Brain lesion volume and capacity for consent in stroke trials: potential regulatory barriers to the use of surrogate markers.
OBJECTIVE
European directives and legislation in some countries forbid inclusion of subjects incapable of consent in research if recruitment of patients capable of consent will yield similar results. We compared brain lesion volumes in stroke patients deemed to have capacity to consent with those defined as incapacitated.


METHODS
Data were obtained from 3 trials recruiting patients primarily with cortical stroke syndromes. Patients were recruited within 24 hours of onset and used MRI based selection or outcome criteria. Method of recruitment was recorded with stroke severity, age, and brain lesion volumes on Diffusion Weighted Imaging.


RESULTS
Of the 56 subjects included, 38 (68%) were recruited by assent and 18 (32%) by consent. The assent group had a median lesion volume of 18.35 cubic centimetres (cc) (interquartile range [IQR] 8.27-110.31 cc), compared to 2.79 cc (IQR 1.31-12.33 cc) when patients consented (P=0.0004). Lesions were smaller than 5 cc in 7/38 (18%) in the assent group and 11/18 (61%) in the consent group (P=0.0024). There was good correlation between neurological deficit by NIH stroke scale score and lesion volume (r=0.584, P<0.0001). Logistic regression demonstrated NIHSS or lesion volume predicted capacity to consent.


CONCLUSIONS
Patients with acute stroke who retain capacity to consent have significantly smaller infarct volumes than those incapable of consent, and these are frequently below the limits where measurement error significantly compromises valid use of volumetric end points. Only a small proportion of patients with capacity to consent would be eligible for, and contribute usefully to, most acute stroke trial protocols.
Division of Clinical Neurosciences, University of Glasgow, Institute of Neurological Sciences, Southern General Hospital, Glasgow G51 4TF, Scotland, UK.
Krishna A
KA
Dani
Michael T
MT
McCormick
Keith W
KW
Muir
D000208:Acute Disease; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers; D001921:Brain / Q000473:pathology; D002986:Clinical Trials as Topic / Q000941:ethics*; D038524:Diffusion Magnetic Resonance Imaging; D005060:Europe; D005260:Female; D006801:Humans; D007258:Informed Consent / Q000941:ethics* / Q000592:standards; D016015:Logistic Models; D008297:Male; D011237:Predictive Value of Tests; D012720:Severity of Illness Index; D020521:Stroke / Q000473:pathology* / Q000628:therapy*
D015415:Biomarkers