title: Which factors influence the resort to surrogate consent in stroke trials, and what are the patient outcomes in this context?
abstract: BACKGROUND
  The provision of informed consent is a prerequisite for inclusion of a patient in a clinical research project. In some countries, the legislation on clinical research authorizes a third person to provide informed consent if the patient is unable to do so directly (i.e. surrogate consent). This is the case during acute stroke, when the symptoms may prevent the patient from providing informed consent and thus require a third party to be approached. Identification of factors associated with the medical team's decision to resort to surrogate consent may (i) help the care team during the inclusion process and (ii) enable the patient's family circle to be better informed (and thus feel less guilty) about providing surrogate consent.
  
  
  METHODS
  Patients included in the BIOSTROKE cohort (initially dedicated to the analysis of factors influencing stroke severity) were divided into two groups: those having provided informed consent directly and those for whom a third party (such as a family member) had provided surrogate consent. We compared the groups in terms of the initial clinical characteristics (age, gender, type of stroke, severity on the National Institutes of Health Stroke Scale (NIHSS), pre-stroke cognitive status according to the Informant Questionnaire on Cognitive Decline in the Elderly, and the stroke's aetiology) and the functional and cognitive impairments (according to the NIHSS, the modified Rankin score (mRS) and the Mini Mental State Examination) on post-stroke days 8 and 90.
  
  
  RESULTS
  Three hundred and ninety five patients were included (mean ± SD age: 67 ± 15 years; 53% males). Surrogate consent had been obtained in 228 cases, and 167 patients had provided consent themselves. The patients included with surrogate consent were likely to be older and more aphasic, with a pre-existing cognitive disorder and more severe stroke (relative to the patients having provided consent). In terms of recovery, the patients included with surrogate consent had a worse functional prognosis (day 90 mRS ≥3: 57.6%, compared with 16.8% in patients having provided consent themselves; p < 0.0001) and a worse cognitive prognosis (day 90 MMS < 24: 15.4% and 4.8%, respectively; p < 0.002). The mortality rate was significantly higher in the surrogate consent group.
  
  
  CONCLUSIONS
  We found that in addition to age, aphasia and stroke severity, pre-stroke cognitive status is a factor that should prompt the care team to consider requesting surrogate consent for participation in a clinical study. Given that the unfavourable outcome in patients with surrogate consent is often due to their initial clinical state (rather than inclusion in a trial per se), the issue of the family's feelings of guilt (and how to avoid these feelings) should be further addressed.
authors.affiliation: U1171-Department of Neurology, University of Lille, Inserm, Faculty of Medicine, Lille University Hospital, Lille, France. anne-marie.bordet@chru-lille.fr.|Clinical Research Federation, University of Lille, Lille University Hospital, Lille, France. anne-marie.bordet@chru-lille.fr.
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Mendyk
authors.affiliation: EA2694-Department of Statistics, University of Lille, Faculty of Medicine, Lille University Hospital, Lille, France. julien.labreuche.chru@gmail.com.
authors.forename: Julien
authors.initials: J
authors.lastname: Labreuche
authors.affiliation: U1171-Department of Neurology, University of Lille, Inserm, Faculty of Medicine, Lille University Hospital, Lille, France. hilde.henon@chru-lille.fr.
authors.forename: Hilde
authors.initials: H
authors.lastname: Henon
authors.affiliation: Department of Emergency, Lille University Hospital, Lille, France. marie.girot@chru-lille.fr.
authors.forename: Marie
authors.initials: M
authors.lastname: Girot
authors.affiliation: U1171-Department of Neurology, University of Lille, Inserm, Faculty of Medicine, Lille University Hospital, Lille, France. charlotte.cordonnier@chru-lille.fr.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Cordonnier
authors.affiliation: EA2694-Department of Statistics, University of Lille, Faculty of Medicine, Lille University Hospital, Lille, France. alain.duhamel@univ-lille2.fr.
authors.forename: Alain
authors.initials: A
authors.lastname: Duhamel
authors.affiliation: U1171-Department of Neurology, University of Lille, Inserm, Faculty of Medicine, Lille University Hospital, Lille, France. didier.leys@univ-lille2.fr.
authors.forename: Didier
authors.initials: D
authors.lastname: Leys
authors.affiliation: U1171-Department of Pharmacology, University of Lille, Inserm, Faculty of Medicine, Lille University Hospital, 1 place de Verdun, Lille cedex, F-59045, France. regis.bordet@univ-lille2.fr.
authors.forename: Régis
authors.initials: R
authors.lastname: Bordet
mesh_terms: D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D001037:Aphasia; D035843:Biomedical Research / Q000941:ethics; D003071:Cognition; D003072:Cognition Disorders; D003657:Decision Making; D005260:Female; D006801:Humans; D007258:Informed Consent; D008297:Male; D008875:Middle Aged; D018579:Patient Selection / Q000941:ethics; D019727:Proxy; D012107:Research Design; D035842:Research Subjects; D012720:Severity of Illness Index; D020521:Stroke; D014481:United States