Sheffield April2008

Research ethics committees & the law

John SaundersHon professor, Centre for Philosophy, Humanities & Law, School of Health Science, University of Wales Swansea; chair, Committee for Ethical Issues in Medicine, Royal

College of Physicians of London

Sheffield April2008

What is law?• “beyond the

specific issues that arise in relation to the practicalities of recognition or delegation, there are large questions in the background about what we understand by and expect from the law”

Rowan Williams (at Royal Courts of Justice, 7/2/08)

Sheffield April2008

• Legal basis for RECs

• Indemnity and the REC

• Legal opinion & the REC

Sheffield April2008

1. Legal basis

• Initially none

• 1968 Circular HM(68)33; 1975 HSC(IS)153;1991 HSG(91)5; 1997 HSG(97)23

• SI 2004/1031 (Medicines for Human Use (clinical trials) Regulations)

• UK Ethics Committee Authority ‘recognise’

Sheffield April2008

The EC Clinical Trials Directive (2001/20/EC)

• Establishes certain standards e.g. single opinion, 60 day rule

• Refers to GCP

• ECGCP Directive 2005/28/EC

• ICH GCP (4.8.1): “should adhere to the ethical principles….in the Declaration of Helsinki”

• Is that Declaration legally binding?

Sheffield April2008

Legal basis (2)

Other statutory obligations include:

• Human Tissue Act 2004 – REC approval needed for research (with minor exceptions)

• Mental Capacity Act – permits non drug research if REC approved

• Hence, statutory basis for CTIMPs, tissues, mental incapacity

Sheffield April2008

Human tissue Act: legal obligations for the REC

• Distinguish between licensing and ethical review• Where tissue is from a living person for

treatment, no licence for research, but REC must approve

• If tissue distributed to others (e.g. tissue bank) or for future project, licence needed; but not if for a specific project. REC must approve UNLESS band has REC approval AND tissue anonymous to researcher.

Sheffield April2008

Human tissue Act: legal obligations for the REC (2)

• If tissue removed from the dead, license and REC approval always needed

• Human Tissue (Scotland) Act 2006 does not cover tissue from living (exc Tx)

• Consent can be “broad & durable” or “limited in time and scope”

• Consent not essential for anonymised studies from the living (e.g. national tonsil archive).

Sheffield April2008

Legal basis (3)

• Human Rights Act 1998:

• A public authority is a body to included ‘any person certain of whose functions are functions of a public nature’ - & hence the REC?

• Unlawful for a public body to act in a way incompatible with Convention rights (e.g. article 3: inhuman treatment etc.)

Sheffield April2008

Legal basis (4)

• REC not a legally constituted body

• Duties of the REC are individual duties

• Members liable individually

• RECs don’t authorise research, but advise

• Advisory role does not exempt liability

• No definition of reasonable care of REC member

Sheffield April2008

Legal basis (5)

• “the appointing authority will take full responsibility for all the actions of a member….other than those involving bad faith, wilful default or gross negligence.”

• Possibility of judicial review actions e.g. for acting outside terms of reference.

Sheffield April2008

Legal basis (5)

• But………….no REC member has ever been subject to legal action

Sheffield April2008

Indemnity & the REC (1)

• Not specified in the EC Directive

• Non-negligent injury must be covered in healthy volunteer studies (Medicines Commission)

• Under Research Governance Framework, trial sponsor is responsible for an agreement about provision & financial arrangements (not REC)

Sheffield April2008

Indemnity & the REC (2)

• Non-negligent injury: the ABPI Clinical Trial Compensation Guidelines

• Provided without legal commitment

• Based on balance of probabilities

• Phase 2 & 3 trials (separate guidance for phase 1)

• Injury of disabling or injurious character

Sheffield April2008

Indemnity & the REC (3)

• MRC will give ‘sympathetic consideration’ to an ex gratia payment for non-negligent harm

• No arrangements for NHS

• GPs are independent contractors & must make own arrangements (guidance from NRES)

Sheffield April2008

Indemnity & the NHS

• “a serious injustice to patient research subjects” (Evans & Evans, 1996)

• Not specified in guidelines

• RECs should ensure that patients are advised on what the arrangements are (i.e. you have cover for negligent injury only in the case of NHS trials)

Sheffield April2008

Indemnity & the NHS (2)

• NHS does not offer non-negligent indemnity for treatment (etc), nor does it take out external insurance.

• Is research different, as Evans & Evans suggest?

Sheffield April2008

equipoise

• If comparing A and B, the two arms of the study must be equally balanced (equi-poise)

• i.e. although the new investigation or treatment (A) may be better than the old one (B), we do not know this: A may have unforseen hazards

• There is genuine uncertainty between A & B

Sheffield April2008

Equipoise =

Every patient entered could ethically be given any of the treatments (etc) in the trial

Sheffield April2008

The implication of equipoise

• If no-one knows which treatment or procedure or test is best, the rational doctor must advise the rational patient to choose the treatment (etc) by chance (= at random)

• Randomisation is the best method for making choice under uncertainty

Sheffield April2008

False beliefs:

• Trials are run to benefit future patients at the expense of present ones.

• Excluding patients from trials deprives them of benefits.

Rather:• Trial=choice under uncertainty + data

collection. Randomisation is the best method for making choice under uncertainty

Sheffield April2008

Indemnity: the implication of equipoise

• The patient receives the best current available treatment: ‘the rights, safety & well being’ are protected

• The interests of society do not prevail over that of individuals

• Forseeable risks have been weighed against anticipated benefit (EC Directive)

Sheffield April2008

Minimal risk

• In non-therapeutic studies

• Where this enables smaller numbers of subjects and the possibility of clearer answers

• And in therapeutic studies where extra measurements etc needed

• Defined: a slight & temporary negative impact on health (Council of Europe)

Sheffield April2008

“component analysis” (Weijer & Miller. Nature Medicine  10, 570 - 573 (2004)

Sheffield April2008

Minimal risk: a question

• Should an individual be offered indemnity for non-negligent injury for an altruistic act that offers no benefit to the individual?

• Would you want a legal guarantee of indemnity if you altruistically went to get your neighbour’s newspaper in case you tripped and injured yourself?

Sheffield April2008

Indemnity & the REC

• Article 6 of EC Directive:

• “In preparing its opinion the Ethics Committee shall consider…(h) provision for indemnity or compensation in the event of injury or death attributable to a clinical trial”

Sheffield April2008

Legal opinion & the REC

Research Governance for Health & Social Care, 2nd edition, 2005, Section 3.12.7:

 It is not the responsibility of research ethics committees described above to give legal advice, nor are they liable for any of their decisions in this respect. Irrespective of a decision of a research ethics committee on a particular application, it is the researcher and the NHS or social care organisation who have the responsibility not to break the law. If a research ethics committee is of the opinion that implementation of a research proposal might contravene the law, it should advise both researcher and the appropriate authority of its concerns. The researcher and the organisation will need then to seek legal advice.

Sheffield April2008

The RCP guidelines

• “RECs should avoid expressing a legal opinion and a proposal should not be given an unfavourable opinion on the grounds of its supposed illegality. Should a committee believe that a proposal contravenes the law, it should ask the principal investigator to seek further advice.”

Sheffield April2008

Does this guidance fit with the EC Directive?

• Regulations (SI2004/1031) implementing the EC Directive, Schedule 1,pt 2 states that the ‘rights, safety & well being of subjects are the most important consideration’.

• The Research Governance Framework specifies this (3.12.2) as REC responsibility (among others)

Sheffield April2008

REC responsibilities - how?

• ‘Rights’ (etc) are not an exclusive REC function to protect

• ‘Rights’ implies legal rights?• But even if the REC has a role to protect

legal rights (implicitly to be confident that research is lawful), it does not follow that it must assess that, only that it is confident that this responsibility is addressed.

• (Similarly, quality of facilities etc)

Sheffield April2008

Conceptual reasons for this

• Unlawful activity may be unethical

• Lawful activity may be ethical

• BUT

• It is not just because they are lawful that they are ethical (etc)

• RECs are to advise on ethics and therefore must ignore legal judgements

Sheffield April2008

Possible consequences

• The REC could approve something that it thought might be unlawful

• But it must advise PI to seek legal advice

• Correspondence goes to sponsor (etc)

• Those responsible for ensuring legality are informed

• No possibility of patient harm

Sheffield April2008

An example

• EC Directive & emergency research

• No provision for lack of legal representative in emergency research

• SI 2006/2984 was needed to put this right two years after the Directive

Sheffield April2008

RECs and legal opinion

In practice:

• Not constituted to give it

• Unnecessary delays may result(e.g. NZ cervical cancer audit)

Sheffield April2008

In summary

• RECs now have a legal basis

• Indemnity arrangements vary & RECs should clarify what they are, ensuring participants understand

• Legal judgements should be avoided.