| Ethical Principles for Medical Research Involving
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; and the 52nd WMA General Assembly,
Edinburgh, Scotland, October 2000. Note of Clarification
on Paragraph 29 added by the WMA General Assembly, Washington
||The World Medical Association has developed the Declaration
of Helsinki as a statement of ethical principles to
provide guidance to physicians and other participants
in medical research involving human subjects. Medical
research involving human subjects includes research
on identifiable human material or identifiable data.
|| It is the duty of the physician to promote and safeguard
the health of the people. The physician’s knowledge
and conscience are dedicated to the fulfillment of
||The Declaration of Geneva of the World Medical Association
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 only in the patient's interest
when providing medical care which might have the effect
of weakening the physical and mental condition of the
|| Medical progress is based on research which ultimately
must rest in part on experimentation involving human
||In medical research on human subjects, considerations
related to the well-being of the human subject should
take precedence over the interests of science and society.
||The primary purpose of medical research involving
human subjects is to improve prophylactic, diagnostic
and therapeutic procedures and the understanding of
the aetiology and pathogenesis of disease. Even the
best proven prophylactic, diagnostic, and therapeutic
methods must continuously be challenged through research
for their effectiveness, efficiency, accessibility
||In current medical practice and in medical research,
most prophylactic, diagnostic and therapeutic procedures
involve risks and burdens.
|| Medical research is subject to ethical standards
that promote respect for all human beings and protect
their health and rights. Some research populations
are vulnerable and need special protection. The particular
needs of the economically and medically disadvantaged
must be recognized. Special attention is also required
for those who cannot give or refuse consent for themselves,
for those who may be subject to giving consent under
duress, for those who will not benefit personally from
the research and for those for whom the research is
combined with care.
||Research Investigators should be aware of the ethical,
legal and regulatory requirements for research on human
subjects in their own countries as well as applicable
international requirements. No national ethical, legal
or regulatory requirement should be allowed to reduce
or eliminate any of the protections for human subjects
set forth in this Declaration.
B. BASIC PRINCIPLES FOR ALL MEDICAL RESEARCH
||It is the duty of the physician in medical research
to protect the life, health, privacy, and dignity of
the human subject.
|| 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 on adequate
laboratory and, where appropriate, animal experimentation.
||Appropriate caution must be exercised in the conduct
of research which may affect the environment, and the
welfare of animals used for research must be respected.
|| The design and performance of each experimental
procedure involving human subjects should be clearly
formulated in an experimental protocol. This protocol
should be submitted for consideration, comment, guidance,
and where appropriate, approval to a specially appointed
ethical review committee, which must be independent
of the investigator, the sponsor or any other kind
of undue influence. This independent committee should
be in conformity with the laws and regulations of the
country in which the research experiment is performed.
The committee has the right to monitor ongoing trials.
The researcher has the obligation to provide monitoring
information to the committee, especially any serious
adverse events. The researcher should also submit to
the committee, for review, information regarding funding,
sponsors, institutional affiliations, other potential
conflicts of interest and incentives for subjects.
||The research protocol should always contain a statement
of the ethical considerations involved and should indicate
that there is compliance with the principles enunciated
in this Declaration.
||Medical research involving human subjects should
be conducted only by scientifically qualified persons
and under the supervision of a clinically competent
medical person. The responsibility for the human subject
must always rest with a medically qualified person
and never rest on the subject of the research, even
though the subject has given consent.
||Every medical research project involving human subjects
should be preceded by careful assessment of predictable
risks and burdens in comparison with foreseeable benefits
to the subject or to others. This does not preclude
the participation of healthy volunteers in medical
research. The design of all studies should be publicly
|| Physicians should abstain from engaging in research
projects involving human subjects unless they are confident
that the risks involved have been adequately assessed
and can be satisfactorily managed. Physicians should
cease any investigation if the risks are found to outweigh
the potential benefits or if there is conclusive proof
of positive and beneficial results.
|| Medical research involving human subjects should
only be conducted if the importance of the objective
outweighs the inherent risks and burdens to the subject.
This is especially important when the human subjects
are healthy volunteers.
||Medical research is only justified if there is a
reasonable likelihood that the populations in which
the research is carried out stand to benefit from the
results of the research.
||The subjects must be volunteers and informed participants
in the research project.
||The right of research subjects to safeguard their
integrity must always be respected. Every precaution
should be taken to respect the privacy of the subject,
the confidentiality of the patient’s information
and to minimize the impact of the study on the subject's
physical and mental integrity and on the personality
of the subject.
||In any research on human beings, 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. The subject should be informed of the
right to abstain from participation in the study or
to withdraw consent to participate at any time without
reprisal. After ensuring that the subject has understood
the information, the physician should then obtain the
subject's freely-given informed consent, preferably
in writing. If the consent cannot be obtained in writing,
the non-written consent must be formally documented
||When obtaining informed consent for the research
project the physician should be particularly cautious
if the subject is in a dependent relationship with
the physician or may consent under duress. In that
case the informed consent should be obtained by a well-informed
physician who is not engaged in the investigation and
who is completely independent of this relationship.
||For a research subject who is legally incompetent,
physically or mentally incapable of giving consent
or is a legally incompetent minor, the investigator
must obtain informed consent from the legally authorized
representative in accordance with applicable law. These
groups should not be included in research unless the
research is necessary to promote the health of the
population represented and this research cannot instead
be performed on legally competent persons.
||When a subject deemed legally incompetent, such as
a minor child, is able to give assent to decisions
about participation in research, the investigator must
obtain that assent in addition to the consent of the
legally authorized representative.
|| Research on individuals from whom it is not possible
to obtain consent, including proxy or advance consent,
should be done only if the physical/mental condition
that prevents obtaining informed consent is a necessary
characteristic of the research population. The specific
reasons for involving research subjects with a condition
that renders them unable to give informed consent should
be stated in the experimental protocol for consideration
and approval of the review committee. The protocol
should state that consent to remain in the research
should be obtained as soon as possible from the individual
or a legally authorized surrogate.
|| Both authors and publishers have ethical obligations.
In publication of the results of research, the investigators
are obliged to preserve the accuracy of the results.
Negative as well as positive results should be published
or otherwise publicly available. Sources of funding,
institutional affiliations and any possible conflicts
of interest should be declared in the publication.
Reports of experimentation not in accordance with the
principles laid down in this Declaration should not
be accepted for publication.
C. ADDITIONAL PRINCIPLES FOR MEDICAL RESEARCH COMBINED
WITH MEDICAL CARE
||The physician may combine medical research with medical
care, only to the extent that the research is justified
by its potential prophylactic, diagnostic or therapeutic
value. When medical research is combined with medical
care, additional standards apply to protect the patients
who are research subjects.
|| The benefits, risks, burdens and effectiveness of
a new method should be tested against those of the
best current prophylactic, diagnostic, and therapeutic
methods. This does not exclude the use of placebo,
or no treatment, in studies where no proven prophylactic,
diagnostic or therapeutic method exists. (See footnote*)
||At the conclusion of the study, every patient entered
into the study should be assured of access to the best
proven prophylactic, diagnostic and therapeutic methods
identified by the study.
|| The physician should fully inform the patient which
aspects of the care are related to the research. The
refusal of a patient to participate in a study must
never interfere with the patient-physician relationship.
Note of Clarification on Paragraph 29 of the WMA
Declaration of Helsinki
|The WMA hereby reaffirms its position
that extreme care must be taken in making use of a
placebocontrolled trial and that in general this methodology
should only be used in the absence of existing proven
therapy. However, a placebo-controlled trial may be
ethically acceptable, even if proven therapy is available,
under the following circumstances:
|| Where for compelling and scientifically sound methodological
reasons its use is necessary to determine the efficacy
or safety of a prophylactic, diagnostic or therapeutic
||Where a prophylactic, diagnostic or therapeutic method
is being investigated for a minor condition and the
patients who receive placebo will not be subject to
any additional risk of serious or irreversible harm.
All other provisions of the Declaration of Helsinki must
be adhered to, especially the need for appropriate ethical
and scientific review.