The document outlines ethical considerations in research, emphasizing the importance of protecting human subjects and ensuring informed consent. It covers historical developments in research ethics, key ethical principles, and guidelines established through various codes like the Nuremberg Code and the Declaration of Helsinki. Special attention is given to vulnerable populations, including women, children, and prisoners, stressing the need for fairness and the minimization of risks in research participation.

1. Asst. Prof., Dept. of Medical Ethics
King Fahad Medical City – Faculty of Medicine
King Saud Bin Abdul-Aziz University for Health Sciences
Dr. Ghaiath M. A. Hussein
Professionalism and Ethics Education for Residents
(PEER)
Ethical Issues in
Research

2. Outline
• Introduction
• What is research ethics?
• Historical background: How did research ethics develop?
• Ethical principals of research: What makes research ethical?

3. Outline of presentation
What are the ethical issues in research?
– Benefit/harm analysis
– Vulnerability (Risk-Vulnerability Matrix)
– Informed Consent
– Fairness and equity in research participation
– Privacy and confidentiality
– Conflict of Interests (COI)
– Research ethical review
– Clinical trials
– Special topics in research ethics
Ethical issues after the conduct of research: ethics of results
presentation & publication

4. • What is research?
• Where does research fit in the knowledge Management
Cycle (KMC)
• Where are we in terms of research?
INTRODUCTION

5. What is Research?
 “Research” is defined as an undertaking intended to extend
knowledge through a disciplined inquiry or systematic
investigation.
 A determination that research is the intended purpose of the
undertaking, is key for differentiating activities that require
ethics review by an ethics review and those that do not.
 Systematic methodological scientific approach for basic
facts around a certain problem in order to find solutions
based on these facts.

6. :
www.worldmapper.org

7. Research in Context...the KMC
Generation
Dissemination
SynthesisUtilization
Assessment
Research
Statistics

8. “Good” research: Good Science & Good Ethics
“Good” Evidence: near-top to hierarchy of
Evidence
Evidence-Based Healthcare: Better
practice that is based on best evidence
Better health status
Better Ethics is Better Health

9. What Makes a Good Research?
Good
science
Good Ethics
•Problem selection
•SMART objectives
•Proper methodology
•Proper analysis
•Fair subject selection
•Favorable Risk-Benefit Ratio
•Independent Review
•Informed Consent

10. Criteria of “Good” Science Research
• Systematic: The research developed, implemented and
reported in a systematic manner.
• Methodolic: Adopt & use skillfully the research
methods, materials ,approaches in order to ensure reliability
of the results & findings.
• Scientific: The research should be scientifically sound
through utilizing scientific approaches , tools and
techniques.

11. Criteria for Good Ethics:
What Makes Research Ethical?
1. Social or Scientific Value:
– Improve health and wellbeing
– Increase the knowledge
2. Scientific Validity
– Acceptable methods including analysis techniques to
produce valid data (Test the objectives)

12. Criteria for Good Ethics: Cont.
What Makes Research Ethical?
3. Fair Subject Selection:
– Stigmatized and vulnerable are not targeted
– Rich not favored for the benefit of research
– Clear inclusion and exclusion criteria according to the
objectives.
– Clear Strategies for recruitment
4. Favorable Risk-Benefit Ratio

13. 5. Independent Review:
– Review of the Design, the proposed subject selection
and risk-benefit ratio.
6. Informed Consent
7. Respect for the potential and enrolled subjects:
– Privacy and confidentiality
– Informing about the new discovered risks or benefits
– Informing about the results
– Maintaining the welfare of the subjects.
Criteria for Good Ethics:
What Makes Research Ethical?

14. What’s Research Ethics?
 It is the field of ethics that systematically analyze the ethical
and legal questions raised by research involving human
subjects.
 Its main focus is to ensure that the study participants are
protected and, ultimately,
 that clinical research is conducted in a way that
serves the needs of such participants and of
society as a whole.
It works when and only when it is applied before the
research is conducted

15. HISTORICAL
BACKGROUND
BORN IN SCANDAL… THE EVOLUTION OF RESEARCH
ETHICS
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16. Eighteenth and Nineteenth Century
• James Lind “scurvy study in sailors - Salisbury
• Edward Jenner cowpox vaccine test
• 1897 Giuseppe Sanarelli yellow fever test
1900 Walter Reed established several [first ever]
“safeguards”
• Self-experimentation
• Only adults would be enrolled in research
• Written informed consent
• Reimbursement (inducement)

17. History of Research Ethics
Pre-World War II
• Research standards left up to the discretion of the individual
researcher
World War II
• Experiments conducted on inmates of Nazi concentration camps
• 1945-1949 - Trials in Nuremberg, Germany– physicians convicted
of crimes against humanity

18. Nazi Doctors’ Experimentation

19. International Research Guidelines
Nuremberg Code (1947)
- As a result of WWII Nazi experiments
- First international code in research ethics
• Voluntary consent absolutely essential
(restricting research with infants, children, developmentally
challenged, etc.)
• Risk/Benefit Analysis essential to ethics review
• Scientific Soundness is important to ethics review

20. The Nuremberg Code (1947)
The first provision of the code requires that “the voluntary
informed consent of the human subject is absolutely
essential.” The code provides other details implied by such a
requirement:
• Capacity to consent
• Freedom from coercion
• Comprehension of the risks and benefits involved
• Experiment to be conducted by highest qualified persons
The code on the web: http://ohsr.od.nih.gov/nuremberg.php3
Saudi Commision for Health Specialties

21. The Declaration of Helsinki (DOH)
 The World Medical Association created the Declaration of
Helsinki in 1964 and amended in: Tokyo (1975), Venice (1983),
Hong Kong (1989), South Africa (1996), Edinburgh (2000),
Washington (2002), and Tokyo (2004)
 “The well-being of the subject should take precedence over
the interests of science and society”

22. The Declaration of Helsinki (DOH) Cont.
 Consent should be in writing
 Use caution if participant is in dependent relationship with
researcher
 Limited use of placebo
 Greater access to benefit

23. World Medical Association WMA (1964)
 Respect for Persons – people are not a means to an end;
researchers have duty to protect life, health, privacy and dignity
of research participants
 Standard of care must be best available, even for control group
 Proxy consent and assent for vulnerable populations
Saudi Commision for Health Specialties

24.  More than 400 African-
American men with latent
syphilis were followed for the
natural course of the disease
rather than receiving treatment.
 Continued after penicillin
available
 40 wives infected, 19 children
born with congenital syphilis
TUSKEGEE SYPHILIS STUDY,
ALABAMA ( 1932 – 1972 )

25. Willowbrook Study, New York
1956-1972, NYU
 800 Children Willowbrook
State School for the
Mentally Retarded
 Researchers injected
students with mild form of
hepatitis

26. The Belmont Report (1979)
 In 1972, the public became aware of the Tuskegee study, which took
place in the southern United States from 1932 to 1972.
 In 1974 the National Commission for the Protection of Human Subjects
of Biomedical and Behavioral Research was established.
 In 1978, the commission submitted its report titled, The Belmont
Report: Ethical Principles and Guidelines for the Protection of Human
Subjects of Research.
Those principles respect for persons, beneficence and justice
are accepted as the 3 fundamental principles for the ethical
conduct of research involving human participants.

27. Council for International Organizations
of Medical Science (CIOMS) Guidelines (1993)
• Informed consent
• Research in developing countries
• Protection of vulnerable populations
• Distribution of the burdens and benefits
• Role of ethics committees

28. Is it over?... Torvan trial in Kano, Nigeria
 Kano Trovan clinical trials in 1996, on pediatric age group,
during the worst ever meningococcal meningitis.
 Lack of proper Governmental authorization and informed
consent during the studies publicized in 2000, by
Washington Post.
 Court trial and release of investigation panel reports
stalled in Nigeria.
 Suit for 5.8 billion USD moved to the USA and report
leaked there too.
 Settlement out of court being discussed.

30. Ethical Principles of Research
What makes research ethical?

31. What Makes the Research Ethical?
1- Social or Scientific Value:
• Improve health and wellbeing
• Increase the knowledge
2- Scientific Validity
• Acceptable methods including analysis techniques to produce
• Valid data (Test the objectives)

32. 3- Justice and Inclusiveness:
• Stigmatized and vulnerable are not targeted
• Rich not favored for the benefit of research
• Clear inclusion and exclusion criteria according to the objectives.
• Clear Strategies for recruitment
4- Favorable Risk-Benefit Ratio:
• Identification and Minimization the risk
• Enhancement of the potential benefit
• Risk to the subject are appropriate to the benefits to the
subject and society.
What Makes the Research Ethical? Cont.

33. What Makes the Research Ethical? Cont.
5- Independent Review:
• Review of the Design, the proposed subject
selection and risk-benefit ratio.
6- Free and Informed Consent:
• Provision of Information
• Voluntarily and Consists with the values

34. 7- Respect for the potential and enrolled subjects and Respect
for Vulnerable Persons :
• Right to withdrawal
• Privacy and confidentiality
• Informing about the new discovered risks or benefits
• Maintaining the welfare of the subjects.
What Makes the Research Ethical? Cont.

35. WHAT ARE THE ETHICAL ISSUES IN
RESEARCH?
•Benefit/harm analysis
•Vulnerability (Risk-Vulnerability Matrix)
•Informed Consent
•Fairness and equity in research participation
•Privacy and confidentiality
•Conflict of Interests (COI)

36. Benefits
• Benefits to research subjects
• Benefits to society
• Specific new, effective intervention
• Knowledge which some time in the future may
lead to effective interventions

37. Benefits to Research Subjects
Direct Benefit
– Arising from the intervention being studied
– Information that can influence care, e.g., diagnostic
Collateral “indirect” Benefit
– Arising from being a subject, even if one does not receive the
experimental intervention
– Extra supervision from being in the research study (?)
– Access to medical care not available for economic reasons
– Unplanned or unanticipated benefits

38. Benefits to Research Subjects
 Inspirational
 Aspirational
• Benefit to society (arises from the results of the study)
 Payments or incentives – benefits?
Any level of research risk could be offset by such gains if
they were significant enough

39. Benefits to Research Subjects
No benefits from the research
– Phase I trials testing maximum tolerated dose
– Non-therapeutic research procedures
• Mechanism of disease

40. Risk/Harm
• Risk:
– Means any harm or injury that affect the subject or the
participant under study.
• Risk:
– “ A state of uncertainty where some of the possibilities
involve a loss, catastrophe, or other undesirable outcome. ”

41. Types of risks
Physical risks:
1. Cold: Nazi Experiments with ice tanks
2. Pressure: Nazi experiments in high altitude
3. Heat: Heat stroke; Burn; Exhaustion
4. Noise: High noise may lead to impairment or loss of hearing
5. Light: Dim light may affect the vision

42. Nazi Experiments

43. High Altitude Experiments

44. Types of Risk…Cont.
Medical Risks:
1. Therapeutics: (Tuskegee expirement)
2. Preventive: (Trials of polio vaccine)
3. Diagnostic:
• Irradiation:
- Teratogenic effect to the fetus.
- Carcinogenic effect.
• Samplings:
- Biopsies: tissues that contain genetic information about
the participant.
- Surgical hazards.
- Too risky procedures (under anesthesia)

45. The Forgotten Risks
 Social Risks:
Stigma (e.g. research on HIV-AIDS, STDs).
 Emotional Risks:
On families when their children were chosen for trial of
new vaccine; research in war.
 Psychological Risks:
Questionnaires with sensitive questions to participants
in sensitive positions, as to ask poor people about there
nutrition and houses.

46. Risk to the Society
 Manipulating environmental factors (Pathogenic organisms and
toxic chemicals).
 Economic risk
 Legal risks:
Vulnerable groups, e.g., prisoners, children, pregnant women.

47. Categorization of Risk
Risk is categorized by severity into:
1. Minimal Risk: As routine blood sample , throat swabs, vaginal
swabs, sputum exams
2. Above Minimal Risk: That can be minimized, and within the
toleration of the participant.
3. Too Risky: The most dangerous type, and the Researcher
should not be allowed to conduct a research that endangers
the life of the participants e.g. live cancer cells , live virus

48. Minimal Risk
The probability and magnitude of harm or discomfort
anticipated in the research are not greater in and of
themselves than those ordinarily encountered in daily
life or during routine performance of physical or
psychological examination or tests

49. Clinical Equipoise
• Clinical equipoise means a genuine uncertainty on the
part of the expert medical community about the
comparative therapeutic merits of each arm of a clinical
trial.
• The tenet of clinical equipoise provides a clear moral
foundation to the requirement that the health care of
subjects not be disadvantaged by research participants.

50. Minimization of Risk
 Adequate facilities ,procedures and personnel for dealing with
emergencies .
 Arrangement made for monitoring and detecting adverse out
comes .
 All trials should be reviewed by a Data Safety Monitoring Board
(DSMB).
 All potential toxins, mutagens or teratogens used should be
justified.
 The National Committee for Atomic Energy should complete
risk assessment for the use of the radiation and radioactive
substances .

51. Minimization of Risk
For Drugs:
- Registration, its trade name, chemical name and
pharmacological class .
- Recommended dose, form of administration in the study.
- Known or possible interaction with other drugs, side effects and
adverse reactions.
- Placebo should be justified.

52. Minimization of Risk
Social Risks:
- The research should have potential to enhance the future
health of the society .
For vulnerable groups :
- Additional safeguards needed to protect there rights and
welfare .
For recruitment materials:
- (posters, newspapers, T.V, videos ……).
Should be acceptable if submitted.

53. Minimization of Risk
For Psychological Risks :
• Sensitive questions for sensitive group like those with
AID, STDs, T.B, can be questioned through 3rd person or ask the
help of
psychologists .
Economic Risks :
• Traveling cost can be solved out.
• Absentees issues should also be solved out.

54. Minimization of Risk
Legal :
- The risk should be reasonable in relation to the anticipated
benefits to the subjects or society.
- Privacy of subject should be adequately protected.
- For tissue samples containing genetics information the subject
should have option to withdraw at any time.

55. Vulnerability
(Risk-Vulnerability Matrix)
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56. Definition
 Vulnerable: “Vulnerable persons are those who are relatively (or
absolutely) incapable of
 protecting their own interests. More formally, they may have I
insufficient power, intelligence, education, resources strength,
or other needed attributes to protect their own interests.”
(CIOMS, 2002)
Saudi Commision for Health Specialties

57. Who is Vulnerable?
Making use of this definition… let’s
brainstorm!
www.amanet-trust.org

58. Who is Vulnerable?
1. WOMEN
 Women in the reproductory age group are usually excluded in
drug/vaccine studies where the possible effects on fetus are
not known.
 As justice to women, their health conditions should be
addressed through involving them in research.
 Types of research that benefit women directly include,
obstetrics and gynecology, sexually transmitted infections,
vitamin studies etc.

59. Who is Vulnerable?
2. PREGNANT WOMEN
 Should be awarded special protection because of additional
health concerns during pregnancy and the risk of damage to
the fetus.
 Pregnant women must be excluded from research unless the
purpose is to meet the health needs of the mother, and
 The fetus will be placed at risk only to the minimum extent
necessary to meet such needs or
 The risk to the fetus is minimal

60. Who is Vulnerable?
3. CHILDREN
 Particularly vulnerable group. The major ethical issue for
involving children is that parents are the primary decisions
makers for their minor children.
 There must be no undue inducement to participate for parent,
guardian or child, although reimbursement of expenses is
allowed.
 A “small gift” to the child after completion of the research is
however acceptable.

61. Requirements for involving
in Research
 The purpose of the research is to obtain knowledge relevant to
the health needs of children
 A parent or legal representative of each child should give
permission;
 The agreement (assent) of each child has been obtained to the
extent of the child`s capabilities; and
 A child`s refusal to participate or continue in the research
should be respected.

62. Assessment of Risk in children
 Minimal Risk- risk in relation to normal experience of
average, healthy normal children – daily life/routine physical
psychological exams
 Minimal Risk varies with age but not social status, illness or
circumstances
 Consultation with experts – pediatricians , social workers etc

63. Who is Vulnerable?
4. MENTALLY ILL / MENTALLY HANDICAPPED PERSONS
 Is he/she capable of self-determination?
 Respect for the immature and the incapacitated may require
protecting them as they mature or while they are incapacitated
(Belmont Report)
 It is usually that informed consent will be provided by a
surrogate/ legal representative of that person.
 The golden rule for involving mentally ill or handicapped people
is that ; The objections of these subjects to involvement should
be honored, unless the research entails pro-providing them a
therapy unavailable elsewhere.

64. Who is Vulnerable?
5. THE ELDERLY
 Old age alone does not render a person incapable of
consenting to health research.
 In the absence of any indication to the contrary, elderly
patients are generally assumed to be competent to
consent to research.
 However, consideration should be given to the possibility
of mental deterioration, the ability to comprehend, and
the dependence and vulnerability of the elderly

65. Who is Vulnerable?
6. PRISONERS
 Prisons are organizational structures exacerbate vulnerability of
the incarcerated individuals.
 They have limited economic power, inadequate protection of
human rights, limited availability of health care and treatment
options.
 The prison structure makes the incarcerated prisoners confined,
stressed, crowded, psychologically devastated with symptoms
such as psychosis, severe depression, and complete social
withdrawal.

66. Who is Vulnerable?
7. CAPTIVE/DISPLACED/RETURNING POPULATIONS
 Have constrained movements and choices
 Refugees, those in police custody, and displaced population,
 Hospitalized patients, students, institutionalized persons and
military personnel.
 Readily available for research activities for extended periods,
enhancing their attractiveness to research enterprise.
 Researchers should always have to be sure if participant’s
decision making capacity is not compromised.

67. How to Decide?
 Nature and degree of risk
 The condition of the particular population involved and,
 The nature and level of the anticipated benefits.
 Relevant risks and benefits must be thoroughly arrayed in
documents and procedures used in the informed consent
process

68. Assessment of Risk-Vulnerability
Research Risk depends on both Level of Invasiveness
(physical, psychological or emotional) and Vulnerability of
participants.
Vulnerability is generally a pre-existing condition, in that it
exists regardless of whether the research is conducted or not.
It can be inherent or situational.

69. Tri-Council Policy Statement
Ethics Review (Cont.)
Invasiveness: consider the physical, psychological,
emotional and legal harms that could be caused by
or exacerbated by the research.
Group Invasiveness
Vulnerability Low Medium High
Low Exp. Exp. Full
Medium Exp. Full Full
High Full Full Full

70. Risk/Vulnerability Matrix

71. Conclusion
 Vulnerability is considered to offer better protection, not to stop
research on the vulnerable
 Vulnerable groups should not be denied their right to
participate in relevant research
 The risk assessment varies with the degree of vulnerability

72. Informed Consent

73. Definition
 “Autonomous authorization of a medical intervention…by
individual patients/participants“
(Beauchamp and Faden, 2004)
 It's the practical expression of patient's autonomy, and the
respect for him/her personality

74. Components of FIC:
1. "Disclosure" refers to the provision of relevant
information by the clinician and its comprehension by
the patient.
2. "Capacity" refers to the patient's ability to understand
the relevant information and to appreciate those
consequences of his or her decision that might
reasonably be foreseen.
3. "Voluntariness" refers to the patient's right to come to
a decision freely, without force, coercion or
manipulation.

75. Disclosure
VoluntarinessCapacity

76. 1. Disclosure
This refers to the process during which physicians
provide information about the proposed research to
the participant.

77. Eight Required Elements
[45 CFR 46.116(a) & 21 CFR 50.25]
1. Statement that study in research and information on
purposes / duration / procedures / experimental procedures
2. Reasonably foreseeable risks or discomforts
3. Reasonably expected benefits
4. Alternative procedures

78. Eight Required Elements Cont.
[45 CFR 46.116(a) & 21 CFR 50.25]
5. How confidentiality will be maintained
6. Information on compensation for injuries (unless minimal risk)
7. Contact persons for information on research, injury, subject’s
rights
8. Voluntary participation, no penalty or loss of benefits for
refusal or withdrawal

79. Six Additional Elements
1. Statement that there may be risks which are unforeseeable
2. Under what circumstances investigator could terminate
subject’s participation
3. Additional costs to subjects
4. Consequences of subject’s withdrawal from research
5. Statement that will be told of new findings
6. Approximate number of subjects in study

80. Forms of Consent
Normally, should be provided by participants themselves.
• Deferred consent: is where the subject is entered into a research
study and consent is gained from surrogates after a specified
period of time for continuation of the subject’s inclusion in the
trial.
• Prospective informed consent : represents an attempt to canvass
support in advance from a population considered at risk of
developing a serious illness.
• Surrogate consent (SDM): ideally a substituted judgment made by a
person responsible for health care decision-making for a particular
patient under the relevant legislation

81. Waiver of Informed Consent
REC must find and document that the following criteria
have been satisfied:
 Poses no more than Minimal risk research
 Waiver or alteration will not adversely affect the rights and
welfare of the subjects
 Research could not practicably be carried out without the waiver
or alteration
 Does not involve a therapeutic intervention
 Subjects will be provided with additional pertinent information
All of the above must apply

82. Documentation of Informed Consent
 Written consent document
 Language understandable to the subject or the subject’s Legally
Authorized Representative (LAR)
 Signed by subject or subject’s LAR
 Copy SHALL be given to subject
 Opportunity to read before signing

83. Principles for Providing Information
the Participant:
 Make it clear; avoid jargon
 Use language appropriate to the patient's level of understanding
in a language of their fluency
 Pause and observe patients for their reactions
 Invite questions from the patient and check for understanding

84. Principles for Providing Information
the Participant: Cont.
 Invite the patient to share fears, concerns, hopes and
expectations
 Watch for patients' emotional response: verbal and non-verbal
 Show empathy and compassion
 Summarize the imparted information
 Provide contact information (and other resources)

85. 2. Capacity:
Refers to the presence of a group/set of functional abilities a person
needs to possess in order to make a specific decisions
(Griso and Applebaum, 1998).
These include:
 To UNDERSTAND the relevant information
 To APPRECIATE the relatively foreseeable consequences of the
various available options available.

86. 3. Voluntariness:
• Refers to a participant’s right to make participation decisions
free of any undue influence.
Influences include:
• Physical restraint or sedation
• Coercion involves the use of explicit or implicit threat to
ensure that the treatment is accepted
• Manipulation involves the deliberate distortion or omission of
information in an attempt to induce the subject’s
participation

87. Voluntariness
• Free of undue influence
• Persuasion: appeals to reason
• Manipulation
• Coercision: explicit or implicit threats
• Force: restraint or sedation

88. MANIPULATION
• Distortion of facts or omission
• Non-coercive alternation of choices
• Undue financial payment
• Undue influence, government funding only at
grade eight for hpv

89. Practical Challenges to a "Fully Informed
Consent"
• Diagnostic uncertainty
• Complexity of medical information
• Linguistic and cultural differences
• Overworked health personnel
• Paternalistic approach in doctor-patient
relationship in developing countries, including
Sudan.

90. Informed Consent from Children
• Written Parental/Guardian consent only
required for those below the “legal age”
• Assumption : best interests of the child should
be regarded
• Both parents of the child should sign or just
one?
• Institutionalised children?
• Children without any recognisable legal
guardian?

91. Assent
After the age of seven and below legal
consenting age (which is different for different
countries depending on regulations) those
who are competent to understand the opinion
of the child should be respected
“A child’s affirmative agreement to participate
in research. Mere failure to object should not
be construed as assent” Silence Assent

92. Assent
Waiver of parental consent may be granted in
adolescent research in certain circumstances
i.e. drug abuse, sexual behaviour etc.
Assent documents may include – age
appropriate information sheets and forms
where applicable

93. PRIVACY AND CONFIDENTIALITY

94. Privacy
The right to be left alone and to keep
personal information inaccessible to
others (the condition of limited access to
a person)
Saudi Commision for Health Specialties

95. Privacy
 Relates primarily to Process of clinical examination
and collecting data
Often Challenging in Natural Environment
Can inconvenience research participants
Can encounter participants in public
Procedures and processes can compromise privacy
Some institutions and cultures not accustomed to privacy,
or do not value it

96. Infringements of privacy
• Infringements is justified under
certain circumstances; if:
1. Necessary for research conduct
2. Doesn’t create harm to participants
3. There is societal benefit

97. Confidentiality
- The duty to respect the research participant’s confidence that
the researcher/doctor will not disclose the information he/she
received as part of research of health care.
- How someone will deal with the information that was
disclosed to him in confidence
- Failure to keep private information is an infringements
of confidentiality
- Deliberate
- Accidental

98. Measures to respect confidentiality
• Avoid identifiable data
• Encode the collected data
• Limit access to data
• Keep in password-protected PC
• Destroy the original copies after analysis, or
publication
• Training of research team on confidentiality
• Release information without identification
To each of the previous conditions, there
are ethically-acceptable exceptions

99. Breaking Confidentiality
• Court order
• Communicable diseases
• Vulnerable person abuse/neglect
• Driving/flying/machine safety
• Dangerous patients

100. Unanticipated Problems: Examples
• STDs research – placement of clinic. Sign on door.
• Waiting with others, who knows you?

101. Important Considerations:
• Retention of data after the study is complete
• Secondary uses and linkage of data (i.e.
databases)
• How much personal information is actually
necessary for the study?

102. CONFLICTS OF INTEREST (COI)

103. What is an interest?
• An interest may be defined as a commitment, goal,
or value held by an individual or an institution.
• Examples include a research project to be
completed, gaining status through promotion or
recognition, and protecting the environment.
Interests are pursued in the setting of social
interactions.

104. What is COI?
• COI exists when two or more contradictory interests relate to
an activity by an individual or an institution.
• Conflicts of interest are “situations in which financial or other
personal considerations may compromise, or have the
appearance of compromising, an investigator’s judgement in
conducting or reporting research.” AAMC, 1990

105. What is COI? Cont.
• “A conflict of interest in research exists when the individual
has interests in the outcome of the research that may lead to
a personal advantage and that might therefore, in actuality or
appearance compromise the integrity of the research.”
NAS, Integrity in Scientific Research

106. Levels of COI
• Researchers
• The REB should assess the likelihood that the
researcher’s judgment may be influenced, or appear
to be influenced, by private or personal
interests, and assess the seriousness of any harm
that is likely to result from such influence or from the
mere appearance of undue influence (TCPS, 200)

107. Levels of COI
Conflicts of Interest by REB Members
• It is of the highest importance that members of the
REB avoid real or apparent conflicts of interest .
• For example: when their own research projects are
under review by their REB or
• when they have been in direct academic conflict or
collaboration with the researcher whose proposal is
under review.

108. Levels of COI
Institutional Conflicts of Interest
• Situations may arise where the parent organization has a
strong interest in seeing a project approved before all
ethical questions are resolved.
• The REB must act independently from the parent
organization.
• Institutions must respect the autonomy of the REB and
ensure that the REB has the appropriate financial and
administrative independence to fulfill its primary duties.

109. What comprises COI?
• Stock ownership
• Paid employment Board membership
• Patent applications (pending or actual)
• Research grants (from whatever source)
• Travel grants and honoraria for speaking or participation
at meetings

110. What comprises COI? Cont.
• Gifts Membership of lobbying organizations
• Relationship with the National Research Ethics Review
Committee, or with possible reviewers of the paper
• Relationship with organizations and funding bodies
Membership of a government advisory board

111. Is it always bad?
COIs may result in:
1. Loss of objectivity
2. Reordering of priorities towards applied research
3. Degradation of the nature of science as an open
and collegial enterprise
4. Exploitation of trainees
5. Transfer of time and interest to Commercial
ventures

112. • In May 2004, the pharmaceutical giant Pfizer agreed
to pay $430 million to settle a lawsuit by a former
employee turned whistle-blower, who was joined in
the lawsuit by the U.S. federal government and 11
state governments.
• The lawsuit exposes various marketing practices by
the company Warner-Lambert – later bought by
Pfizer.

113. • Leading academic researchers were paid
to deliver promotional lectures at
educational events and to publish
favorable reports on the off-label use of
its epilepsy drug, Neurontonin.
L. Kowalczyk “Pfizer Drug Strategy Probed: States Question Marketing Tactics for
Neurontin,” Boston Globe, October 18, 2002,
Saudi Commision for Health Specialties

114. Conflicts Can Occur at all Levels of
Research
• In reviews/awarding of grant
• In ethics review of grant
• In recruitment of participants
• In analysis of data
• In presentation of data

115. The Case of Nancy Oliveiri
• In 1996, Olivieri found that the drug she was
researching (deferiprone, active iron-chelating agent )
at the Hospital for Sick Children in Toronto was showing
unexpected potential risks to some patients in the
trials.
• The drug company sponsoring her research abruptly
terminated the trials and issued warnings of legal
action against Olivieri should she inform her patients at
the Hospital for Sick Children of the risks, or publish her
findings.

116. The Case of Nancy Oliveiri Cont.
• The manufacturer (Apotex) issued more legal
warnings to deter Dr Olivieri from communicating
this second unexpected risk of L1 to anyone.
• However, she published her findings in the New
England Journal of Medicine and

117. The Case of Nancy Oliveiri Cont.
• She was subsequently dismissed from her position as
Director of the Hospital for Sick Children Program of
Hemoglobinopathies.
• Apotex was planning to donate USD 100 Million to
the University of Toronto

118. The Case of Nancy Oliveiri
• After more than seven years of legal battle, an
independent committee of inquiry into the matter
vindicated Olivieri and concluded that neither the
university nor the hospital offered her appropriate
support in her conflict with the drug company.
• Olivieri was reinstated to her position at the Hospital
for Sick Children and her actions have also been
vindicated by several other independent reports.

119. The other side of the story
• Deferiprone is the only effective orally active iron-
chelating agent licensed for the treatment of
patients with thalassaemia major and other
disorders of transfusional iron overload.
• It is the only alternative to deferoxamine—a drug
that has to be given by daily subcutaneous infusions
and fails in many patients worldwide because of the
lack of compliance, high cost, toxicity, or
hypersensitivity.

120. The other side of the story
• No other clinicians using the drug had found
evidence for long-term liver damage and her
interpretation of the data was immediately
questioned in letters to the New England Journal of
Medicine.
• Four of her patients in whom liver fibrosis had been
suggested also had hepatitis C and all five had iron
overload—both causes of liver fibrosis.

121. LET’S DEBATE…!
What do you think?
OR ?

122. Practical Steps to resolve
• Disclosure / transparency
• Stringent analysis of COI,
• Review of contracts between funders and
researchers
• Close external monitoring
• Blinding of study, when possible
• Restrict review of colleague’s work
• Peer review of manuscripts

123. ETHICAL REVIEW OF RESEARCH

124. What is Ethical Review?
• It is a process by which research proposals are
reviewed for their compliance and accordance
with the national/international ethical
principles & guidelines for research involving
human subjects.

125. Research Requiring Ethics Review
All research involving living human subjects by
collecting identifiable information or materials
including:
 Research with human remains, cadavers, tissues,
biological fluids, embryos and fetuses.
 Interviews, surveys and questionnaires.
 Secondary data analysis of data from living human
subjects.

126. Research exempt from Ethics Review:
 Research about living individuals in the public arena or
artists, based exclusively on publicly available
information.
 Participant observation of public demonstrations,
political rallies and public meetings.
 Quality assurance studies, performance reviews or
normal educational testing.

127. DISCUSSION…
Q & A