Impact of Stroke Syndrome and Stroke Severity on the Process of Consent in the Third International Stroke Trial

Abstract

Background: Obtaining informed consent for a patient’s participation in a randomized trial of treatment for use in a medical emergency may be achieved in a variety of ways. We sought to assess the process of consent and to evaluate the influence of the patient’s neurological deficit on the method used to obtain consent in the first 300 patients recruited into the Third International Stroke Trial (IST-3). Methods: IST-3 is the first large-scale randomized controlled trial of intravenous thrombolysis in acute ischaemic stroke. The clinician could use one of four procedures to recruit the patient: written consent, witnessed consent, assent, or a waiver of consent. The patient’s neurological deficits were recorded at baseline. We analysed the relationship between the neurological deficits at baseline and the consent procedure. Results: The method of consent used was written consent in 71 subjects (24%), witnessed verbal consent in 30 subjects (10%), assent by a relative in 197 subjects (66%), and waiver of consent in 2 subjects (1%). Patients with severe neurological deficits (as measured either by their stroke syndrome or their lower predicted probability of being alive and independent at 6 months) were more likely to be recruited by assent. Patients able to give written consent had less severe strokes. Conclusions: Patients with non-lacunar hemispheric stroke syndromes or with a more severe neurological deficit were less likely to give written consent. Excluding such patients from acute stroke treatment trials would eliminate many otherwise eligible subjects, who have a poor predicted outcome without treatment and yet might benefit from acute treatments such as thrombolysis. Flexible consent procedures developed for IST-3 have made it feasible to recruit the target population.

Impact of Selection Criteria on Recruitment in an Interventional Stroke Trial

“…As expected, aphasia was more frequently the reason for excluding patients suffering from MCA strokes with an NIHSS score of ≥4 (table 3). This is in line with previously published data on ability to consent and its correlation with infarct volume and neurological deficits [3,10]. …”

Brain Lesion Volume and Capacity for Consent in Stroke Trials

“…Demarquay and colleagues 4 showed that capacity diminishes with increasing age and baseline neurological deficit. Similarly, data from the first 300 patients recruited to the third International Stroke Trial (IST3) 5 show that those with more severe stroke were less likely to have been recruited by consent, with clinical syndrome being an important determinant.…”

Effect of waivers of consent on recruitment in acute stroke trials

“…Secondary analyses of 2 large stroke trials indicate that most patients in those trials were enrolled via surrogate consent and that limiting trials to patients able to consent for themselves would have restricted the generalizability of these studies by excluding patients with more severe strokes. 12,13 It is unclear whether other alternatives to written informed consent, such as waivers or verbal consent, would also materially affect the feasibility and generalizability of acute stroke trials. We conducted a systematic review of acute stroke trials to assess whether the specific methods of obtaining informed consent are associated with the participant recruitment rate in these trials.…”

“…This in part reflects inherent difficulties of data collection under the intense time pressure of acute stroke care. In earlier studies of the impact of surrogate consent on recruitment and generalizability, 12,13 data from individual trials about the number of participants enrolled via surrogate consent as compared with self-consent were useful in establishing the importance of surrogate consent. Closer examination of variation within trials allowing waivers of informed consent may provide valuable insights into the effects of such waivers on recruitment.…”