15-Nov-17

History and Principles of

Research Ethics
Temidayo O Ogundiran
MBBS (Ibadan), MHSc (Toronto), FACS, FRCS (Edinburgh),
FWACS

Division of Oncology, Department of Surgery, University of Ibadan and University College Hospital, Ibadan
West African Bioethics Programme, University of Ibadan

Outline
• Ethics
• Research Ethics
• History of Research Ethics
• Fundamental Issues in Research Ethics

1
 15-Nov-17

Acquisition of
knowledge
research

Transmission of
Application of
knowledge
knowledge
dissemination public service

Competence of the Researcher

• Academic and professional competence

• Scientific validity

• Ethical issues- participant’ protection issues, scientific rigour and

thoroughness, etc

2
 15-Nov-17

ETHICS

What is Ethics?

• Ethics is the systematic study of morality

• The relationship between ethics and morality is

similar to that between logic and thinking or that
between theology and religion

3
 15-Nov-17

Aim

Ethics aims to achieve two fundamental objectives:

• To tell us how we ought to act in a given situation

• To provide us with strong reasons for doing so

Ethics and Morality

Ethics and morality are closely related:
• ‘Morality’ refers to a set of duties that require us to
subordinate our natural instincts in order to obey
the moral law. A failure to fulfill our duty brings with
it a heavy sense of guilt

• Very often, morality is assumed to have a religious

basis – an assumption that is not always correct

4
 15-Nov-17

Branches of Ethics
i. Normative ethics, also known as prescriptive ethics.
This branch of ethics actually judges morality
Normative judgments are value judgments: they indicate
whether something is good or bad.
Example: To proclaim that:
Abortion is right or wrong
Advanced directive is good or bad
Euthanasia is morally good or bad, etc.

Branches of Ethics
ii. Meta-ethics
This is the branch of ethics that concerns itself with
the analysis or elucidation of ethical concepts or
ideas.
Example: What do the terms “good,” “bad,” “right,”
“wrong,” “evil,” “moral obligation,” etc. signify?
How may we define a good action?

Meta-ethics is also known as analytic moral

philosophy

5
 15-Nov-17

Branches of Ethics
iii. Applied ethics
The attempt to apply ethical theory to real life situations.
The discipline has many specialized fields.
Examples: Engineering Ethics, Bioethics and Business
ethics

It involves the investigation of specific questions that have

elicited ethical controversies, such as end of life issues, in
vitro fertilization, environmental degradation, world
poverty, how to deal with conflicts arising from our multi-
cultural world, etc.

Branches of Bioethics
• Research Ethics
• Medical Ethics
• Clinical Ethics
• Bioethics education
• Organizational Ethics
• Public Health Ethics
• Environmental Ethics
• Genomics and Genetics Ethics
• Animal Ethics
• ETC.

6
 15-Nov-17

Ethics
‘should’

Policy Law
‘usually’ ‘must’

13

Which Ethics?
• Personal Ethics: how each of us lives our lives
• Professional Ethics:
-standards we pursue in our working environment and
organisation
-professional protocols and standards
• Ethics of our Profession: what we must do to meet our societal
obligations

7
 15-Nov-17

Application of Ethics to Professional

Activities
• Rules e.g. Kantian, Consequentialist, etc.

• Principles: autonomy, beneficence, non-maleficence, justice

• Ideals e.g. virtue (Aristotelian): intellectual, moral (benevolence,

fairness, generosity, honesty, loyalty, patience, tolerance, etc.)

RESEARCH ETHICS

8
 15-Nov-17

Research Ethics
• A subset of applied ethics (bioethics) and is concerned with
responsible conduct of biomedical research in conformity with
standard norms and practices
• These norms were written partly in response to unpleasant events in
the history of biomedical research
• These norms have developed into codes /guidelines that are now
widely accepted and applicable in many national and international
jurisdictions

RESEARCH ETHICS

The analysis of ethical issues that are raised when people are
involved as participants in research

18

9
 15-Nov-17

Research Ethics
Objectives
• Protection of human participants
• Conduct of research in a way that serves
interests of individuals, groups and/or
society as a whole
• Examining specific research activities and
projects for ethical soundness, protection
of confidentiality and the informed
consent process

19

Research Ethics
• The goal of all medical research is to improve human well being
But:
• How can the rights of individual persons be reconciled with the
demands of the scientific enterprise?
• Can such a laudable collective goal be pursued with full
protection of the rights and dignity of individuals?

10
 15-Nov-17

HISTORY OF RESEARCH ETHICS

Research Ethics
• Though medical research has succeeded in increasing the
well-being of much of the world, the successes were not
without costs

• Many studies violated the rights and dignity of participants

and, in some cases, cost them their health or even their
lives

11
 15-Nov-17

1ST CENTURY EXPERIENCE

• Celsius, a 1st century Roman historian wrote about
research. Celsius justified experiments on condemned
criminals on the following grounds:

• “It is not cruel to inflict on a few criminals sufferings which

may benefit multitudes of innocent people through all
centuries”

• This reflects an imbalance between the two goals of

research: that of medical progress and the protection of
the rights and welfare of human subjects

• In the type of case cited above, a concern for medical

progress is made to override the concern for human
welfare and protection

Pre- World War Experimentation

• 1897- Italian bacteriologist Guiseppe Sanarelli isolated Yellow fever
organism and inoculated 5 persons with his isolate to prove his claim

• 1900- Walter Reed experimented the cause of yellow fever among

the Yellow Fever Board by self experimentation. Jesse Lazear, a
member died in the experiment. Consent was obtained and $100 paid
to willing undertakers, another $100 to those who became ill due to
the disease

12
 15-Nov-17

Pre- World War Experimentation...

• Max Bockhart inoculated a patient suffering with paralysis with a pure
culture of gonococus- the patient died ten days later

• Ernst Bumm introduced a pure culture of gonococcus to the urethra

of 2 healthy woman who subsequently developed painful gonococcal
urethritis

Pre- World War Experimentation...

Many other cases of gonococcal inoculation occurred:
• Four paralytic patients
• A woman suffering from malignant VVF
• 14 hopeless patients with consumptives
• Eyes of infants
• 6 blind adults inoculated with muco-purulent discharge of pregnant
parturient women

13
 15-Nov-17

Pre- World War Experimentation...

• William Wallace, a Dublin Physician in 1830s inoculated five healthy
individuals , 19-35 years of age with syphilis
• Inoculation continued thereafter towards the end of that century
• In 1875, R Voss inoculated three prostitutes aged 13-16 years with
the milk of a syphilitic patient

Pre- World War Experimentation...

• 1887 Eugene Hahn of Berlin removed a portion of a woman’s breast
cancer and transplanted it into the healthy one
• 1887 Dr Stickler inoculated children with the blood of horses and
cows and later inoculated them with blood from scarlet fever
patients
• Roberts Bartholow of Ohio conducted series of galvanic irritation of
the exposed cerebrum of a woman with cancer of the skull skin

14
 15-Nov-17

Nazi German war experimentation

Thousands of concentration camp prisoners were
subjected to brutal and inhuman experiments:
• High altitude (low pressure) experiments
• Freezing experiments
• Malarial experiments
• Mustard gas experiments
• Sulfanilamide experiments
• Typhus experiments
• Poison experiments
• Human twin studies
• Incendiary bomb experiments
• Sterilization experiments

The formal codification of ethical guidelines for the conduct of

research involving humans began in the late 1940s.

In 1946, 23 Nazi defendants, twenty

of them physicians, were tried for
war crimes and crimes against
humanity. 16 of the defendants
were found guilty. 7 were hanged
and 9 were sentenced to prison
terms ranging from ten years to life.

The world was shocked at the revelations of experiments

these doctors conducted, including studying the effects of
extreme cold, high altitude, exposure to noxious substances,
poisons, infection with all manner of disease, and a terrible list
of other procedures.

15
 15-Nov-17

Out of this experience grew a set of

principles known as the Nuremberg Code,
which have remained remarkably durable.
Although they were intended to apply
primarily to medical research, they serve
as useful guidelines for the conduct of
other types of research, including
research typically conducted by
behavioral and social science
investigators

The 1932-72 Tuskegee Syphilis Study

• The research project was conducted by the U.S. Public Health Service

• 600 low-income African-American males, 400 of whom were infected

with syphilis, were monitored for 40 years

• Free medical examinations were given; however, subjects were not

told about their disease

• Even though a proven cure (penicillin) became available in the 1950s,

the study continued until 1972 with participants being denied
treatment

16
 15-Nov-17

The 1932-72 Tuskegee Syphilis Study...

• In some cases, when subjects were diagnosed as having syphilis by other
physicians, researchers intervened to prevent treatment

• Many subjects died of syphilis during the study

• The study was stopped in 1973 by the U.S. Department of Health, Education, and
Welfare only after its existence was publicized and it became a political
embarrassment

• In 1997, under mounting pressure, President Clinton apologized to the study

subjects and their families

Japanese Medical Scientists

• Cruel medical experiments with a biological warfare research corps
unit 731, conducted during the war
• Received immunity from post war prosecution in exchange for
exclusive American access to the results of the experiments

17
 15-Nov-17

And many others......

• 1959 Thalidomide tragedy and Congressional requirement for patient
consent
• 1963 Brooklyn Jewish Chronic Disease Hospital experiment with live
cancer cells on elderly patients without their consents
• Willowbrook study of deliberate exposure of children and youths to
hepatitis
• Henry Beecher’s 22 study expose

1996: The Pfizer Trovan Study (1)

• There was an early 1996 CSM epidemic in Kano, Nigeria

• It attracted humanitarian workers, e.g. Medicine San Frontiers (MSF)

a.k.a. (Doctors without Boarder”)

• More than 15,000 people died during the epidemic

18
 15-Nov-17

1996: Pfizer’s Trovan Study (2)

• Pfizer’s “participation in the control” left a raging
controversy yet unresolved

• The trial was to validate the safety and efficacy of

Trovafloxacin (Trovan) in treating Meningococcal
meningitis

• The U. S. and Nigerian medical teams from Pfizer

and Johns Hopkins Medical School in Baltimore,
U.S.A. came together

• They administered Trovan to about 100 children,

randomized from a population where the MSF
workers were treating patients with proven and
approved drugs for the disease

1996: The Pfizer Trovan Study (3)

• The experimental group received Trovan

• An equal number received low dosage of

Ceftriaxone, an accepted drug for meningitis
(control group) as adequate dose

• 11 of the 100 children in the exp group died

• Others developed brain damage leading to partial

paralysis or deafness

19
 15-Nov-17

1996: The Pfizer Trovan Study (4)

• No ethical approval was obtained from (ERC) (whether
national, state or local).

• Subjects were not informed about the risks of the drug

• In August 2001, 30 families from northern Nigeria

instituted a suit in New York

• They alleged the trial violated:

1. The Nuremberg Code
2. The Declaration of Helsinki
3. Article 7 of the International Covenant on Civil and
Political Rights
4. FDA regulations and other norms of international law

Scandals fed Regulations

• Nuremberg Code 1949
• World Medical Associations Declaration of Helsinki 1964
• CIOMS
• National Research Act and the Belmont Report 1974/79
• The Council for International Organizations of Medical Sciences (CIOMS)
guidelines entitled International Ethical Guidelines for Biomedical Research
Involving Human Subjects (1993/2002)
• ICH-GCP Guidelines 1996
• Nigerian National Code of Health Research Ethics 2007
• And lots more..............

20
 15-Nov-17

Biomedical Research
• The primary intent of research is knowledge production
• Biomedical research involves human beings who are exposed to risks
• A thin line exists between therapy and research
• The quest for knowledge should not override human welfare

Biomedical Research...
• The judgment was left solely in the hands of researchers, guided by
their own conscience and the advice and oversight of their peers
• Leaving decisions solely to investigators and participants was not
adequate to avoid unjustifiable research taking place (History of
Research Ethics)
• Managing the conflict between scientific and protective goals is REC’s
mandate

21
 15-Nov-17

Issues in Research Ethics

• Human research participants protection issues
• Regulatory issues in research
• Informed consent
• Risks, exploitation, compensation, inducement and the tandard of Care
• Independent review of research protocols
• Responsible conduct of research and research misconduct
• Data acquisition, storage and management
• Conflicts of interest
• Publication, authorship and the peer review process
• ETC

Key Players of Human Research Protection

Programme
• Institutional officials
• REC – Chair, Members, Administrator
• Investigators
• Research Staff
• Others within organisation (e.g.data monitors, research paticipants and their
families)
• Others outside organisation (e.g. sponsor, regulatory agency, Ministry of
Health, etc)

22
 15-Nov-17

Research Ethics Committees

• Institutional Review Boards (IRBs)
• Research Ethics Committees (RECs)
• Ethics Review Committees (ERCs)
• Ethical Review Committee (ERC)- Ghana
• Health Research Ethics Committees (HRECs)- Nigeria

Essential Roles and Functions of REC

• Protection of research participants and communities
• Protection of researchers from running foul of regulations; and from
undue pressures from collaborators, institutions and sponsors
• Pursuance of institutional missions and goals
• Preservation of integrity in the overall scientific enterprise
• Preservation of public trust in science and scientific discoveries

23
 15-Nov-17

Carrying Out These Roles

• Education
• Policy and Procedures
• Protocol Review
• Conduct of Study, Monitoring or Oversight
• Prevention/detection of scientific fraud
• Programme Assessment

Review Continuum

Exempt Expedited Full

(administrator/chair) (chair/IRB member/admin) (full IRB)

Low Minimal Higher

RISK

48

24
 15-Nov-17

Ethics Review is not a barrier to research

What Makes Research Ethical?

• Social value
• Scientific validity
• Fair subjects selection
• Favourable risk-benefit ratio
• Independent review
• Informed consent
• Respect for potential and enrolled subjects
• Collaborative partnership

25
 15-Nov-17

Resources and Further Readings

• Agulanna C. Moral Theories. West African Bioethics 2009
• Michael Pollanen: The Ethical Pathologist. Joint Centre for Bioethics,
University of Toronto
• Burnett L, McQueen MJ, Jonsson JJ, Torricelli F et al. IFCC Position
Paper: Report of the IFCC Taskforce on Ethics: Introduction and
frameworkClin Chem Lab Med 2007;45(8):1098–1104
• Martin McKneally. What is Ethics? University of Toronto, 2003

Resources and Further Readings

• Michael D. Mann, The ethics of collecting and processing data and publishing
results of scientific research. Available at:
http://www.unmc.edu/ethics/data/data_int.htm
• Online research ethics course. Available at
http://ori.dhhs.gov/education/products/montana_round1/issues.html
• Sara Rockwell. Ethics of Peer Review: A Guide for Manuscript Reviewers
• Elizabeth Heitman, Ruth E. Bulger. Assessing the educational literature in the
responsible conduct of research for core content. Accountability in Research,
12:207–224, DOI: 10.1080/08989620500217420

52

26
 15-Nov-17

Resources and Further Readings

• Shamoo A and Resnik D. 2009. Responsible Conduct of Research,
2nd ed. (New York: Oxford University Press).
• Council for International Organizations of Medical Sciences (CIOMS)
Guidelines
• Institute of Medicine-National Research Council, 2002:Integrity in
scientific research-creating an environment that promotes
responsible conduct
• Malcolm R Parks and Mary L Disis. Conflicts of interest in
translational research. Journal of Translational Medicine 2004, 2:28
doi:10.1186/1479-5876-2-28

Resources and Further Readings

• Schneider B and Schuklenk U. Scientific misconduct. Developing World
Bioethics 2005; 5(1);92-108
• Institute of Medicine-National Research Council, 2002:Integrity in scientific
research-creating an environment that promotes responsible conduct
• ORI Introduction to the responsible conduct of research
• Francis L Macrine. Scientific integrity, 2005: 3rd edition
• IF Adewole. Research Integrity. West African Bioethics Program, 2005
• Anderson MS, Steneck NH. The problem of plagiarism. Urologic Oncology:
Seminars and Original Investigations 29 (2011) 90–94

54

27
 15-Nov-17

Resources and Further Readings

Ezekiel E et al. What makes research ethical.

The Nuremberg Code
WMA Declaration of Helsinki
CIOMS Guidelines

55

Resources
• Widdows H, Dickenson D, Hellsten S. Global bioethics New Review of Bioethics
2003;1(1):101-116
• McKneally M. What is an ethic? University of Toronto
• Scandals and tragedies of research with human participants
• Schüklenk U. Introduction to research ethics. Developing World Bioethics 2005;
5(1):1471-8847 (online)
• IF Adewole. Research Integrity. West African Bioethics Program, 2005
• Christopher O. Agulanna. History of Research Ethics, West African Bioethics
Program, 2009

28
 15-Nov-17

Resources...
• The human radiation experiments: Final report of the president’s
advisory committee, Oxford UP 1996, 74-109
• J. Katz. Experimentation without restriction. In Experimentation with
human beings 1972
• Nancy Walton. What is research ethics?
http://www.researchethics.ca/what-is-research-ethics.htm

29