RESEARCH ETHICS

1. Violation of research ethics: History of violations of research ethics date back to 1930’s

• 1932 Tuskegee syphilis study conducted by the US public health services ( 1932-1972) in which patients were not told they had Syphillis. Treatment for Syphilis was available but withheld. The purpose of the study was to observe the natural progress of the disease. Patients were deceived, coerced and treated unjustly,

• 1939-1945 In Nuremberg Germancy Nazi Germancy physicians had carried out

experiments in camp prisonens like Injecting them with viruses, forcing them to swallow poison ,exposing prisoners to extreme temperature etc.

The physicians were tried for committing atrocities against humanity. In 1948 the Nuremberg military tribunal sentenced “seven” of them to death.

• 1950 the Willow brook hepatitis study in the US in which mentally retarded children were deliberately infected with hepatitis virus, parents were coerced to enter the study. Consent from parents was not obtained

• 1960 Liver cancer cells were injected into 22 senile patients at New York City’s Jewish hospital without consent

• 1962 The Thalidomide disaster in which the drug was used in the US to treat symptoms associated with pregnancy. Pregnant patients were not told that the drug was still in experimental stage. Extensive use resulted in “Phocomelia” in the offsprings

• 1970 Tea room study in which scientists in one center in the US conducted a study on homosexuals behaviour without their consent and published the results without confidentiality

• 1970 San Antonio ( USA ) contraception study in which scientists conducted a clinical trial on new oral contraception by randomizing participants into two arms, placebo and the test. Women were not informed of this randomization as expected, there was a high number of unplanned pregnancies in the “ placebo” arm

• 1999- death of an 18 year old man participating in gene therapy without proper consent.

• April 2000 the American society of Gene therapy made it clear that financial conflicts were involved in this study

2003- The trial of Thomas Butler, an infectious disease scientist who lost plague samples from Tanzania. He also collected the samples from patients without proper consent . He was sentenced to jail and in Texas for illegal shipping of plague

II: History of the Evolution of Ethical Principles in Clinical Research

• The history of the development of formal ethical principles of research in humans can be traced to Word war II between 1939 – 945. The atrocities committed by the Nazi physicians led to the formulation of the first International Code ( A set of rules or principles for regulating conduct of research involving humans ).The first of these codes was:

-The Nuremberg Code ( 1948).

- Declaration of Helsinki 1964, was endorsed by the world medical Association ( WMA). The declaration has been revised (1975,1983,1996,2000)

• The Belmont report written in 1979

- Established 3 ethical principles and

guidelines for conducting research involving humans : These included:

• Respect for persons

• Beneficence

• Justice

• These principle dictate to researchers that “we do not have the right to use people for scientific benefit without their permission, no matter how noble the cause may seem”

- International Ethical Guidelines for biomedical research involving human subjects were also formulated by the Council for International Organizations of medical Sciences ( C I O M S), Geneva,

- In addition , many countries including developing ones have formulated country specific guidelines on ethics of biomedical research taking into account countries unique socio-cultural, political, economic , religious and moral factors

- Another development was the formulation of guidelines in 1986 and 1990 by the London Royal College of Physicians on research involving patients.

- The fundamental principle in all the guidelines is the value placed on human life and the protection of the rights and welfare of all human subjects who participate in scientific experimentation.

The table 1 below is a list of some international guidelines.

Year Organization Title of guideline1) 1947 War crimes tribunal Nuremberg

at Nuremberg Code

2) 1948 UN General Universal declaration Assembly of human rights

3) 1964 World Medical Declaration of Helsinki Association (WMA) (I) .

4) 1975 W M A Declaration of Helsinki (2), Tokyo

5) 1983 W M A Declaration of Helsinki (3) ,Venice

6) 1989 W M A Declaration of Helsinki (4) Hong kong

7) 1991 CIOMS/ WHO International Guidelines for Ethical

Review of Epidemiolo gical studies

8) 993 CIOMS/ WHO International Ethical Guidelines for Biomedical Research involving human

subjects

9) 1995 WHO Guidelines for Good clinical Practice for

trials on Pharmaceutical products

10) 1996 W M A Declaration of Helsinkii(5) south Africa

11) 1996 W M A Declaration of Helsinki (5) South Africa

12) 1997 Council of Europe Convention for the protection of Human

being with regard t0the application and medicine

13) 1997 UNESCO Universal declaration on the human genome and human rights

14) 2000 European Union Charter of fundamental rights of the European Union

15) 2000 UNAIDS Ethical considerations in HIV preventive vaccine Research

16) 2000 WHO Operational Guidelines for Ethics Committees that review biomedical research

biomedical research 17) 2000 WMA Declaration of Helsinki ( 6),

Edinburgh

18) 2001 European parliament Relating to the implementation

of G C P in the conduct of

Clinical trials on medicinal

products for human use

GCP=Good clinical practice

The Declaration of Helsinki

• Established a set of basic principles form which were derived same general rules of conduct

• The current revision ( 2000) places more emphasis for using human subjects in research aimed at improving:

• diagnosis • therapeutics • prophylaxis

• According to the current version ( 2000) of the declaration the following issues are over emphasized:

- any research carried out involving human participants must be based upon scientific principles

- and according to a properly formulated protocol

- and approved by a research ethics committee

-The declaration also reinforces the importance of informed consent

-The declaration adds a provision that allows for informed consent to be provided by a legal guardian for people unable to provide consent for themselves (individuals with diminished autonomy) eg. children, mentally retarded individuals etc

III. Fundamental Principles of Research Ethics.

• In 1974 a National Commission for the protection of human subjects for Biomedical and Behavioural Research was established in the USA

• The work of the above commission was documented in the Belmont report in 1978/1979 (Belmont is a city in the USA)

Fundamental Principles of Research Ethics---------

• The Belmont report was titled “Ethical Principles and Guidelines for protection of human subjects”

• The Belmont report presented 3 ethical principles that guide the work of modem researchers these are:

-Respect for persons-Beneficience-Justice

Respect for persons

-This means that informed consent process is needed so that potential participants are given all the information they need to desire participating in the study or not.

-The principle of respect for persons also means that researchers conducting research on “vulnerable “ population eg. children mentally retarded person prisoners etc) should ensure that protecting them against exploitation.

Respect for persons----

- Coercion ( undue influence Vs Voluntary) Basically means forcing someone to do something that is not good for him/her eg. Use of money to convince volunteers to participate in research may be unethical

Informed Consent

-Participants must be competent to voluntarily give informed consent

-If voluntary informed consent is not possible as in vulnerable subjects like children and mentally retarded people, surrogate but legally acknowledged decision makers should give consent

Respect for persons----

-Privacy and confidentiality sensitive information collected for research purposes must be protected.

- Access to this information must be limited to a well defined group eg. Researchers and Institutional Review Board ( IRB)

2) The 2nd principle of Research ethics is Beneficence.

Beneficience-------

- A need to ensure that all aspects of the study must be designed in a way to maximize benefits and minimize risks to participants

- Under this principle , a risk/ benefit analysis may need to be performed on every proposed study to determine if this ratio is ethical

Justice

3) Justice

-Refers to the fairness involved in the selection of research participants

-This is to ensure that risks or benefits incurred by research participants are not unfairly concentrated in one segment of the population

Important reference

1) The Ethics of Research related to health in developing countries

Published by Nuffield Council of Bioethics April 2002

Website: http: // www . Nuffieldbioethics.org

2) Clinical Research . What it is and how it works 2004 by Jones and Bartlett Publishers,Inc

References-----

3) Hand book for Clinical investigation by Carola Lemme 2nd Edition 2003

Copyright: Carola Lemme and Student litteratur 2003

Web : www . Studentlitteratur .sc