ETHICS IN RESEARCH

SREERAJ S R

Sreeraj S R
WHY IS RESEARCH ETHICS IMPORTANT?

It ensures a common standard to;

 respect for those who ‘take part’ in research,
 ensures reasonable, safe and thoughtful demands by
researchers and
 ensures sufficient knowledge is shared by all concerned.

Green R. Research Ethics: A guide to principles and

procedures. 
Sreeraj S R
HISTORY

Sreeraj S R
 TUSKEGEE EXPERIMENT
ON SYPHILIS, 1932 – 72

 Even though a
proven cure
(penicillin) became
available in the
1950s, the study
continued until 1972
with participants
being denied
treatment!
 In 1997, Clinton
apologized to the
study subjects and
their families.

https://alondranelson.wordpress.com/2012/07/25/tuskegee-and-the-black- Sreeraj S R
panther-party/
 NAZI EXPERIMENTS,
1939 – 45

JOSEF MENGELE (1939-

45)..”THE ANGEL OF DEATH”
• The experiments resulted in
death, disfigurement or
permanent disability,
• Considered as examples of
medical torture

http://rosario1960.blogspot.in/2012/11/the-diaries-of-nazi-war-crimi Sreeraj S R
nal-josef.html
 HUMAN RADIATION EXPERIMENTS BY U.S. GOVERNMENT,
1944–74

Experiments including:
 Feeding radioactive material to
mentally disabled children
 Enlisting doctors to administer
radioactive iron to impoverished
pregnant women
 Exposing U.S. Soldiers and prisoners to
high levels of radiation
 Irradiating the testicles of prisoners,
which caused severe birth defects
 Exhuming bodies from graveyards Human
without the consent of the families for
radiation tests. experimentation
ttps://en.wikipedia.org/wiki/Human_radiation_experiments
in the name ofSreeraj S R
 JEWISH CHRONIC
DISEASE HOSPITAL
STUDY - 1963
 Dr. Southam’s research
purpose was to see if the
immune systems of
chronically ill people
would react any
differently to cancer
compared to the immune
systems of healthy
people. 
 The patients were
injected with live cancer
cells and lied to them
that they were being
injected with human cells
that were growing in test
tubes. 

https://raceandhealth.weebly.com/1963-jewish-chornic-disease-h
ospital-study
Sreeraj S R
 WILLOWBROOK HEPATITIS
STUDIES, 1956 - 70

 Mentally retarded children

housed at the Willowbrook
State School in Staten Island,
New York, were intentionally
given hepatitis to track the
development of the viral
infection.

http://www.qcc.cuny.edu/SocialSciences/ppecorino/MEDICAL_ETHICS
_TEXT/Chapter_7_Human_Experimentation/Case_Study_Willowbrook Sreeraj S R
_Experiments.htm
 PFIZER STUDY IN NORTHERN NIGERIA, 1996

During an epidemic of meningococcal meningitis in Kano, Nigeria,

Pfizer tested new antibiotic, trovafloxacin in100 children against100
receiving the gold-standard anti-meningitis treatment, ceftriaxone.
Allegations;
• participants and their families were not told that they were part of a trial.
• Pfizer gave the children a substantially low dose of existing treatment,
ceftriaxone (33mg/kg) instead of recommended 50 – 100 mg/kg.
• did not obtain official approval before testing a new drug.
• Manipulating the documents by backdating an approval letter a year
after the study had taken place.
https://en.wikipedia.org/wiki/Abdullahi_v._Pfizer,_Inc.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1119465/ Sreeraj S R
MILESTONES IN ETHICAL DEVELOPMENT

Sreeraj S R
 MILESTONES IN ETHICAL DEVELOPMENT

• Nuremberg Code (1947).

• W.M.A’s Declaration of Helsinki (1964).
• Belmont Report (USA) (1979)-Tuskegee syphilis study
• Council for International Organizations of Medical Sciences
(CIOMS) 1993.
• International Conference on Harmonization of Technical
Requirements for Registration of Pharmaceuticals for
Human Use (ICH), in 1996, Guideline on Good Clinical
Practice,E6 (GCP).
Sreeraj S R
 NUREMBERG CODE- 1947

The Nuremberg Code drafted at the end of the Doctor’s trial in

Nuremberg 1947 has been hailed as a landmark document in medical
and research ethics. 
It has served as a foundation for ethical clinical research since its
publication 70 years ago. 
Its principles emphasize;
• a profound respect for the voluntary nature of research participation,
• the idea of true informed consent, and
• the personal ethical responsibilities of the investigator to ensure
human welfare.
Ghooi RB. The Nuremberg Code–A critique. Perspect Clin Res. 2011 Apr-Jun; 2(2): 72–76.
doi: 10.4103/2229-3485.80371
Sreeraj S R
 THE TEN POINTS OF THE NUREMBERG CODE

1. Required voluntary, well-informed, consent of the human subject.

2. The experiment should aim at positive results for society that cannot be procured in
some other way.
3. It should be based on previous knowledge (e.g., from animal experiments).
4. Avoids unnecessary physical and mental suffering and injuries.
5. The experiment should not cause a risk of death or disabling injury.
6. Risks should never exceed the benefits.
7. Adequate facilities should be used to protect subjects.
8. Conducted only by qualified scientists.
9. Subject should always be at liberty to stop at any time.
10.Scientist must terminate the experiment if continuation would be dangerous.
https://en.wikipedia.org/wiki/Nuremberg_Code
http://www.nejm.org/doi/full/10.1056/NEJM199711133372006 Sreeraj S R
 THE BELMONT REPORT: 1979

• First written by the National Commission for the Protection of

Human Services of Biomedical and Behavioral Research, United
States. 
• Prompted in part by problems arising from the Tuskegee Syphilis
Study (1932–1972).
• The three fundamental ethical principles for using any human
subjects for research are:
1. Respect for persons
2. Beneficence
3. Justice
https://en.wikipedia.org/wiki/Belmont_Report
Sreeraj S R
 BELMONT REPORT – PRINCIPLES 1. RESPECT FOR
PERSONS

1. Respect for persons: How?

• Informed Consent
• Individuals should be
treated as autonomous • The consent process must
agents include three elements:
• Information,
• Persons with diminished • Comprehension, and
autonomy must be • Voluntary participation
protected from coercion by •Researchers must be truthful and
others and from activities
conduct no deception
that harm them.
https://en.wikipedia.org/wiki/Belmont_Report
http://www.rss.hku.hk/HREC/BelmontReport.rtf.
Sreeraj S R
 BELMONT REPORT – PRINCIPLES II. BENEFICENCE

• Based on Hippocratic How?

philosophy of “Do no • Assessment of risks and
harm” benefits
• Human participants should • The nature and scope of
not be harmed risks and benefits must be
• Research should maximize assessed in a systematic
possible benefits and way
minimize possible risks
https://en.wikipedia.org/wiki/Belmont_Report
http://www.rss.hku.hk/HREC/BelmontReport.rtf.
Sreeraj S R
 BELMONT REPORT – PRINCIPLES III. JUSTICE

The benefits and risks of How?

research must be distributed • Ensuring reasonable, non-
fairly. exploitative, and well-
considered procedures which
are administered fairly
• the fair distribution of costs
and benefits
to potential research
participants
https://en.wikipedia.org/wiki/Belmont_Report
http://www.rss.hku.hk/HREC/BelmontReport.rtf. Sreeraj S R
 DECLARATION OF HELSINKI: 1964

• DoH is a set of ethical principles for human

experimentation developed by the World Medical
Association (WMA).
• Adapted from Nuremberg Code.
• Originally adopted in June 1964 in Helsinki, Finland.
• Undergone seven revisions, most recent in October 2013. 
• Growing considerably in length from 11 paragraphs in 1964
to 37 in the 2013 version.
https://en.wikipedia.org/wiki/Declaration_of_Helsinki

Sreeraj S R
DOH 2013

DECLARATION OF HELSINKI (2013).pdf

Sreeraj S R
 COUNCIL FOR INTERNATIONAL ORGANIZATIONS OF MEDICAL
SCIENCES (CIOMS)
• The Council for International Organizations of Medical
Sciences (CIOMS) is an international, non-governmental,
non-profit organization established jointly by WHO and
UNESCO in 1949.
• CIOMS mission is to advance public health through
guidance on health research including ethics, medical
product development and safety.

https://cioms.ch/about/ Sreeraj S R
 INTERESTING FACTS ABOUT CIOMS

• The General Assembly of UN adopted CIOMS Principles of

Medical Ethics Related to Prisoners in 1983.
• The World Health Assembly adopted CIOMS Ethical Criteria
for Medicinal Drug Promotion in 1974.
• CIOMS pharmacovigilance guidelines have been the basis
for respective ICH guidelines.

https://cioms.ch/about/ Sreeraj S R
RESEARCH ETHICS: THE INDIAN PERSPECTIVE

Sreeraj S R
 BACKGROUND

In 1970s and 1980s researchers at the Institute for Cytology

and Preventive Oncology, New Delhi, carried out a study on
1158 women patients of different stages of cervical dysplasia
who were left untreated to see how many lesions progressed
to cancer and how many regressed. By the end of the study;
• 71 women had developed malignancies and
• lesions in 9 of them had progressed to invasive cancer.
• 62 women were treated only after they developed localised
cancer.
Sanmukhani J, Tripathi CB. Ethics in Clinical Research: The Indian Perspective. Indian Journal of Pharmaceutical Sciences. 2011;73(2):125-130. Sreeraj S R
 ICMR GUIDELINES

 The Indian Council of Medical Research (ICMR)

started developing ‘Ethical Guidelines for
Biomedical Research on Human Subjects’ and
finalized them in the year 2000.
 These are a set of guidelines which every
researcher in India should follow while
conducting research on human subjects.
 These guidelines have been put into force
through Schedule Y: Clinical Trial Regulation In
India.
 The guidelines were revised in 2017. 

Sanmukhani J, Tripathi CB. Ethics in Clinical Research: The Indian Perspective. Indian Journal of Pharmaceutical Sciences. 2011;73(2):125-130. Sreeraj S R
 SCHEDULE Y

• Schedule Y, came into existence in 1988 under Drugs and

Cosmetic Act 1945.
• Enforced by Central Drugs Standard Control Organization
(CDSCO) in India.
• Schedule Y for India is a law and not a mere guideline.

Nair L. Summary Of Schedule Y. https://wwwslidesharenet/lekshmilnair/summary-of-schedule-y.

2011.
Sreeraj S R
GENERAL PRINCIPLES OF ICMR ETHICAL GUIDELINES

Principle of

1. Essentiality 7. Professional competence

2. Voluntariness 8. Maximization of benefit
3. Non-exploitation 9. Institutional arrangements
4. Social responsibility 10.Transparency and
accountability
5. Ensuring privacy and
confidentiality 11.Totality of responsibility

6. Risk minimization 12.Environmental protection

Sreeraj S R
ICMR General Principles.pdf

Sreeraj S R
CTRI

The Clinical Trials Registry- India (CTRI), hosted at the ICMR's

National Institute of Medical Statistics (http://nims-icmr.nic.in
), is a free and online public record system for registration of
clinical trials being conducted in India that was launched on
20th July 2007 (www.ctri.nic.in).

Sreeraj S R
 REFERENCES

1. Sanmukhani J, Tripathi CB. Ethics in Clinical Research: The Indian Perspective. Indian Journal of Pharmaceutical Sciences. 2011;73(2):125-130.
2. Green R. Research Ethics: A guide to principles and procedures. Available at:
https://wwwstaffsacuk/images/researchethicsadinov05_tcm68-21512ppt. Accessed March 15, 2018.
3. https://alondranelson.wordpress.com/2012/07/25/tuskegee-and-the-black-panther-party/
4. http://rosario1960.blogspot.in/2012/11/the-diaries-of-nazi-war-criminal-josef.html
5. https://en.wikipedia.org/wiki/Human_radiation_experiments
6. https://raceandhealth.weebly.com/1963-jewish-chornic-disease-hospital-study
7. http://www.qcc.cuny.edu/SocialSciences/ppecorino/MEDICAL_ETHICS_TEXT/Chapter_7_Human_Experimentation/Case_Study_Willowbrook_Expe
riments.htm

8. https://en.wikipedia.org/wiki/Abdullahi_v._Pfizer,_Inc.
9. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1119465/
10.Ghooi RB. The Nuremberg Code–A critique. Perspect Clin Res. 2011 Apr-Jun; 2(2): 72–76. doi: 10.4103/2229-3485.80371
11.https://en.wikipedia.org/wiki/Nuremberg_Code
12.http://www.nejm.org/doi/full/10.1056/NEJM199711133372006
13.https://en.wikipedia.org/wiki/Belmont_Report
14.Basic Principles of the Belmont Report.  http://www.rss.hku.hk/HREC/BelmontReport.rtf.
15. https://en.wikipedia.org/wiki/Declaration_of_Helsinki
16. Nair L. Summary Of Schedule Y. https://wwwslidesharenet/lekshmilnair/summary-of-schedule-y. 2011.

Sreeraj S R