HISTORY OF ETHICAL GUIDELINES IN CLINICAL TRIAL

Presented by Anjusha ut M.Pharm 1st year Pharmacy practice Gov.Medical college calicut

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.

Ethics of Clinical Research Ethical requirements in clinical research :

Minimize the possibility of exploitation; Ensure that the rights and welfare of subjects are

respected

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

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

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"

NUREMBERG CODE1) 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.

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.

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.

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.

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.

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”.

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.

It summarizes ethical principles & guidelines for research involving human subjects.

Three core principles are Respect for persons Beneficence Justice

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

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

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.

WHO-GCP VS ICH-GCPDIFFERENCES

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.

The 13 Principles Of GCP1) 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.

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.

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.

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.

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.

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

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