Lecture 18 research ethics (1)

Ghaiath Hussein, MBBS, MHSc. (Bioethics), Doctoral Researcher (UK)
Assistant Professor of Bioethics

Outline
■ Research in context: the Knowledge
Management Cycle (KMC)
■ historical background on research
ethics
■ What makes research ethical?
■ Definition and examples of scientific
misconduct
■ How to make your research ethical and
avoid scientific misconduct?

Where are we in R&D?
Source: http://www.worldmapper.org/display.php?selected=165

Where are we in R&D?
Expenditure on R&D as
% of GDP (2013):[1]
– Arab world: 0.5%
– China (2%),
– EU (2.3%),
– USA (2.8%),
– Israel (4%)
Number of researchers (per
1,000,000 population) [2]
■ Morocco : 864
■ Argentina: 1,236
■ Malaysia: 1,643
■ Slovenia: 4,255
■ Israel: 6,494
Published scientific papers (1996 -2013):[3]
Egypt (42nd): 104,784 Brazil: 529,841
Israel: 247,561 India: 868,719
Turkey: 348,836 USA: 7,846,972

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

Research in Context...the KMC
Generation
Dissemination
Synthesis
Utilization
Assessment
Statistics

Better Research is Better Health
“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

Good
Science
•Problem selection
•SMART objectives
•Proper methodology
•Proper analysis
•Fair subject selection
•Favorable Risk-Benefit Ratio
•Independent Review
•Informed Consent

Criteria of “Good” Science Research
■ Systematic: The research developed,
implemented and reported in a systematic
manner.
■ Methodological: 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.

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

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

Lecture 18 research ethics (1)

History of Research Ethics
Pre-World War II: Research standards left up to the discretion of
the individual researcher
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)

World War II: Nazi Doctors’ Experimentation
Experiments conducted on inmates of Nazi concentration camps
1945-1949:Trials in Nuremberg, Germany– physicians convicted of crimes against
humanity

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:
■ Voluntary consent absolutely essential (restricting
research with infants, children, developmentally
challenged, etc.)
■ Freedom from coercion
■ Comprehension of the risks and benefits involved
■ Experiment to be conducted by highest qualified persons
■ Risk/Benefit Analysis essential to ethics review
■ Scientific Soundness is important to ethics review
The code on the web: http://ohsr.od.nih.gov/nuremberg.php3

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”
 Respect for Persons – people are not a means to an end;
researchers have duty to protect life, health, privacy and
dignity of research participants
 Consent should be in writing
 Standard of care must be best available, even for control
group
 Greater access to benefit
 Use caution if participant is in dependent relationship with
researcher
 Limited use of placebo

 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 )

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.

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

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.

EXAMPLES OF
ETHICAL ISSUES IN
RESEARCH

Some ethical issues in research
Before
•Benefit/harm
analysis
•Vulnerability
(Risk-
Vulnerability
Matrix)
•Fair selection of
participation
•Conflict of
Interests (COI)
During
•Informed
Consent
•Privacy and
confidentiality
•Risk to
researchers
•Risk to
participants
After
•Sharing results
•Sharing
benefits
•Integrity &
publication
ethics

Core ethical principles/issues in research
(Source: WHO Training manual: Ethics in research, surveillance and patient care in epidemics, emergencies and disasters,
WHO (2014))
Ethical
principle/issue
Definition1 Examples of
guidelines
Respect for
people’s
autonomy
The duty to respect people’s ability to
make decisions on issues related to their
health and their body, if they are
competent to make such decisions; and the
duty to protect individuals with impaired
or diminished autonomy
CIOMS,
General
principles
TCPS,
article 1.1
Belmont
Report

(Source: WHO Training manual: Ethics in research, surveillance and patient care in epidemics, emergencies and
disasters, WHO (2014))
Ethical
principle/issue
guidelines
Beneficence The moral duty to pursue actions that promote the
well-being of others and the ethical obligation to
maximize benefit and to minimize harm
CIOMS, Belmont
Report,
Non-
maleficence
The moral duty not to cause harm to others
through interventions
CIOMS,
DOH (articles
16–18)
Justice Primarily distributive justice, which requires
equitable distribution of benefits and burdens, i.e.
distribution such that no segment of the
population is unduly burdened by the harms of
research or denied the benefits of the knowledge
generated from it
CIOMS
(guidelines 10
and 12)
DOH (articles
16–18)
TCPS (article 1.1
and Chapter 4)

(Source: WHO Training manual: Ethics in research, surveillance and patient care in epidemics, emergencies and disasters, WHO
(2014))
Ethical
principle/issue
guidelines
Vulnerability A status in which some people may struggle to
protect their interests or be at greater risk of being
exploited. This situation is usually linked to specific
physical, financial, educational or social
circumstances.
Groups considered as vulnerable vary by guideline,
but children, mentally retarded and handicapped
people, prisoners, refugees, terminally ill patients
and women are often cited as the prime vulnerable
groups.
CIOMS ( guidelines
13–16), DOH (articles
19 & 20)
Common rule,
subparts B, C and D
TCPS (Chapter 9)
Privacy The right or expectation not to be interfered with or
to be free from surveillance or, more generally, a
moral right to be left alone. In practical terms,
privacy is for instance concerned with the setting in
which a person’s health-related information is
acquired.
TCPS (Chapter 5),
DOH (article 24)

(Source: WHO Training manual: Ethics in research, surveillance and patient care in epidemics, emergencies and disasters,
WHO (2014))
Ethical
principle/issue
guidelines
Confidentiality The principle that ensures that identifiable
information is kept out of reach of others.
All identifiable information about
individuals, whether recorded (written,
computerized, visual, audio) or simply held
in the memory of health professionals, is
subject to the duty of confidentiality.
CIOMS (Guideline
18), TCPS (Chapter 5)
Research
ethics review
A process by which a group of experts in
research, ethics and other disciplines decides
whether a research protocol fulfils the ethical
standards of research before being
undertaken
CIOMS, Guidelines 2
and 20; Common
Rule, subpart A,
(articles 46.107,
46.108 and 46.109);
DOH (article 23);
TCPS (Chapter 6)

What is IC?
■ A process whereby potential research
participants decide whether they want to
participate in the proposed study after
receiving information about it.
■ Decisions must be made free from coercion,
by a competent person who can understand
the information given and appreciate the
associated risks.
■ The information given to the participant
should be in a language and format suitable
to the participant’s ability to comprehend it.

Components of IC:
1. "Disclosure" refers to the provision of relevant
information by the clinician and its
comprehension by the patient. This refers to the
process during which physicians provide information
about the proposed research to the participant
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.

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
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

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

Waiver of Informed Consent
Conditions to waiver IC:
 Poses no more than Minimal risk
 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

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

Principles for Providing Information to Participant:
Make it clear; avoid jargon
Use language appropriate to the
participant’s level of understanding in a
language of their fluency
Invite questions from the patient and
check for understanding
Summarize the imparted information
Provide contact information (and other
resources)

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.

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

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
KSA.

CONFLICTS OF INTEREST
(COI)
Conflicts of interests

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.

What is COI?
• 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
• COI exists when two or more contradictory interests
relate to an activity by an individual or an institution.
• “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

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
• 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

Levels of COI
1- Researchers
•The REC should assess the likelihood that
the researcher’s judgment may be
influenced, or appear to be influenced, by
private or personal interests (TCPS, 2000)
2- Conflicts of Interest by REC Members
•It is of the highest importance that
members of the REC avoid real or apparent
conflicts of interest .
•E.g.: their research are reviewed by their
REC or when they have been in direct
academic conflict or collaboration with the
researcher whose proposal is under review.

Levels of COI
3- 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 REC must act independently from the
parent organization.
• Institutions must respect the autonomy of the
REC and ensure that the REC has the
appropriate financial and administrative
independence to fulfill its primary duties.

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 a collegial enterprise
4. Exploitation of trainees
5. Transfer of time and interest to
commercial ventures

Practical Steps to resolve COI
•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

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.
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.

Research Misconduct (FFP)
Research misconduct is defined as fabrication, falsification, or
plagiarism in proposing, performing, or reviewing research, or
in reporting research results.
– Fabrication is making up data or results and recording or
reporting them.
– Falsification is manipulating research materials,
equipment, or processes, or changing or omitting data or
results.
– Plagiarism is the appropriation of another person’s ideas,
processes, results, or words without giving appropriate
credit.
– Research misconduct does not include honest error or
differences of opinion.
– Research misconduct includes the destruction of, absence
of, or accused person's failure to provide research records
accurately documenting the questioned research.

Office of Research Integrity
(ORI)’s Definition of Plagiarism
■ … plagiarism to include both the theft or misappropriation
of intellectual property (IP) and the substantial
unattributed textual copying of another's work. It does not
include authorship or credit disputes.
■ … the unattributed verbatim or nearly verbatim copying of
sentences and paragraphs which materially mislead the
ordinary reader regarding the contributions of the author.
■ The theft or misappropriation of intellectual property (IP)
includes the unauthorized use of ideas or unique methods
obtained by a privileged communication, such as a grant or
manuscript review.

Forms of misconduct
■ Falsification ‫التزوير‬
■ Obfuscation‫التضليل‬
■ Fabrication‫التلفيق‬
■ Plagiarism ‫سرقة‬
‫فكرية‬
■ Self-plagiarism
■ Ghost writing ‫الكتابة‬
‫الشبحية‬
■ Bare assertions
‫دليل‬ ‫بال‬ ‫التأكيد‬
■ Improper authorship
■ Misappropriation‫اخت‬
‫الس‬
■ Bibliometric inflation
■ Violation of ethical
standards
Source: http://en.wikipedia.org/wiki/Scientific_misconduct

How to maintain research ethics
and avoid scientific misconduct?
Before conduct of
research
• Develop clear
research plan
(who will do what
when and how)
• Submit protocol
to ethical review
• Prepare
(communicate)
well with your
research
community
• Agree on
authorship
During conduct of
research
• Follow the
approved protocol
• Gain consent
• Involve the
community
• Protect yourself,
your team, & your
participants
• Regularly check
your data
After research
• Share your study
report(s) with
• Return
‘something’ back
to the researched
community
• Publish following
publication ethics
• Use Reference
Management
Software

References
1. World Bank’s interactive website:
http://data.worldbank.org/indicator/GB.XPD.RSDV.GD.ZS
2. World Bank website:
http://data.worldbank.org/indicator/SP.POP.SCIE.RD.P6?orde
r=wbapi_data_value_2011+wbapi_data_value&sort=desc
3. SCImago. (2007). SJR — SCImago Journal & Country Rank.
Retrieved December 09, 2014, from
http://www.scimagojr.com
4. Training manual: Ethics in research, surveillance and patient
care in epidemics, emergencies and disasters. Geneva,
Switzerland: World Health Organization; 2014.

This presentation and more material can be found online:
http://www.slideshare.net/ghaiath
https://www.youtube.com/ghaiathme
• You may also contact me on my email: ghaiathme@gmail.com

Lecture 18 research ethics (1)

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Lecture 18 research ethics (1)