A lecture presented by Dr. Ghaiath Hussein in University of Khartoum for the students of the MSc programme in Genetics/Molecular Biology. Session 1 (Introduction): Definition of ethics, bioethics and medical ethics. What is an ethical issue? International approaches to medical ethics Islamic approaches to medical ethics

1. PRESENTED FOR UNIVERSITY OF KHARTOUM
MSC PROGRAMME IN GENETICS/MOLECULAR
BIOLOGY
30/04/2014
Presented by:
Ghaiath Hussein, MBBS, MHSc. (Bioethics)
Doctoral Researcher, Uni. Of Birmingham, UK
ghaiathme@gmail.com

2. Outline of today’s session
 Introduction: Research and Knowledge Management
Cycle (KMC)
 Historical background of research ethics
 What makes research ethical?
 Examples of ethical issues in biotechnological and
molecular research
 How to proceed with our research ethically?

3. What is Research?
 “Research” is defined as an undertaking intended to
extend knowledge through a disciplined inquiry or
systematic investigation.
 Systematic methodological scientific approach for basic
facts around a certain problem in order to find solutions
based on these facts.
Research on Humans:
The systematic undertaking of activities that involve the
collection of human personal data, measurements, and/or
biological samples for purposes that are not related to
clinical management of a health condition

4. ‫السكان‬ ‫من‬ ‫مليون‬ ‫لكل‬ ‫المنشورة‬ ‫العلمية‬ ‫المقاالت‬ ‫عدد‬ ‫يوضح‬ ‫وجدول‬ ،‫المنشورة‬ ‫العلمية‬ ‫المقاالت‬ ‫عدد‬ ‫حيث‬ ‫من‬ ‫العالم‬ ‫دول‬ ‫حجم‬ ‫توضح‬ ‫خريطة‬‫لعا‬‫م‬2001‫م‬.‫المصدر‬ :
www.worldmapper.org

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

6. “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

7. 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

8. 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.

9. Criteria for Good Ethics:
What Makes Research Ethical?
1. Social or Scientific Value
2. Scientific Validity
3. Fair Subject Selection
4. Favorable Risk-Benefit Ratio
5. Independent Review
6. Informed Consent
7. Respect for the potential and enrolled
subjects

10. 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

12. 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

13. Year Benchmark
2013 WMA updates DOH (Brazil)
2010 TCPS updated
2008 WMA updates DOH (Seoul)
2004 WMA updates DOH (Tokyo)
2002 WMA updates DOH (Washington) CIOMS Guidelines updated
2000 WMA updates DOH (Edinburgh)
1998 Tri-Council Policy Statement (TCPS)published in Canada
1996 WMA updates DOH (South Africa)
1993 CIOMS guidelines for biomedical research involving human subjects
1991 US CFR title 45, Part 46 issued CIOMS Guidelines for Epidemiological studies
1989 WMA updates DOH (Hong Kong)
1983 WMA updates DOH (Venice)
1981 US Common rule updated
1979 The Belmont Report
1975 WMA updates DOH (Tokyo)
1966 Dr. Beecher’s Article “Ethics and Clinical Research”
1964 World Medical Association (WMA) published the Declaration of Helsinki (DOH)
1947 The Nuremberg Code
1900 Walter Reed’s ‘consent’ for yellow fever experiments
Pre-1900 Edward Jenner smallpox vaccines

14. 18th and 19th Centuries
 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)

15. Nazi Doctors’ Experimentation

16. 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

17. 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

18. The Declaration of Helsinki (DOH)
 The World Medical Association created the Declaration of
Helsinki in 1964 and amended regularly since 1975
The main issues emphasized were:
 “The well-being of the subject should take precedence over
the interests of science and society”
 Consent should be in writing
 Use caution if participant is in dependent relationship with
researcher
 Limited use of placebo
 Greater access to benefit

19. 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

20.  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 )

21. The Belmont Report (1979)
 1972: the public became aware of the Tuskegee study
 1974: the National Commission for the Protection of Human
Subjects of Biomedical and Behavioral Research was established.
 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.

22. 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

23. 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.

25. WHAT’S ETHICALLY
UNIQUE ABOUT
MOLECULAR BIOLOGY AND
BIOTECHNOLOGY?
Ethical Issues in research on
humans

26. Very rapidly progressing…

27. Very wide possibilities…
 Identification of the genes responsible for human diseases,
 Identification of the mutations underlying a vast number of
phenotypes
 health care (medical), crop production and agriculture, non
food (industrial) uses of crops and other products
 Examples:
 biodegradable plastics, vegetable oil, biofuels), and
environmental uses.
 manufacture of organic products (e.g. milk products)
 Used to recycle, treat waste, cleanup sites contaminated
by industrial activities (bioremediation), and
 to produce biological weapons.

28. Examples of 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)
• INTEGRITY & PUBLICATION ETHICS

29. Benefits
 Benefits to research subjects
Direct Benefit
 Arising from the intervention being studied
 Information that can influence care, e.g., diagnostic
Collateral “indirect” Benefit
 Extra supervision from being in the research study (?)
 Access to medical care not available for economic reasons
 Unplanned or unanticipated benefits
 Payments or incentives – benefits?
 Benefits to society
• Specific new, effective intervention
• Knowledge which some time in the future may lead to effective interventions

30. Types of Risk…Cont.
Physical (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)

31. 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 their nutrition and houses.
Environmental Risks:
Manipulating environmental factors (Pathogenic
organisms and toxic chemicals).

32. 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

33. 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.

34. 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 specialized committees should make a complete risk
assessment for the use of the hazardous substances .

35. 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.
For Psychological Risks :
 Sensitive questions for sensitive group like those with AIDS,
STDs, T.B, need to be asked by experiences researchers and ask
the help of psychologists may be needed.
Economic Risks :
 Traveling cost can be solved out.
 Absentees issues should also be solved out.

36. 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.

37. 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.

38. Vulnerability
(Risk-Vulnerability Matrix)

39. Definition
 Vulnerable: “Vulnerable persons are those who are
relatively (or absolutely) incapable of protecting
their own interests due to insufficient:
 power,
 intelligence,
 education,
 resources strength,
 or other needed attributes to protect their own interests.”
(CIOMS, 2002)

40. Who is Vulnerable?
M A K I N G U S E O F T H I S D E F I N I T I O N … L E T ’ S
B R A I N S T O R M !
www.amanet-trust.org

41. 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.

42. 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

43. 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.

44. 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.

45. 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

46. 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.

47. 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

48. 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.

49. 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.

50. 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

51. 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.

52. 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

53. Risk/Vulnerability Matrix

54. 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

55. Informed Consent

56. 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

57. 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.

58. Disclosure
VoluntarinessCapacity

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

60. 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

61. 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

62. 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

63. 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

64. 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

65. 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

66. Principles for Providing Information to
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

67. 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)

68. 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.

69. 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

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

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

72. 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.

73. 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?

74. 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

75. 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

76. Privacy and confidentialityPRIVACY &
CONFIDENTIALITY

77. Privacy
The right to be left alone and to keep
personal information inaccessible to
others (the condition of limited access
to a person)

78. 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

79. 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

80. 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

81. 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

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

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

84. 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?

85. Conflicts of Interest (COI)
CONFLICTS OF
INTERESTS

86. 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.

87. 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

88. 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

89. 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)

90. 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.

91. 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.

92. 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

93. 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

94. 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

95. • 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.

96. • 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,

97. 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

98. 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.

99. 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

100. 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

101. 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.

102. 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.

103. 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.

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

105. 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

106. Ethical Review of
research

107. 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.

108. 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.

109. 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.

110. Case studies and examples