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

Ethics of research with human volunteers and the College Ethics Review Board Justin H G Williams University of Aberdeen

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

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.

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 • 1920’s 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

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 • REC’s developed • 1990: first National Training Conference in Swansea • 1991 Local Research Ethics Committees • 1997 Multi-centre Research Ethics Committees • 2001 GAfREC • 2003: EC directive

Context 1 • Governance – insurance, resources management (NHS or University R&D) • 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.

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.

Ethics is about: Validity Safety Dignity

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?

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?

Dignity • Are patient’s 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?

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

How much information should you provide? Patient must be informed of “material risk” What amounts to material risk? Shifting sands: • 1957: what other practitioner’s 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

Consent (cont’d) • 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)

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.

Providing information (cont’d) • 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)

Providing information cont’d • 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

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

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?

Insurance • Genetic Insurance Advisory Committee • Diagnosis of Huntington’s 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

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.)

Payment (cont’d) • 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

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

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@abdn.ac.uk

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