Transcript “Ethics from fundamentals to justice & fair-play” Sisira Siribaddana Forum for Research & Development.

“Ethics from fundamentals to
justice & fair-play”
Sisira Siribaddana
Forum for Research & Development
Introduction to bio ethics
(this section is adapted from slides by
Doug Wassener)
What is the role of ethics in
research with human participants?
• The objective of clinical research is to develop
generalizable knowledge to improve health and/
or increase the understanding of human
biology
• The aims of research are a recognized good,
but research has the potential to inflict harms
and to treat participants as just “means to an
end”
• The aim of ethics is to ensure that participants
are treated with dignity and respect while they
contribute to the social good
• Ethics may help us find the ‘least harmful’ route
What is the role of ethics in
research? cont’d
• Ethics aims to protect participants from harm
and to promote their welfare:  acts to
restrain science
• However, ethics also promotes good science
as participants who feel respected may:
– Actively engage with research requests
– Answer truthfully
– Provide critical & honest feedback
– Return for follow up
– Therefore increasing the quality of the data
What are the key principles
in research ethics?
• NON-MALEFICENCE: “Do no harm”
• There should be no intentional injury or harm
to participants as a result of participation;
researchers are obligated not to deliberately
harm participants
• BENEFICENCE: Minimize potential harms &
maximize expected benefits of the research;
Researchers should take active and positive
steps to reduce possible harms to a minimum
and to maximize anticipated benefits of the
research
– In some research there may be no direct benefit for
the participant, but benefits to society in terms of
important knowledge
What are the key principles
in research ethics cont’d?
• RESPECT FOR AUTONOMY: “self-rule”
• A person’s freedom of thought & action
should be respected and researchers
must respect rights of participants who
can make decisions to do so
• Researchers must take special measures
to protect vulnerable participants whose
freedom to make choices is limited, or
those with no capacity to choose
What are the key principles
in research ethics cont’d?
• JUSTICE: Fair balance of risks and benefits
• Those who stand to benefit from research must
contribute to its risks and discomforts
• No group of persons should be asked to bear more
than their fair share of the burdens of research; no
group (e.g. impoverished) should be asked to bear
research risks in order that others (e.g. the wealthy)
enjoy benefits (new knowledge or products)
• International collaborative research growth
• No group should be deprived of fair access to the
benefits of research; No class of person should be
unfairly excluded from research (e.g. women) as this
denies them relevant knowledge/ health
interventions
What makes research ethical?
The requirements for ethical research:
1 Community Participation
2 Social value
3 Scientific validity
4 Fair selection of participants
5 Favorable risk / benefit ratio
6 Independent review
7 Adequate informed consent
8 Ongoing respect for dignity
Community participation
• Rationale: Based on right and responsibility to
participate in research development activities;
and can offset potential vulnerabilities.
• Mechanisms: Include the formation of a
Community Advisory Board (CAB).
• Possible role: Includes inputs to design
(e.g. IC); advising on cultural conventions,
expectations; evaluating impact of the
research.
• Community participation should be based on a
genuine partnership geared towards mutual
respect, education & consensus building.
Community participation cont’d
• Benefits of community participation include:
– Enhanced cultural appropriateness
– Increased acceptability of the research to
the participating community
– Fairness and equity regarding important
decisions (e.g., adequate incentives)
– Sound bi-directional information exchange.
• E.g.,in preparation for HIV vaccine trials in
South Africa community structures are being
formed at sites (e.g. Gauteng CAB and interim
DBN CAB).
Community participation cont’d
• Complexities:
• Defining community: which stakeholders
and interest groups must be represented?
• Difficulties in ensuring mandated
representation
• Defining “participation” (from recipients of
education  full and equal partners)
• Determining what “participation point” on
the research continuum? (from protocol
development  dissemination of results)
What makes research ethical?
1. Social or scientific value
• To be ethical, research must be valuable
• Society should gain important
generalizable knowledge.
• Why? Researchers can not expose human
beings to inconvenience or risk of harm
without possible benefit to society
What makes research ethical?
2. Validity
• Even a valuable question can be poorly
researched, resulting in unreliable data.
• Research must also be well designed and
conducted (e.g. clear aims, rigorous
design, adequate sample, adherence to
GCP, sound data analysis).
• Why? Poorly designed & conducted
research is unethical as it exposes
subjects to risks and inconvenience for no
purpose.
What makes research ethical?
3. Fair choice of participants
• Selection of participants should be fair and
just.
• Firstly: Participants should be chosen
according to the scientific goals of the study
and not for non-scientific reasons (E.g. not
acceptable to select participants because
they are convenient, or vulnerable, or less
able to protect their rights).
• Also, participants should not be excluded
from research without sound justification (E.g.
while pregnant women will be excluded from
HIV vaccine research, justifications will rest
on potential risks to the foetus).
What makes research ethical?
3. Fair choice of participants
• A challenge for researchers is to address
potential misperceptions that vulnerable
individuals and communities will be
unjustly targeted, and to demonstrate
safeguards that will be taken to offset
specified vulnerabilities.
• This is important in international
collaborative research between developed
and developing countries.
What makes research ethical?
3. Fair choice of participants
• Secondly: Volunteers should be chosen to
minimize risks.
• It is possible that potential participants will be
eligible for scientific reasons, but they may be at
substantially higher risk of harm (e.g.
impoverished and vulnerable to undue
inducements).
• “Rule of thumb”: Researchers should avoid
involving the vulnerable when less vulnerable
persons could be involved, must justify why
vulnerable persons are included, and articulate
safeguards to minimize risks for vulnerable
persons and communities.
•
See MRC (2002) book 1
What makes research ethical?
3. Fair choice of participants
• Thirdly, individuals and communities
should be selected so that the benefits
and burdens are fairly distributed.
• Individuals and groups who bear the
burdens of the research should share its
benefits (new knowledge or products).
E.g., after phase I trials, knowledge or
other benefits should be made available to
participating individuals and communities;
e.g., after phase III trials, any successful
vaccine should be made reasonably
available to participants and community.
What makes research ethical?
4. Favorable risk- benefit ratio
• The potential risks to individual participants
must be identified and minimized.
• The potential benefits of the research must be
identified and maximized.
• The potential risks to individual participants
should be outweighed by the benefits to the
individual - or society (favorable risk-benefit
ratio).
What makes research ethical?
4. Favorable risk-benefit ratio
• Risk minimization measures must be
undertaken:
E.g. in HIV vaccine trials:
– Ongoing monitoring for effects
– Risk reduction counseling (optimal)
– Counseling around possible negative
consequences (e.g. stigma) of disclosure
– Provision of support counseling
– Testing to differentiate between antibody
response and natural infection; ID card; and
support.
What makes research ethical?
4. Favorable risk-benefit ratio
• The potential risks to individual subjects
should be outweighed by the benefits to the
individual or society:
• Who decides this?
– Research ethics committees at every
participating institution
– Participating communities via
establishment of representative
participatory structures
– Each and every individual via informed
consent.
Maximizing benefits:
Access to successful products
• E.g., Ensuring access to an HIV vaccine that is
demonstrated to be safe and effective:
South African AIDS Vaccine Initiative:
– Planning is being undertaken now to ensure
that once a successful vaccine is developed
will be accessible and affordable to SA
– E.g. AlphaVax – IAVI agreement that spells
out commitment to pricing close to cost if
licensed.
– Access to ART for seroconverters: Required
– mechanism being finalised (cf. Lancet…)
What makes research ethical?
4. Favorable risk-benefit ratio
•
•
•
•
Use of placebo controls:
Unease of public:
From 1) “deceptiveness” or
2) appears to consign placebo group to an
“unfair disadvantage”
• Placebo controls may be regarded as
acceptable if “clinical equipoise” exists, if
there is no comparator, (?assay sensitivity
even if there is a comparator (Temple)
What makes research ethical?
5. Independent review
• Researchers operate at the interface of
multiple obligations and interests
– undertake research; publish; acquire
funding; further careers; protect human
subjects
• These conflicting interests can potentially bias
how researchers perceive their research
designs and conduct research
• Research should be reviewed by persons
independent of the research (“at arm’s
length”).
• But REC’s should be competent and confident
to review complex designs.
What makes research ethical?
5. Independent review
• Review process examines the scientific
and ethical quality of the research,
minimizes conflicts of interest, and aims
to ensure that participants are protected
and treated with dignity (1, 2, 3, 4, 6, 7).
• In upcoming phase I HIV vaccine trials, the
protocols must be reviewed and approved
by the FDA in the USA, the MCC in SA, and
ethics committees at every participating
institution (E.g. Nelson Mandela REC, Wits
REC, MRC REC and Institutional Review
Boards in the USA).
What makes research ethical?
6. Informed consent
• Research participants have a right to
choose freely whether or not to participate
based on an understanding of all relevant
information.
• This ensures that participants will only
take part if the research is consistent with
their interests, values and preferences
(autonomy).
• Easier to assert than to assure in
developing country contexts
•
See Emanuel, E., Wendler, D. & Grady, C. (2000) “What makes
clinical research ethical?” JAMA, 283, 2701 – 2711
What makes research ethical?
6. Informed consent cont’d
Generally, informed consent has a number
of components
1. Disclosure of information
2. Comprehension or understanding
3. Voluntariness or freedom
4. Explicit formal consent
In HIV vaccine trials, consent is also staged
(screening, enrolment and HIV testing).
What makes research ethical?
6. Informed consent cont’d
• 1. Information
• Participants must be informed of the following:
– Aims, purpose, duration
– Methods (e.g. randomization, placebo, blinding)
– Practical aspects (VCT, tests, visits, use and
storage of tissue samples, etc.)
– Potential risks (e.g. trial related discrimination)
– Expected benefits (e.g. counselling)
– The right to withdraw
– Compensation for research related injury
– Confidentiality (and limits if any)
– Personal implications.
What makes research ethical?
6. Informed consent cont’d
• Complexities:Transmission of complex
information, compounded by language
differences, translation.
• Information transmission typically viewed as a
one way process, whereas it is best
conceptualized as bi-directional, where
researchers & counsellors make every effort
to hear the expectations & motivations of
potential participants.
• Determinations of “what” must be transmitted
is governed by disclosure requirements, but
should also be supplemented by
recommendations from community
representatives & constantly assessed.
What makes research ethical?
6. Informed consent cont’d
• 2. Comprehension
• Disclosure is not sufficient and participants’
comprehension must be ensured and assessed.
• Complexities:
• Social desirability: Tendency to act to avoid
disapproval that impacts on reported
understanding.
• Overemphasis on understanding of technical
aspects (e.g. placebo) & less on understanding of
implications for a participant’s personal and social
life.
• “Tests of understanding” may emphasize technical
aspects and assess short-term memory and not
actual understanding of the personal
consequences.
What makes research ethical?
6. Informed consent cont’d
• Researchers and counsellors can enhance
comprehension by:
– Creating an optimal environment for decision
making (vs. “consent counselling”)
– Ensuring use of counsellors with “values
match” to potential participants
– Encouraging dialogue; discussion with family
– Allowing time to reflect
– Sensitivity to process aspects of counselling
(e.g. social desirability, non-verbal cues)
– Multiple methods of assessing
comprehension.
What makes research ethical?
6. Informed consent cont’d
• 3. Voluntariness
• Participants must be free to choose whether
or not to participate, free of coercion (threat of
negative sanction) or undue influence to
participate (excessive incentives  pressure
to volunteer against better judgement).
• Special care must be taken with participants
who are considered vulnerable and therefore
constrained in their ability to make free
choices.
"...John Rawls, perhaps the leading moral philosopher
of our time, has argued that all human beings are
endowed with moral capacities. He is right to insist on
this, but the deployment of those capacities are
severely constrained by the epistemic difficulty in
grasping what exactly is happening and how things
could be actually different. The lessons of the tsunami
and the global response it has generated not only
include the affirmation of the ethical capacity of people
in general, sometimes even at great distance, but also
the critical importance of communication and
understanding. The connection between epistemology
and ethics can be very powerful, and this is part of the
interdependence of the world in which we
live. Ignorance and incomprehension are enemies not
only of science, but also of the practice of ethics..."