Research Methodology and Biostatistic...Declaration of Helsinki

1. PRESENTED BY
Mr. GANGURDE S.K.
Roll No-06
( M.Pharm-Sem III)
(Pharmacology)
UNDER GUIDANCE
Mrs. WADEKAR J.B.
M.Pharm.
Pharmacognosy
DR.VITHALRAO VIKHE PATIL FOUNDATION’S
COLLEGE OF PHARMACY, VILAD GHAT, AHMEDNAGAR.
2018-19
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2. CONTENTS
1. Introduction: History & Scope.
2. Development of Declaration of Helsinki.
3. Basic Principles of for all Medical Research.
4. Additional Principles for Medical Research combined
with Medical Care.
5. Conclusion.
6. References.
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3. What is Declaration of Helsinki (DoH)?
• A set of ethical principles regarding human
experimentation developed for the medical community by
the World Medical Association (WMA).
• It is widely regarded as the cornerstone document on
human research ethics.
• Followed Nuremberg Code (1947).
• Brazilian forum in 2000 describes- "Even though the Declaration
of Helsinki is the responsibility of the World Medical Association,
the document should be considered the property of all humanity". 3

4. History of DoH
• Adopted in June 1964.
• Has undergone 6 revisions.
• 2 clarifications.
• First significant effort by medical community to
regulate research.
• Prior to Nuremberg Code only specific countries had
National policies (Germany for Example).
• Forms basis of most subsequent documents.
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5. Scope of DoH
• Developed 10 principles first stated in Nuremberg Code.
• Linked to Declaration of Geneva (1948)
• Statement of physicians ethical duties.
• DoH specifically addressed clinical research.
• Relaxed need for IC which Nuremberg code deemed
‘absolutely essential’.
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6. Development of Declaration of Helsinki.
• First Revision 1975.
• Second Revision 1983.
• Third Revision 1989.
• Fourth Revision 1996.
• Fifth Revision 2000.
• Clarifications of Articles 29 & 30 2002 & 2004.
• Sixth Revision 2008.
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7. Development of DoH
• 18th WMA General Assembly, Helsinki, Finland, June 1964.
1. 29th WMA – Tokya, Japan, Oct-1975.
2. 35th WMA – Venice, Italy, Oct-1983.
3. 41st WMA – Hong Kong, Sep-1989
4. 48th WMA – Somerset West, RSA, Oct-1996.
5. 52nd WMA – Edinburgh, Scotland, Oct-2000.
6. 59th WMA – Seoul, Oct-2008.
• Clarifications of Articles 29 & 30 in 2002 & 2004, 53rd & 55th
WMA General Assembly.
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8. First Revision 1975
• 11 years after first adoption of DoH.
• Introduced concept of oversight by Independent committee led to
development of Institutional Review Board (IRB) or Research Ethics
Committee or Ethical Review Board (REC/ERC).
• Issues relating to IC developed – more prescriptive
• Duty to individual given greater weight over duty to society
• Ideas of publication ethics introduced
• Comparison of trial treatment to best available treatment
• Access to treatment following trial completion
• Mandatory for protocols to state they adhered to the DoH
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9. Second & Third Revisions 1983 & 1989
• Fairly minor revisions.
• Consent of minors.
• Further development – Independent committees.
• CIOMS & WHO published International Ethical Guidelines for
Biomedical Research Involving Human Subjects Developed in 1982
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10. Fourth Revision 1996
• The AIDS Clinical Trials Group (ACTG) Study 076 of
100 Zidovudine in maternal-infant transmission of HIV had been
published in 1994.
• This was a placebo controlled trial which showed a reduction of
nearly 70% in the risk of transmission, and Zidovudine became a de
facto standard of care.
• Subsequent HIV studies - US patient had unrestricted access to
AZT while those in developing countries did not that is randomized
to placebo controlled arms.
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11. Continue…
• Justification was provided by a 1994 WHO group in Geneva
which concluded "Placebo-controlled trials offer the best option
for a rapid and scientifically valid assessment of alternative
antiretroviral drug regimens to prevent transmission of HIV".
• These trials appeared to be in direct conflict with recently
published guidelines for international research by CIOMS,
which stated "The ethical standards applied should be no less
exacting than they would be in the case of research carried out
in country“.
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12. Consequence of Fourth Revision
• FDA ignored this revision – continued to refer to 1989
version
• EU cited fourth revision in Clinical Trial Directive of
2001
• Adopted into UK national law in 2004
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13. Fifth Revision 2000
• Extensive revision to structure of document.
• Extensive debate, symposia & conferences.
• No reference to research where there is no potential
benefit to participants.
• Article 29 – placebo controlled studies.
• Article 30 – After care of trial participants.
• Led to clarification points of 2002 & 2004.
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14. Sixth Revision
• Sixth revision cycle commenced in May 2007.
• This consisted of a call for submissions, completed in
August 2007.
• The terms of reference included only a limited revision
compared to 2000.
• In November 2007 a draft revision was issued for
consultation till February 2008 and led to a workshop in
Helsinki in March.
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15. Continue…
• Followed general review.
• Comparatively Minor Revisions.
• Extensive debate & consultation re: 5th & 6th revisions
led to concerns.
• ? Ethical strength of DoH weakened.
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16. 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.
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17. Basic principles for all medical research (Continue)
• 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. 17

18. Continue…
• 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 subjects must be volunteers and informed
participants in the research project.
• 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. Reports of experimentation not in accordance with the
principles laid down in this Declaration should not be accepted for publication.
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19. 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. 19

20. Continue…
• 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.
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21. Continue…
• In the treatment of a patient, where proven prophylactic,
diagnostic and therapeutic methods do not exist or have been
ineffective, the physician, with informed consent from the patient,
must be free to use unproven or new prophylactic, diagnostic and
therapeutic measures, if in the physician’s judgment it offers hope
of saving life, reestablishing health or alleviating suffering. Where
possible, these measures should be made the object of research,
designed to evaluate their safety and efficacy. In all cases, new
information should be recorded and, where appropriate, published.
The other relevant guidelines of this Declaration should be
followed. 21

22. Conclusion
Is the DoH still relevant for the ethical conduct of
clinical Trials?
• YES.
• Remains morally binding for physicians over and above national/local
laws and/or regulations.
• Less influenced by interested parties than ICH GCP guidelines.
• Provides basis for conduct of CTs and has a focus on protection of
subjects/participants.
• “In medical research involving human subjects, the well being of the
individual research subject must take precedence over all other interests”.
• Upholds Kantian respect for persons and view that individuals should not
be treated simply as a means to an end.
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23. References: -
1. World Medical Association (2013). "Declaration of Helsinki: Ethical
Principles for Medical Research Involving Human
Subjects". JAMA. 310 (20): 2191 2194.doi 10 1001 Jama
2013281053. PMID 24141714.
2. WMA Press Release: WMA revises the Declaration of Helsinki. 9
October 2000Archived 27 September 2006 at the Wayback Machine.
3. Snežana, Bošnjak (2001). "The declaration of Helsinki: The
cornerstone of research ethics". Archive of Oncology. 9 (3): 179-84.
4. Tyebkhan, G (2003). "Declaration of Helsinki: the ethical cornerstone
of human clinical research". Indian Journal of Dermatology,
Venereology and Leprology. 69 (3): 245–7.
5. www.who.int/bulletin/archives/79%284%29373.pdf
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24. 6. WMA - Declaration of Helsinki – 2000 version (including
notes of clarification 2002 & 2004).
7. WMA - Declaration of Helsinki – 2008 version.
8. Human, D. & Fluss, S. (July 2001) “The World Medical
Association’s Declaration of Helsinki: Historical and
Contemporary Perspectives”.
9. The Social Medicine Portal (1st June 2008) “FDA Abandons
Declaration of Helsinki for international clinical trials”.
10. http://www.socialmedicine.org/2008/06/01/ethics (accessed 20
Feb 2009)
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