Thrombolysis for acute ischaemic stroke
Authors: H. Mann
Journal: BMJ (2002)

Editor—Koops and Lindley involved consumers in the design of a randomised trial of thrombolysis in acute stroke and published the associated patient information sheet.1,2 Critical appraisal of trial information leaflets benefits the manner in which they are conceived and formulated.

In addition to a limited number of eligibility criteria, the trial notably uses the uncertainty principle for determining eligibility of patients.3 The multicentre research ethics committee requested an explanation of this principle in lay language in the information sheet: Your doctor believes that there is no proof that rt-PA will definitely help you. If your doctor was convinced that you should be given the new treatment (for whatever reason) you would have been given it. If your doctor believed that you should definitely avoid rt-PA treatment, you will not receive it and you would not be invited to join this sort of study. Having weighed up the pros and cons of treatment your doctor feels there is “an absence of proof” for rt-PA for your particular circumstances. You are therefore eligible for the trial.

Uncertainty may be present at three levels: the community of “expert” practitioners (also relevant to research ethics committees that must approve the trial); the patient's doctor (who has to decide whether to participate in the trial and then offer enrolment to particular patients); and the patient (who has to decide whether to enrol).4 The language above clearly addresses the doctor's uncertainty, but it does not adequately clarify that the ultimate decision is the patient's or provide any guidance pertinent to that decision.

Trial participation is a rational choice when an adequately informed patient is maximally uncertain—in equipoise—as to the relative efficacy and safety of comparator interventions. The patient also needs to be in equipoise about any other interventions available outside the trial, including the possibility of participating in another relevant trial. As Lilford has described, the concept of patient equipoise may be understood in the context of utility theory.5 Provision of the necessary information, and a discussion of this decision strategy, should be a part of the consent process. The challenge, of course, is to accomplish this in a manner comprehensible to potential participants.

Language such as the following may be considered for such a trial: The trial's investigators believe patients like you may benefit from rt-PA. Because this is not yet known for sure, this trial is being run with a large number of participants. Because of this uncertainty, your doctor believes participation is a reasonable option for you. If, after discussing the potential benefits and harms of rt-PA, and other alternatives, with your doctor, you are also completely uncertain, joining the trial is a good option. This is called the uncertainty principle, and it helps doctors and patients decide what to do about clinical trials. Also, for a patient, deciding to be randomised in this situation gives one the best odds (50%) of getting the preferred treatment, no matter which one is subsequently shown to be better, on average, after the trial is completed and the results analysed.