Informed consent in emergency research – a contradiction in terms

Dr Malcolm G BoothDept. of Anaesthesia

Glasgow Royal InfirmaryScotland

Informed consent in emergency research – a contradiction in

terms

• Basis of informed consent for therapy• Difference between consent for therapy

and research• Options for consent in emergency research• Options for the future of emergency

research

Consent for therapy

• 4 principles of medical ethics:–Non-maleficence–Beneficence–Autonomy– Justice

Autonomy

• Self determination• Make informed choices• Decide tolerable risk / benefit ratio• Decide to accept or forego therapy • Accept the risk of so doing

Consent for research

• Nuremberg Code– Reaction to 1939-45 war– Often ignored (Beecher NEJM 1966, Pappworth

1967)

• Declaration of Helsinki (revised 2000)– All subjects to freely, and without duress, give

their consent to participate

- If incompetent then consent from their legal guardian in accordance with national legislation

Consent for “normal” research

• Potential subjects invited to participate

• Information leaflet provided

• >24 hours to decide • Informed consent

obtained• Unethical to recruit

without consent• Helps protect rights,

safety and welfare of participants

Emergency research is different

• No advance invitation• No time to decide• Incapacitated patient• Informed consent not

obtained from participant

• Need minimal delay to treatment

The TROICA Study

International multicentre trial to assess the efficacy and safety of tenecteplase during cardiopulmonary resuscitation in patients with out-of-hospital cardiac arrest: The Thrombolysis in Cardiac Arrest (TROICA) Study

Spohr et al. European J of Clinical Investigation

2005; 35: 315-23

The CRASH Trial

• Effect of intravenous corticosteroids on death within 14 days in 10,088 adults with clinically significant head injury (MRC CRASH Trial): randomised, placebo-controlled trial.

Crash Trail Group

Lancet 2004; 364: 1321-28

Emergency research

• “Normal” consent process cannot apply• Need alternatives to “normal” consent• Need minimise delay to start of treatment• No emergency research

No emergency research

“ A medical profession which did not seek improved means to conquer disease would be condemned for dereliction of duty. Members of the public….justified in expecting the development of more effective therapies for illness…”

Dickens 1979

Alternatives to “normal” consent

• Prospective consent • Deferred consent• Consent from authorised representative

Prospective consent

• Identify ‘at risk’ group• Consent as many ‘at

risk’ as possible in advance

• Hope enough develop emergency condition

Prospective consent - problems

• Need consent enough ‘at risk’?• Truly informed consent? • How to identify those consented?• Alter behaviour?

Need consent enough ‘at risk’?

• Identify ‘at risk’ group• 1% risk of event• Need 100 recruits• Must consent 10 000

Truly informed consent?

• Individual likelihood of participation small

• Risk given due consideration?

• Volunteer when would not otherwise?

Identifying those consented?

• Need to identify those– Consented– Not consented– Refused

Alter behaviour?

• Hawthorne effect: subjects’ behaviour alters because of being observed not because of the intervention

• May make recruiting more difficult• Doll, Peto et al. Mortality in relation to smoking: 40 years’

observations on male British doctors. BMJ, 1994; 309: 901.

Deferred consent

• Accept that consent not possible• Recruit suitable subjects• Get consent later from patient, if recovers,

or from legally authorised representative

Deferred consent - problems

• Cannot consent to something that has already happened!

• How can you refuse if event in the past?• What to do if patient dies or LAR not

available - use data or not?• Will LAR know patients wishes?

Authorised representative consent

• Directive 2001/20/EC– On the approximation of the laws regulations

and administrative provisions of the member states relating to the implementation of good clinical practice on the conduct of clinical trial on medicinal products for human use.

• Adults with Incapacity (Scotland) Act 2000• The Medicines for Human Use (Clinical

Trials) Regulations 2004.

Directive 2001/20/EC

• Article 5: incapacitated adults and research– Informed consent of legal representative– No mention of emergency research

Adults with Incapacity (Scotland) Act 2000

• Proxy consent from relatives• Allowed to consent to research (in advance)• No mention of emergency research

The Medicines for Human Use (Clinical Trials) Regulations 2004.

• Personal Legal Representative– Next of kin– May not be available– May be too distressed to make decision

• Professional Legal Representative– Does not know the patient– Cannot know patient’s wishes– Cannot act on behalf of the patient

Alternatives to ‘normal’ consent

• “Artificial” forms of consent• Political correctness

– must pretend to get consent rather than accept consent impossible to get

• Misleading our patients and ourselves• Unethical

The future of emergency research

• Accept that informed consent not possible

• Emergency research participants have no autonomy to uphold

The future of emergency research

• Treat incapacitated patient as usual• “Best interests” test• “Best interests” may include recruitment to

trial before any consent possible• Waive need for consent

The future of emergency research

• No consentable group• Adequately planned protocol• Ethics committee approval• Informed consent not possible• Consent for continued participation• Intervention intended to benefit subject• Delay not possible

Medical Research in Clinical Emergency Settings in Europe

Lötjönen J Med Ethics2002; 28: 183-187

Research in emergency situations: with or without relatives consent

• 4000 pts, 116 hospitals, 40 countries• 78 ethics committees waived consent• Comparison of time to treatment of those

needing consent and those not• 3.2 hrs v 4.4hrs (p<0.0001)

The CRASH Trial Management GroupEmerg Med J 2004; 21: 703

But what do the public think?

Waiver of Informed Consent: A Survey of Emergency Medicine

Patients

• Emergency department patients: 212• Waiver of consent approved: 73%

– Providing risk minimal

• Risk > minimal: 50%

Smithline and Gerstle. Am J Emergency Medicine

1998; 16: 90-1

Public perception of emergency research

• Self administered questionnaire• Outpatients of university teaching hospital• 362 respondents• Should emergency research be allowed to

start:– Without consent 84%– Consent to continue from relative 81%– Consent to continue from patient 90%

Booth et al. Eur J Anesth2005; 22: 933-37

The way forward

• Informed consent in emergency research NOT possible

• Emergency research needs to continue• Public support for emergency research

The way forward

• No consentable group• Adequately planned protocol• Ethics committee approval• Informed consent not possible• Consent for continued participation• Intervention intended to benefit subject• Delay not possible

Medical Research in Clinical Emergency Settings in Europe

Lötjönen J Med Ethics2002; 28: 183-187

The real way forward

• Presumed consent– As used for organ donation– Would allow advance refusal

Thank you