Transcript Acute Stroke

Consent in acute stroke
trials: a view from IST3
Peter Sandercock
University of Edinburgh
SRN Training Day
Newcastle 25th 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
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•
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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
*Flesch Reading Ease 70.7 (easiest = 100)
Flesch-Kincaid Grade Level 7.2 (Tabloid level)
Koops & Lindley BMJ 2002;325;415-
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 rtPA. 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”