Research Ethics

Dr Olayinka R. Eyelade, FWACS

Reader/Consultant Anaesthetist
Department of Anaesthesia
College of Medicine , University of Ibadan/ UCH
Ibadan
Email: dryinka@yahoo.com
WACP Course in Medical Ethics – 6 August, 2020
 Introduction
• Research connotes different meanings to
different individuals

• Past history of abuse of human research

participants

• Therefore there is a need to have ethical

norms that will guide the conduct of research

Research ethics - WACP Ethics Course,

August 2020
What is Research?

Research ethics - WACP Ethics Course,

August 2020
 Research Ethics
• a set of rules that inform research design,
conduct, analysis, dissemination and
implementation

Research ethics - WACP Ethics Course,

August 2020
 Lecture Contents
1. Regulatory bodies in ethics and the National
Code
2. The meaning and justification of Informed
consent – Competence, Voluntariness,
Disclosure, Understanding, Authorization
3. Conflicts of Interest

Research ethics - WACP Ethics Course,

August 2020
 Lecture Contents
4. Benefits and Inducements

5. Justice

6. Surrogate decision making

Research ethics - WACP Ethics Course,

August 2020
 Research - Definition
• Regulatory definition
“a systemic investigation, including research
development , testing and evaluation,
designed to develop or contribute to
generalizable knowledge..”

Ref: Nigerian National Code of Health Research Ethics available at

www.nhrec.net

Research ethics - WACP Ethics Course,

August 2020
 Ethics

Research ethics - WACP Ethics Course,

August 2020
 1.Regulatory bodies in ethics –
a. Nuremberg Code
The Summary of
the Code
1.Informed
Consent
2.Qualified
Prisoners of researchers using
war The trial appropriate
led to research design
3.Favourable
risk/benefit ratio
4.Participants
free to stop at
The any time
trial

Research ethics - WACP Ethics Course,

August 2020
 b. The Declaration of Helsinki
First declared in 1964, has been revised several times
Summary: The well-being of the subject should take
precedence over the interests of science and society.
➢Written consent
➢Caution if participants is vulnerable
➢Limited use of placebo
➢Benefits for individuals and community
Ref: Carlson et al 2004. The Revision of the Declaration of Helsinki: past
present, and future. Br J Clin Pharmacol 57: 695-713

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August 2020
 c. The Belmont Report
The Tuskegee Study –
✓Respect for
1932 - 1972
Persons- self
determination,
capacity to decide,
informed consent

✓Beneficence –
protection of
participants,
benefits
“Special treatment” - A 1933 photo
of a subject undergoing a lumbar ✓Justice –
puncture (spinal tap). (Archives of equitable
the Center for Disease Control, recruitment of
Tuskegee Study Files.)” research
participants,
distribution of risk
and benefit
Research ethics - WACP Ethics Course,
August 2020
 d. The U.S. Code of Federal Regulation
• Prior approval by ethics committee
• Well written informed consent and
documentation
• Equitable recruitment of research participants
• Special protection of vulnerable groups
(children, pregnant women, women, poor
people and people with limited education)
• Continue review of approved research

Research ethics - WACP Ethics Course,

August 2020
e. Council for International Organizations of
Medical Sciences (CIOMS)
• Research in developing countries
• Informed consent
• Protection of vulnerable population
• Role of Research Ethics Committee
• Community Participation

Research ethics - WACP Ethics Course,

August 2020
 f. International Conference on
Harmonization (ICH)
• Standardize drug development and approval
process
• Review by ethics committee: research design,
conduct, analysis, dissemination and
implementation
• Researcher/sponsor responsibilities

Research ethics - WACP Ethics Course,

August 2020
 g. Nigerian National Code of Health
Research Ethics

Nigerian National Codes

Protest
by
The Trovan study in
parents/
Nigeria by Pfizer in
guardian
1996

Ref: Annas JG. 2009. Globalized clinical

trials and informed consent. N Eng J
Med 360.20:2050-2053.

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August 2020
What make clinical research ethical
• Value-enhancement of health or knowledge
must be derived from the research
• Scientific validity – the research must be
methodologically rigorous
• Fair subject selection-scientific objectives
• Favourable risk-benefit ratio

Research ethics - WACP Ethics Course,

August 2020
What make clinical research ethical
• Independent review
• Informed consent
• Respect for enrolled subject – privacy
protected, confidentiality, opportunity to
withdraw, and their well-being monitored.
• Standard of care; reasonable availability of
interventions

Research ethics - WACP Ethics Course,

August 2020
 2. The meaning and justification of
Informed consent
Informed consent may be defined as a process
whereby an autonomous individual authorizes
a health care provider to initiate medical
intervention or involvement in research

Research ethics - WACP Ethics Course,

August 2020
 Informed Consent - Origin
• Historical events in medical practice – in this
context, informed consent was seen as a
protection from abuse by untrustworthy
professionals
• Shift in medical decision making from
beneficent paternalism of professionals
towards a patient autonomy model ( Berg et
al 2001)

Research ethics - WACP Ethics Course,

August 2020
Informed Consent – an Event and a Process

• But mostly a process (Belmont Report

1979)
• An event – in the context of
“official/legal/ethical
duty” of the healthcare provider
• A process – here it is perceived as a continuous
relationship between patients and their
caregivers; the patients too have an active role
to play
• Shared – decision making
Research ethics - WACP Ethics Course,
August 2020
 Informed consent - competence
• Competence:
– Ability to perform a task (by subject)
– Competency determination is task specific
– Competency is a continuum, ranging from full
competence to full incompetence
– Where incompetence is affirmed, surrogate or
other decision standards are applied

Research ethics - WACP Ethics Course,

August 2020
 Informed consent - Voluntariness
• Voluntariness:
– Are there external influences on the patient?
– Voluntariness means free of others’ influence
– Subject alone wills the action
– Withholding and manipulating information
negates voluntariness
– Coercion, fear, use of force affect voluntariness
negatively

Research ethics - WACP Ethics Course,

August 2020
Informed consent - Understanding
• Understanding:
– Without this, no autonomous authorization
– Lack of understanding brings interference
– Distinction between substantial and full
understanding
– Language is important

– Substantial understanding means recognition of

consent as act of authorization
Research ethics - WACP Ethics Course,
August 2020
 Informed Consent - Authorization
• Consent:
– Actual decision making or authorization

– Subject autonomously authorizes professional

– Consent is ongoing in that it is a process rather

than a static event
• Consent Form, Documentation; Guidance,
witness

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August 2020
Informed consent - Elements
• Understandable language
• Purpose of study, procedures to be
undertaken or the treatment
• Anticipated results
• Alternative treatments
• All foreseeable risks & discomforts
(physical, psychological, social,
economic, inconvenience)
• Benefits

Research ethics - WACP Ethics Course,

August 2020
 Informed consent - Elements (2)
4. Disclosure of appropriate alternatives
5. A statement about maintenance of
confidentiality
6. For research involving more than minimal risks,
an explanation about possible compensation if
injury occurs
7. Information about how the patient can get
pertinent question answered
8. A statement that participation is voluntary (
refusal to participate involves no penalties or loss
of benefit
Research ethics - WACP Ethics Course,
August 2020
 Informed Consent - Exceptions
Exceptions to Informed Consent
1.Emergency/life saving treatment to prevent
death or harm
2. Patients unable to consent (incompetence).
Other standards
3. Public health requirements – public Interest
4. Therapeutic privilege – harm feared is from
disclosing information, not treatment.

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August 2020
 Types of Informed Consent
• Consent: An adult who is 18 years or older in age,
competent of personal choice make a decision to
participate.
• Parental Permission: When children or minors
are included in research, parent / guardian must
sign a Parental Permission Consent document.
• Assent: is a child’s affirmative agreement to
participate in research: applicable to children 7 –
17 years. Informed consent must be at the
reading level of a 7 year old.
Research ethics - WACP Ethics Course,
August 2020
 Types of Informed Consent (2)
• Verbal: contains all the elements of written
consent, however, the participant is verbally
read the elements and verbally agrees to
participate.
• Short Form: is generally used when there is a
language barrier and an English ethics
committee approved consent is orally
translated in the participants' native language

Research ethics - WACP Ethics Course,

August 2020
 Informed consent - Surrogacy
• Legal representative

• Guardian/caregiver/parent, family member

• Legal instruments: advance directive

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August 2020
 3. Conflicts of Interest –Definition(s)
• a set of conditions in which professional judgment
concerning a primary interest tends to be unduly
influenced by a secondary interest
• a clinical role conflict between professional duties to
a patient and obligations (express or implied, real or
perceived) to the interests of a third party
• relationships with industry that may unduly
influence or supersede the primary interest of a
researcher/clinician

Research ethics - WACP Ethics Course,

August 2020
 Conflicts of Interest - Examples
• self-referral by physicians
• gifts and incentives from drug companies to
physicians
• hospital purchasing and bonding practices
• industry-sponsored research
• research on patients

Research ethics - WACP Ethics Course,

August 2020
 Conflicts of Interest – Examples 2
• consulting fees or compensation for personal
services to a company
• equity or other ownership interests
• royalties
• intellectual property rights

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August 2020
 Consequences of Conflict of Interest
• a conflict of values
• a conflict of commitments
• dual loyalty
• potential for scientific misconduct

Research ethics - WACP Ethics Course,

August 2020
Aims of regulating Conflicts of Interest
• To maintain the integrity of professional
judgment
• To maintain confidence in professional
judgment
• To enhance and maintain scientific objectivity
• To eliminate/minimize potentials for scientific
misconduct

Research ethics - WACP Ethics Course,

August 2020
 Remedies for Conflicts of Interest (COI)

• prevention
• individual discretion
• delegation of key research activities
• development of protocols and guidelines
• professional regulation
• governments regulation

Research ethics - WACP Ethics Course,

August 2020
 Benefits and Inducement
• Inducement, in the context of research, is a reward given to
anyone who volunteer to participate in a research

• The examples of inducement are free care, medical

examination, provision of drugs, gifts, and cash. Payment of
cash appears to be the most common type of inducement
(Dicket et al, 2002).

Research participants may be reimbursed for:

• Transport and other expenses including lost earnings
associated with their participation in the research
• Medical services that are related or unrelated to the research
• Inconveniences and time spent in participating the research

Research ethics - WACP Ethics Course,

August 2020
 Benefits
• In therapeutic research –benefits may include relief
from disease, diminished suffering or provision of
diagnostic information
• In non-therapeutic research participants join for
altruistic reasons to benefit society
• In exchange for these benefits, participants accept
some risk. Acceptability of these risks reflect the
participants goals and values. Payment may
influence these calculations

Research ethics - WACP Ethics Course,

August 2020
 Some challenges of inducement/benefits
• It is sometimes difficult to distinguish between
acceptable inducement and undue influence to
participate in research in some settings

• For example, an unemployed person or student may

view payment differently from an employed person

• Someone without access to care may or may not be

unduly influenced to participate in research simply
to receive such care

Research ethics - WACP Ethics Course,

August 2020
 Some challenges of inducement/benefits
• For example, in the trial of the drug Trovan by
Pfizer, any patient who wanted good quality care
must enroll in the study because the best available
bed space was offered to anyone willing to
participate

• A prospective research participant may be induced

to enroll in research to obtain a better diagnosis or
access to a drug not otherwise available (CIOMS,
2002)

Research ethics - WACP Ethics Course,

August 2020
 Benefits/inducement - summary
• All payments, reimbursements and medical services
provided to research participants must be approved
by the Ethical Review Committees

• Monetary and in-kind payment must be evaluated in

the context of the traditions of the particular culture
and population in which they are offered, to
determine whether they constitute undue influence

Research ethics - WACP Ethics Course,

August 2020
 5. Justice
• Justice can be described as Virtue of the
individual, as in a just man

• To be just is to act fairly and justly

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August 2020
 Types of Justice
- Lawful/law abiding person (universal justice)
- One who does not want more. (this is
particular justice, and it comes in two ways: a)
regarding distribution (Distributive justice)
- and b) regarding correction (Corrective
justice)

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August 2020
 Distributive Justice
- This deals with goods that can be distributed among citizens,
such as money, honor, power, health care, etc.
- Avoid the extremes of too little & too much
- Keep to the middle which is the equal
- Also recognize that there are two people
- Each person is given as he deserves
- Thus, the 2 extremes and 2 people are the terms that
determine equality. Distribute according to need.
- Such equality is proportional, not mathematical equality.
(Nichomec. Ethics, Bk. V, ch. 3)

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August 2020
 Corrective Justice
- This deals with correcting disorders that have arisen
in human exchanges, e.g., theft, injury, abuse, etc.

- Here, justice is rendered not considering the person

but the thing damaged and what is appropriate to
replace it.

- Here, the quality of the person does not play a role.

Instead, the judge determines the damage done and
how the loss can be restored. In this too, justice is
the middle between loss and gain (N.E., Bk. V, ch.
4).

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August 2020
 Rawls’ Theory of Justice
• Theory based on the social contract developed by
Locke & Rousseau

• Based on developments made on the social contract,

he presents justice as fairness

• Citing conflicts that occur as a result of mutual

interests among people, Rawls presents a set of
principles to guide the selection of social
arrangements that would distribute benefits and
burdens fairly.
Research ethics - WACP Ethics Course,
August 2020
 Rights & Duties
• Justice as fairness translates into rights and
duties for each individual in the original
position.
• The concept of right is based on the fact that
all the principles reached in an agreement is
applicable to all parties alike.
• Such principles that are the object of the
concept of right apply to all individuals in their
relation to each other. (Rawls, 95)

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August 2020
 Justice: Implications for Research Ethics
• What are the terms to be considered in
making sure that participants of both arms of
a research study are treated equally? What
type of equality?

• Could researchers be made to compensate

research subjects for damages suffered due to
participation in research studies?

• Role of Informed consent. ?contractual

agreement
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August 2020
 6. Surrogate Decision making
If a patient is not competent to choose or to
refuse treatment, a hospital, a physician or a
family member may justifiably exercise a
decision- making role or go before a court or
other authority to resolve the issues before
implementing a decision.

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August 2020
 Standards of Surrogate decision making

1. Substituted judgement

1. Pure autonomy

1. Patient’s best interest

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August 2020
 Substituted Judgement
• Is a weak autonomy
• Asserting that what the majority of
reasonable people would choose or what the
incompetent person would choose if
competent
• ‘Reasonable’ ‘Just’

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August 2020
 Pure autonomy
• Applies to formerly autonomous now
incompetent patients who expressed a
relevant autonomous preference (written or
oral)
• A person can designate another by a durable
power of attorney to make medical decisions
on his/her behalf through the use of advance
directive

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August 2020
 Best Interest
• Under the best interests, a surrogate decision
maker must determine the highest net benefit
among available options.
• The best interest protects another’s well-
being by assessing risks, pain & suffering, and
by evaluating restoration or loss of
functioning (Quality of life)

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August 2020
 Best Interest - 2
• If the designated surrogate makes a decision
that clearly threatens the patient’s best
interests, the decision could be overridden
unless there is a clearly worded second
document executed by the patient that
specifically supports the surrogate decision.

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August 2020
 References
• Beauchamp T.L. & Childress J.F. 2001. (Eds). Principles of
Biomedical Ethics. Oxford University Press.
• Berg JW, Appelbaum PS, Lidz CW & Parker LS. Informed
consent : Legal Theory and Clinical Practice. 2nd edition.
Oxford University Press 2001.
• 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
• Dicket N, Emmanuel E and Grady C. Paying research subjects:
an analysis of current practices. Annals of Internal Medicine,
2002, 136 (5): 368-373

Research ethics - WACP Ethics Course,

August 2020