laws and regulations of the
country or countries in which the research is to be
performed as well as applicable international
norms and standards but these must not be
allowed to reduce or eliminate any of the
protections for research subjects set forth in this
Declaration.
The committee must have the right to monitor
ongoing studies. The researcher must provide
monitoring information to the committee, especially
information about any serious adverse events. No
amendment to the protocol may be made without
consideration and approval by the committee. After
the end of the study, the researchers must submit a
final report to the committee containing a summary
of the study’s findings and conclusions.
Privacy and Confidentiality
24. Every precaution must be taken to protect the
privacy of research subjects and the confidentiality
of their personal information.
Informed Consent
25. Participation by individuals capable of giving
informed consent as subjects in medical research
must be voluntary. Although it may be appropriate
to consult family members or community leaders,
no individual capable of giving informed consent
may be enrolled in a research study unless he or
she freely agrees.
26. In medical research involving human subjects
capable of giving informed consent, each potential
subject must be adequately informed of the aims,
methods, sources of funding, any possible conflicts
of interest, institutional affiliations of the researcher,
the anticipated benefits and potential risks of the
study and the discomfort it may entail, post-study
provisions and any other relevant aspects of the
study. The potential subject must be informed of
the right to refuse to participate in the study or to
withdraw consent to participate at any time without
reprisal. Special attention should be given to the
specific information needs of individual potential
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subjects as well as to the methods used to deliver
the information.
After ensuring that the potential subject has
understood the information, the physician or
another appropriately qualified individual must then
seek the potential subject’s freely-given informed
consent, preferably in writing. If the consent cannot
be expressed in writing, the non-written consent
must be formally documented and witnessed.
All medical research subjects should be given the
option of being informed about the general outcome
and results of the study.
27. When seeking informed consent for participation in
a research study the physician must be particularly
cautious if the potential subject is in a dependent
relationship with the physician or may consent
under duress. In such situations the informed
consent must be sought by an appropriately
qualified individual who is completely independent
of this relationship.
28. For a potential research subject who is incapable of
giving informed consent, the physician must seek
informed consent from the legally authorised
representative. These individuals must not be
included in a research study that has no likelihood
of benefit for them unless it is intended to promote
the health of the group represented by the potential
subject, the research cannot instead be performed
with persons capable of providing informed
consent, and the research entails only minimal risk
and minimal burden.
29. When a potential research subject who is deemed
incapable of giving informed consent is able to give
assent to decisions about participation in research,
the physician must seek that assent in addition to
the consent of the legally authorised representative.
The potential subject’s dissent should be respected.
30. Research involving subjects who are physically or
mentally incapable of giving consent, for example,
unconscious patients, may be done only if the
physical or mental condition that prevents giving
informed consent is a necessary characteristic of the
research group. In such circumstances the physician
must seek informed consent from the legally
authorised representative. If no such representative
is available and if the research cannot be delayed,
the study may proceed without informed consent
provided that the specific reasons for involving
subjects with a condition that renders them unable
to give informed consent have been stated in the
research protocol and the study has been approved
by a research ethics committee. Consent to remain
in the research must be obtained as soon as
possible from the subject or a legally authorised
representative.
31. The physician must fully inform the patient which
aspects of their care are related to the research. The
refusal of a patient to participate in a study or the
11/16/22
patient’s decision to withdraw from the study must
never adversely affect the patient-physician
relationship.
32. For medical research using identifiable human
material or data, such as research on material or
data contained in biobanks or similar repositories,
physicians must seek informed consent for its
collection, storage and/or reuse. There may be
exceptional situations where consent would be
impossible or impracticable to obtain for such
research. In such situations the research may be
done only after consideration and approval of a
research ethics committee.
Use of Placebo
33. The benefits, risks, burdens and effectiveness of a
new intervention must be tested against those of
the best proven intervention(s), except in the
following circumstances:
Where no proven intervention exists, the use of
placebo, or no intervention, is acceptable; or
Where for compelling and scientifically sound
methodological reasons the use of any intervention
less effective than the best proven one, the use of
placebo, or no intervention is necessary to
determine the efficacy or safety of an intervention
and the patients who receive any intervention less
effective than the best proven one, placebo, or no
intervention will not be subject to additional risks of
serious or irreversible harm as a result of not
receiving the best proven intervention.
Extreme care must be taken to avoid abuse of this
option.
Post-Trial Provisions
34. In advance of a clinical trial, sponsors, researchers
and host country governments should make
provisions for post-trial access for all participants
who still need an intervention identified as
beneficial in the trial. This information must also be
disclosed to participants during the informed
consent process.
Research Registration and Publication and
Dissemination of Results
35. Every research study involving human subjects
must be registered in a publicly accessible database
before recruitment of the first subject.
36. Researchers, authors, sponsors, editors and
publishers all have ethical obligations with regard
to the publication and dissemination of the results
of research. Researchers have a duty to make
publicly available the results of their research on
human subjects and are accountable for the
completeness and accuracy of their reports. All
parties should adhere to accepted guidelines for
ethical reporting. Negative and inconclusive as well
as positive results must be published or otherwise
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Module 4: Bioethics & Research

made publicly available. Sources of funding,

institutional affiliations and conflicts of interest
must be declared in the publication. Reports of
research not in accordance with the principles of
this Declaration should not be accepted for
publication.

Unproven Interventions in Clinical Practice

37. In the treatment of an individual patient, where

proven interventions do not exist or other known
interventions have been ineffective, the physician,
after seeking expert advice, with informed consent
from the patient or a legally authorised
representative, may use an unproven intervention if
in the physician’s judgement it offers hope of saving
life, re-establishing health or alleviating suffering.
This intervention should subsequently be made the
object of research, designed to evaluate its safety
and efficacy. In all cases, new information must be
recorded and, where appropriate, made publicly
available.

Declaration of Helsinki (1964)

Declaration of Helsinki
- formal statement of ethical principles published by
the World Medical Association (WMA)
- to guide the protection of human participants in
medical research.
- was adopted in 1964 by the 18th WMA General
Assembly, at Helsinki.

Origins and early revisions