Ethics from fundamentals to justice

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Ethics from fundamentals to justice fair-play

• Sisira Siribaddana
• Forum for Research Development

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Introduction to bio ethics(this section is
adapted from slides by Doug Wassener)
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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

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What is the role of ethics in research? contd

• 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

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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

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What are the key principles in research ethics
contd?

• RESPECT FOR AUTONOMY self-rule
• A persons 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

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What are the key principles in research ethics
contd?

• 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

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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

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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.

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Community participation contd

• 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).

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Community participation contd

• 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)

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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

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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.

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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).

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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.

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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

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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.

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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).

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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.

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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.

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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)

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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)

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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 arms length).
• But RECs should be competent and confident to
  review complex designs.

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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).

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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

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What makes research ethical?6. Informed consent
contd

• 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).

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What makes research ethical?6. Informed consent
contd

• 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.

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What makes research ethical?6. Informed consent
contd

• ComplexitiesTransmission 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.

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What makes research ethical?6. Informed consent
contd

• 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 participants personal and
  social life.
• Tests of understanding may emphasize technical
  aspects and assess short-term memory and not
  actual understanding of the personal consequences.

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What makes research ethical?6. Informed consent
contd

• 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.

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What makes research ethical?6. Informed consent
contd

• 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.

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"...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..."