The Principles of Ethics in

Clinical Trials

The Declaration of Helsinki

Rianto Setiabudy
CSU-FKUI
Jakarta, 11 Feb 2016
Introduction

 Atrocity conducted by Nazi’s doctors

 Code of Nuremberg, 1947
 Over-enthusiasm of investigators:
 The history of intravenous drug administration
 Dr. John Hunter’s research
 Syphilis research in Tuskegee, 1930
 Declaration of Helsinki by The World Medical
Assembly (WMA):
 Helsinki, 1964
 Tokyo, 1965
 Venice, 1983
 Hong Kong, 1989
 Somerset West, 1996
 Edinburgh, 2000
 Seoul, 2008
 Fortaleza, 2013
A. Introduction
1. Decl. of Helsinki (DH): states the ethical
principles for medical research involving
human subjects, including indentifiable
human material and data. The DH should be
read as a whole
2. DH: primarily addressed to physicians, but all
are encouraged to adopt it
3. The duty of the physicians: promote and
safeguard the health of the patients, including
those included in medical research
4. Decl. of Geneve:
 “The health of my patient will be my first
consideration”
 The International Code of Medical Ethics:
 “A physician shall act at the best patient’s
interest when providing medical care”
5. Medical progress is based on research that
ultimately must include study in human
subjects.
6. In medical research involving human
subjects, the well-being of the individual
research subjects take precedence over all
other interests (science or society)
7.The primary purpose of CT: improve
prophylaxis, diagnosis, and therapeutics. Also to
understand causes, development and effects of
diseases
8. In every medical research: risks and burdens
for subjects
9. Medical research: ethical standard → promote
respect for subjects and protect their health and
rights.
Vulnerable subjects → need special protection
10. Investigators must consider the ethical, legal,
and regulatory norms from local and
international standards. The protection by set
forth by DH should not be reduced/eliminated by
any national/international requirement
B. Principles for all
Medical Research
11. Physicians must protect the life, health,
dignity, integrity, right for self-determination,
privacy, and confidentiality of research
subjects
12. CT must conform to scientific principles, be
based on knowledge of scientific literature,
relevant source of information, adequate lab,
and experimental animal. Animal’s welfare
must be respected
13. Cautions  research that harms the
environment
14. In all CTs  research protocol describing
ethical considerations, funding, sponsors,
institutional affiliation, potential conflict of
interest, compensation for research-related
injury, and post-study access
15. Before a study begins, its protocol must
have been approved by an independent EC.
It should consider local/international law,
regulation. The EC has the right to monitor the
ongoing study, the and any protocol change
should be approved first by the EC before the
execution
16. Trials involving human subjects: done only
by competent and qualified persons.
Responsibility: on physician or health care
professional, not research subjects
17. Vulnerable population: can be used only if
the study  provides the health needs of this
population and this population can benefit the
result of the study
18. All medical research should be preceded by
assessment of risk + burdens versus potential
benefit for the subjects and communities
19. Every CT should be registered in publicly
accessible database before recruitment of the
first subject
20. Physician may participate if the risks have
been adequately assessed and can be well
managed.
Study should be stop if:
- the risks are found to outweigh the benefit
- the conclusive proof is obtained
21. A study involving human subjects can
be done only if its importance outweighs
the risk and burdens to the subjects
22. Subject participation must be
voluntary. The final decision should be
from the subject involved.
23. Subject’s privacy and confidentiality
should be protected. Study impact on
physical, mental, and social integrity
should be minimized
24. Informed consent should be obtained in a
proper manner: objectives, procedure,
funding, conflict of interest, risk and burdens,
right to refuse and withdraw, confidentiality.
Non-written consent needs witness
25. Studies using human leftover biological
specimens or data need consent. If this is
impossible/ impractical  prior approval from
EC
26. When asking informed consent from a
subject who is very dependent on the
physician, this must be sought by a qualified
person who is independent of this
relationship
27. For incompetent subjects:
 Consent from legally authorized
representative
 Likelihood benefit for this population
 Minimal risk and minimal burden
28. For incompetent subjects who are deemed
capable of making an independent decision 
obtain consent from the legally authorized
representative + assent from the subjects
involed
29. For unconscious subjects where obtaining
informed consent is impossible and delay is
not allowed  recruit first, but ask consent as
soon as subject’s condition allows or legally
authorized representative is available
30. Publications:
 Authors are responsible for accuracy and
completeness of their reports
 Positive and negative results should be
published or
 Declare source of funding, conflict of interest,
and institutional affiliation
 Report not in accordance to DH should net be
accepted for publication.
C. Additional Principles
for Medical Research
Combined with Medical
Care
31. This combination is justified only if it
provides preventive, diagnostic or
therapeutic value and the participation
will not adversely affect the subject’s
health
32. Risk, benefit, and burdens of a new
intervention must be tested against the
best current proven intervention
The use of placebo is justified if:
 No current proven drug exists
 No risk or serious/irreversible harm,
and scientifically sound reasons exist
33. At the end of study inform the subjects
about:
 Outcome and the benefit of the study
 Post-study access

34. Inform the subject: which aspects of the

care is trial-related.
Subject’s refusal to participate should never
affect the patient-physician relationship
35. Unproven intervention may be used if it offers
hope for saving life, re-establishing health or
alleviating suffering.
New information produced from CTs should be
recorded and published

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