History of ethical guidelines to clinical trial

1. HISTORY OF ETHICAL GUIDELINES
IN CLINICAL TRIAL
Presented by
Anjusha ut
M.Pharm 1st
year
Pharmacy practice
Gov.Medical college calicut

2. What is Ethics?
 The word 'ethics' is derived from the Greek word,
ethos, which means custom or character.
 Ethics is the systematic study of values, so as to
decide what is right and what is wrong.

3. Ethics of Clinical Research
 Ethical requirements in clinical research :
 Minimize the possibility of exploitation;
 Ensure that the rights and welfare of subjects are
respected

4. History
 Nuremberg Code, 1947
 Kefauver Amendmens 1962 (thalidomide)
 Declaration of Helsinki, 1964 → 2013
 Belmont Report 1979
 ICH GCP guidelines, 1996
 Ethical Guidelines for Biomedical Research in Human
Subjects (ICMR), 2000

5.  During 2nd
world war - American military
tribunal opened criminal proceedings against
23 leading German Nazi physicians for
crimes against humanity.
 German Physicians conducted medical
experiments on thousands of camp prisoners
without their consent.
 Most of the participants of these experiments
died or permanently crippled.
Nuremberg Trail 1947

6. Nuremberg Code
 The Nuremberg Code is a set of research
ethics principles set as a result of Nuremberg
Trials.
 The ten points of the Nuremberg Code
"the voluntary consent of the human subject
is absolutely essential"

7. NUREMBERG CODE
1) The voluntary consent of the human subject is absolutely essential.
2) The experiment should be such as to yield fruitful results for the good of
society.
3) The experiment should be designed and based on the results of animal
experimentation and a knowledge of the natural history of the disease.
4) The experiment should be so conducted as to avoid all unnecessary physical
and mental suffering.
5) No experiment should be conducted where there is a prior reason to believe
that death or disabling injury will occur; except, 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.
8) The experiment should be conducted only by qualified persons.
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, If necessary the scientist in charge
must be prepared to terminate the experiment at any stage.

8. Kefauver Amendments 1962
 In 1962 the world was once
again shocked by the severe
foetal limb deformities linked to
the use of maternal thalidomide.
 In fact this drug reaction was
only discovered after 10,000
infant were born on over 20
countries world wide.

9.  In response to this the kefauver amendment were
passed - For the first time, drug manufacturers were
required to prove to the FDA the effectiveness of
their products before marketing them.

10. The Declaration of Helsinki 1964-2013
 The willowbrook state study (to know natural course of
infective hepatitis in children) & Jewish Chronic Disease
Hospital study (to understands body’s ability to reject cancer cells
in debilitated subjects) were examples of unethical
research.
 This led the World Medical Association to develop
Declaration of Helsinki.
 The Declaration of Helsinki augmented the
principles set forth by the Nuremberg Code.

11.  This Declaration has undergone 7 revisions (recent in oct 2013).
 A notable change from the Nuremberg Code was a relaxation of the
conditions of consent…… obtain consent “if at all possible”. and
research was allowed without consent where a proxy consent such
as a legal guardian was available.

12.  Introduced the concept of oversight by an
'independent committee’Or Ethics committees
 “All protocols must be submitted to an ethics
committee for review, which must be independent of
the investigator, the sponsor or any other kind of
undue influence”.

13. Belmont Report 1979
 In US ethical guidelines setup after the discovery of
Tuskegee Syphilis Study.
 Based on this unethical study National Commission
for the Protection of Human Subjects of Biomedical
& Behavioral Research was formed which wrote the
Belmont report.

14.  It summarizes ethical principles & guidelines for
research involving human subjects.
 Three core principles are
Respect for persons
Beneficence
Justice

15.  ICH is the International Conference
on Harmonisation of Technical
Requirements for Registration of
Pharmaceuticals for Human Use.
 Good Clinical Practice (ICH-GCP)
Is an international quality standard
provided by ICH
ICH-GCP 1996

16. GCP
 "A standard for the design, conduct, performance,
monitoring, auditing, recording, analysis, and
reporting of Clinical Trials that provides the
assurance that the data and reported results are
credible and accurate, and that the rights, integrity,
and confidentiality of trial subjects are protected"
ICH E6 1.24

17.  The first very important event contributed for the
introduction of GCP is declaration of helsinki. Is widely
regarded as corner stone document of human
research ethics.

18. WHO-GCP VS ICH-GCP
DIFFERENCES
 The WHO started the process of developing
guidelines in the late 1960, by the mid 1970 one of
their scientific group formulated to propose the
guidelines for research in the field of drug
development.
 Which eventually concluded with WHO-GCP
guidelines published in 1995. These reports provide
the basis for ICH-GCP as an international guideline
published in 1996.

19. The 13 Principles Of GCP
1) Clinical trail should be conducted in accordance with
the ethical principles in the declaration of helsinki &
that are consistent with the GCP.
2) Anticipated benefits justify the risks.
3) The rights , safety & well-being of the trial subjects
are the most important considerations & prevail over
the interests of science & society.

20. 4) Adequate non-clinical & clinical information.
5) Scientifically sound, and clearly described ,
detailed protocol.
6) Proposed trail must comply with the protocol
approved by the IEC.
7)Medical care/ decisions- responsibility of qualified
person.

21. 8) Each individual should be qualified by education,
training & experience.
9) Freely given informed consent form obtained from
every subject prior to trial participation.
10) Data handling to allow accurate reporting.
11) Privacy & confidentiality should be protected.
12) Ips- in accordance with GMP.
13) Procedures that assure quality should be
implemented.

22. Ethical Guidelines for Biomedical
Research on human subjects 2000
 ICMR in 1980, released a policy statement on ethical
considerations involved in research on human
subjects.
 This was the first statement giving official guidelines
for establishment of Ethics committees(ECs) in all
Medical colleges & Research centers.
 In 1970s & 1980s researchers at the Institute for
Cytology & Oncology in New Delhi, carried out a
study on 1158 women patients of different stages of
precancerous lesions of the cervix.

23.  These patients were left untreated, to see how
many lesion progressed to cancer & how many
regressed.
 After the controversy , the study became public in
1997, the ICMR started developing Ethical
Guidelines for Biomedical research on human
subjects & finished them in the year 2000.
 These are a set of guidelines which every
researcher in India should follow while conducting
research on human subjects.

24. References
 Ethics in clinical research: the indian perspective-
Indian journal of pharmaceutical sciences 2011 Mar-
Apr.
 Principles and practice of clinical trail medicine by
Richard chin. Bruce Y lee

25. THANK YOU