Consent in acute stroke trials: a view from IST3 Peter Sandercock University of Edinburgh SRN Training Day Newcastle 25 th June 2008

Outline Outline of the trial Process of developing the consent materials Training slide set Study of method of consent in first 300 patients recruited

Thrombolysis for stroke Thrombolytic treatment with rt-PA is now approved for selected patients with acute ischaemic stroke < 3hrs of onset. Trial question: ‘can a wider variety of patients benefit that do not exactly meet the strict criteria of the current licence?’ IST-3 is a multicentre, randomised, controlled trial of rt-PA in patients who present with acute ischaemic stroke < 6 hours after symptom onset (target 3100 patients by 2011).

IST-3 trial: randomisation If patient fits main eligibility/exclusion criteria, Clinician/patient/family discuss. If: Clear INDICATION FOR rt-PA  TREAT (i.e. meets terms of current licence and patient agrees) Clear CONTRAINDICATION TO rt-PA  DON’T TREAT rt-PA ‘PROMISING BUT UNPROVEN’  RANDOMISE

Methods to develop consent process for IST-3 A. Meetings with groups of older people Participants completed a questionnaire on thrombolysis B. Focus groups about thrombolysis Meetings were directed by RL and LK Recorded, transcribed and analysed Common themes identified C. Stroke patients and carers consulted Stroke rehabilitation ward Koops & Lindley BMJ 2002;325;415-

Focus groups Volunteers from Morningside branch of the Scottish Old Aged Pensions Association Bingham and District Older Peoples’ Project

Outcome of the focus groups 54 people attended the meetings. Nearly all would accept treatment in routine practice if it was shown to be effective. Four (9%) participants considered the risks of thrombolysis too great, Most (89%) were prepared to accept the treatment in a clinical trial. Most (85%) would give their consent to enter the planned trial. Koops & Lindley BMJ 2002;325;415-

Development of patient information leaflet & consent process for IST3 Draft information material -> readability check Draft discussed at focus groups Themes incorporated in re-draft Re-draft -> patients and carers on stroke unit Readability checked and maximised* –Front A4 page: bullet point ‘script’ –Additional information in more detail on subsequent pp. Submitted for ethical approval – easily approved Slide training set for investigators prepared Koops & Lindley BMJ 2002;325;415- *Flesch Reading Ease 70.7 (easiest = 100) Flesch-Kincaid Grade Level 7.2 (Tabloid level)

Training slide set

Consent needs to be humane, appropriate and adapted to individual circumstances Less can be more Most consent procedures involve person responsible and not the patient Bring accompanying relatives with you from A&E DO NOT let the relatives go until all consent issues are resolved There is less uncertainty if you discuss the trial after the CT brain scan Let the relatives read the information leaflet before the scan Use the bullet points on the front sheet of the leaflet as your ‘script’

1 You have had a stroke This stroke is due to a blood clot in the brain that looks after {insert current impairments of patient here!} The best management for this type of stroke is the stroke unit which has been shown to increase your chances of becoming independent

2 Unfortunately, we do not have particularly effective tablets or injections for this sort of stroke Aspirin works but only has small benefit We are interested in finding better treatments for your sort of stroke and we are discussing this with you now as we are running a study, a clinical trial of a treatment called rt-PA.

3 The treatment is called rt-PA and can dissolve the blood clot that has caused your stroke This treatment is already known to work for some patients {and now is the time to explain why they missed out, too late, too old, too big a stroke, too mild}

4: The main pros and cons of treatment Previous studies have suggested that more people {like Patient X} may get better with rt- PA. Better recovery is expected in about 10% of people, or about a 1 in 10 chance. However, rt-PA can sometimes cause bleeding in the brain, which could make the stroke worse. Bleeding in the brain can sometimes be fatal. This occurs in about 4% of people, about a 1 in 25 chance. Skin bruising, other bleeds and allergies

5: The choices in the trial If you give permission to join the trial, you may or may not receive rt-PA. This type of study is called a ‘randomised controlled trial’. {I often add ‘we don’t know, for people like you, if it is better to give the drug or to avoid it’} I don’t choose the treatment, this is done by random allocation by the study computer.

Summary: The choices You will have a 50% chance of receiving either our usual current medical treatment of aspirin Or A 50% chance of receiving the injection and intravenous infusion of rt-PA, to be followed by aspirin once the second brain scan check has been completed tomorrow. And of course, you’ll receive our usual management in the stroke unit which has been shown to improve your chances of recovery

Administrative details If you give permission for the study we will collect some details about you, and complete a study form in a week’s time. We will then check how you get on with a questionnaire in 6 months time and annually thereafter. We will check important details with your own doctor

Questions and confirming consent Have you any questions? To confirm your consent I need to get you to sign this form (which I’ve also signed) and we will get staff nurse here to witness that you’ve had an opportunity to ask any questions. You, of course, have the right to decline this invitation at any time without this affecting your medical care

Immediate feedback and documentation Record all consent procedures in the medical record Put a copy of the consent form in the patients notes Keep the original consent form in your investigator site file Once randomised, tell the patient and relatives the treatment allocation and the plans for the next few hours and days

Consolidate the consent process by including it your subsequent ward rounds “Thank you for helping us with our research” “You will be having the second brain scan today as part of the IST-3 study you are helping us with” “The scan shows that you tolerated the rt-PA very well”

Methods of consent Written by patient, if able to understand and write Verbal if can comprehend, but unable to write Assent (now consent) by relatives, if patient is mentally incompetent as a result of the stroke Waiver under strict criteria, may be permitted by some local ethics committees Data from first 300 patients randomised

Method of consent in first 300 Assent by a relative: 197 (66%) Written consent: 71 (24%) Witnessed verbal consent: 30 (10%) Waiver of consent: 2 (1%)

Summary The information leaflet was much improved by the input from consumers and rapidly approved by ethics committees. In the first 300 patients randomised: –Assent by relative was the most common form of consent –Of those where assent was used, 2/3 had severe strokes –A small proportion of (12%) patients with TACI were able to give written or witnessed verbal consent. Conclusion: a variety of appropriate forms of informed consent are available for use in IST-3, which can be adapted to local circumstances and used flexibly

Consent: dilemmas Informed consent important both in clinical practice as well as trials Deficit has to be severe enough to justify the risks. If deficit mild: –“If the patient is capable of giving consent then the stroke is not severe enough to justify treatment” If deficit severe & patient incompetent to consent: –If onset < 3hrs, is it ethical to treat without consent? –It is unethical to include patients who are not competent to give informed consent in a randomised controlled trial when the treatment risks are not “minimal in relation to the standard treatment available”