Ethics of research with human volunteers and the College Ethics Review Board

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Ethics of research with human volunteers and the
College Ethics Review Board

• Justin H G Williams
• University of Aberdeen

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History

• Late 19th century trials being carried out on
  hospital patients
• E.g.transplant of tumour tissue from one patient
  to another
• Albert Neisser (a Jew) went into dermatology
  discovered gonococci and Neisser stain.
• Developed cell-free serum to use as vaccine
  against syphilis
• 1892 Administered it to young women prostitutes
  in hospital

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• Some of the women developed syphilis.
• Neisser blamed patients occupation
  (prostitution) and concluded his serum to be
  ineffective but harmless.
• Media accused him of giving syphilis to children
  and destroying their lives
• Much debate in Prussian parliament
• Found to have harmed patients and was fined.
• Judgement and politics very much influenced by
  anti-semitic, anti-immunization creeds amongst
  professionals and the media.

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• Prussian parliament issued the first directive
  governing medical research, stating that all
  research should require
• A competent subject
• Explicit consent
• A proper explanation of the possible negative
  consequences
• 1920s Criticism of medical research in
  collaboration with creative chemical industry
  (soon to produce sulphonamides)
• 1931 Reich issued guidelines
• 1946 Nuremburg issued code good for Barbarians
  but unnecessary for ordinary doctor-scientists
• WMA agreed Declaration of Helsinki in 1964
• Not binding in UK

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• 1967 Royal College of Physicians advises that a
  group of doctors should supervise the ethics of
  research
• BMA argue for self-autonomy and remain sceptical
• Further report from RCP in 1973
• RECs developed
• 1990 first National Training Conference in
  Swansea
• 1991 Local Research Ethics Committees
• 1997 Multi-centre Research Ethics Committees
• 2001 GAfREC
• 2003 EC directive

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Context 1

• Governance insurance, resources management (NHS
  or University RD)
• Legality e.g. Data protection, human tissue act,
  radiation protection,
• Other regulation e.g. MHRA,
• Good science peer review by funding agency or
  colleagues
• The primary job of the ethics committee is to ask
  if research is ethical not if it is legal.

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Context 2

• An ethical obligation to do good science
• If you do not know you need to find out!
• Vulnerable populations have an equal right to
  research that will benefit them e.g. prisoners,
  elderly, children and learning disabled.
• Mutual trust between committee and scientist is
  necessary
• Need to assume best motive on either side.
• Ethics committee should act as a critical friend
• Strict rules on conflicts of interest a need to
  be open and transparent
• Not a matter of getting it past the ethics
  committee.

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Ethics is about

• Validity
• Safety
• Dignity

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Validity

• Is this research or audit?
• Research is a venture designed to obtain new
  knowledge that is generalisable.
• Is this a genuine question to which we really do
  not know the answer?
• Invalid science is not ethical (Where there is an
  educational objective? )
• Equipoise in trials 2 balanced arms where you
  really do not know which arm is preferable.
  Therefore randomisation is the only ethical
  choice.
• Is it statistically sound? Is an expert required?

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Safety

• Minimal risk must be achieved.
• Is there any danger to participants?
• Are procedures being carried out correctly?
• Are researchers adequately trained?
• Are facilities well managed and safe?
• Does the sponsor have adequate insurance?

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Dignity

• Are patients needs and rights being respected?
• Consent a) to be screened b) to take part
• Confidentiality
• Human beings not human guinea pigs
• Are they from vulnerable groups?
• Do they require renumeration?
• Do they require follow-up?
• ? Compensation? Insurance?

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Consent

• By definition it is informed
• Do your volunteers have the capacity?
• To make a free decision after weighing up the
  advantages and disadvantages
• Been provided with the information?
• Do they comprehend the information?
• Do they remember it?
• Can they weigh it up?
• Can they communicate their intention?
• Consent vs assent

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How much information should you provide?

• Patient must be informed of material risk
• What amounts to material risk? Shifting sands
• 1957 what other practitioners would do in that
  position
• 1985 what the reasonable doctor should do
• 1999 what the reasonable patient should expect
• 2004 what the reasonable patient should expect
  in light of their situation and circumstances.
• Reflects increasing respect for autonomy and
  dignity of patients

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Consent (contd)

• The consent form only provides evidence of
  consent
• Patient needs to have been given the information
  and understood it.
• Information sheet should contain as much
  information as possible about risks that the
  participant can understand.
• Exception information may not be given if it
  would be therapeutically disadvantageous to do so
  (but only a let out clause to be used very
  carefully)

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Providing Information

• Who is your audience?
• Young, old, learning disabled?
• Normal IQ? Reading Age?
• Comprehensive vs comprehendable
• Your volunteers do not have all day!
• Consider getting help from your secretary.

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Providing information (contd)

• What is going to happen?
• What are the benefits (self and others)?
• What will be required of me?
• What are the possible risks, costs, benefits?
• Anticipate and allay anxieties (if appropriate)

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Providing information contd

• Be truthful but do not create anxiety
• Anticipate and allay anxieties (if appropriate)
• Provide an appropriate amount of information for
  the demands of the experiment.
• Consider pictures and other aids to comprehension

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What does he or she need to know?

• What is going to happen in the experiment?
• What are the benefits
• For the population in general
• For me personally

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Problems with the discovery of unwanted
information

• Growing problem in neuroimaging and genetic
  studies on healthy people.
• Problems on brain scans and genetic
  susceptibilities
• Responses on questionnaires
• Do you tell the patient?
• Need to prepare for unexpected findings
• Volunteer needs to be prepared beforehand
• Should you systematically look for abnormalities?

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Insurance

• Genetic Insurance Advisory Committee
• Diagnosis of Huntingtons may be used to load
  premiums
• No other tests are currently used
• British Insurers have stated that they will not
  use the results of research to load premiums

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Rewards and coercion

• Should people be paid for participating?
• When does payment mean the decision to
  participate is no longer free? Could the payment
  be considered coercive?
• Means of payment
• Reimbursed expenses
• Tokens of thanks
• Small salary (5/hr)
• (free medical treatment in the U.S.)

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Payment (contd)

• Reflects inconvenience and disruption.
• Also reflects discomfort (e.g. due to pain or
  collecting samples)
• Payment should not be paid for perceived risk.
• Do not state what payment is in advertisement

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http//www.abdn.ac.uk/clsm/staff/cerb/
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Summary

• Validity, Safety, Dignity
• Ethical obligation to do good, productive
  research as well as to prevent harm
• Occurs in a context of societal values, legal
  frameworks, research governance and peer review
• Thank you for your attention. Justin.williams_at_ab
  dn.ac.uk