Abstract 36: Acute Stroke Evolution is in the Eye of the Beholder: Effects of Interrater Variability on Patient Selection and Outcomes in the Mr Witness (nct01282242) Multicenter Thrombolysis Trial
Background: MR WITNESS was a safety trial giving tPA to acute ischemic stroke (AIS) patients with unwitnessed onset with MRI findings of early stroke. A DWI-positive, FLAIR negative pattern has been shown to identify strokes <4.5 hr duration, but visual inspection alone may be unreliable and insensitive. Signal intensity ratios (SIR) of manual outlines (lesion/contralateral side) increase sensitivity but can lead to variability in patient selection. We investigated the influence of interrater variability on clinical and safety outcomes.
Methods: Core readers blinded to enrollment status and clinical presentation reviewed MRI of screened patients. The MR WITNESS algorithm enrolled subjects with no visible FLAIR or a pre-specified SIR <1.15. Good outcome was defined as 90 Day modified Rankin Scale (mRS) <2. SIR consistency was measured with intraclass coefficient (ICC) and reader agreement assessed with Fleiss’ Kappa. Statistical analysis included 2-sided Fisher’s Exact test or Wilcoxon Exact test as appropriate.
Results: 201 subjects were screened. 153 baseline MRIs with DWI lesions were reviewed. ICC was 71% (P<.001) and kappa was 67% (P<.0001). Among the 80 subjects enrolled using SIR <1.15 by site reading, 15 (18.8%) subjects would have been excluded based on Core readings. These 15 subjects were younger with worse NIHSS and 90-day mRS (Table). Subset analyses of subjects with pre-stroke mRS<2 showed no statistical difference (P=0.19) between subjects deemed eligible and not eligible by core readers. No difference in hemorrhagic transformation (HT) or good outcome rates was found. Using SIR <1.25 would have only excluded 3 subjects by Core readings, all of whom had HT, and poor 90 day outcomes.
Discussion: Although SIR reads between Core and sites showed good agreement, there was still variability in the absolute values. This demonstrates the potential limitation of subjective lesion volume delineation. Automated approaches should be investigated.
Author Disclosures: O. Wu: Research Grant; Significant; PI of MR WITNESS NINDS P50NS051343, NINDS R01NS082285, NINDS R01NS086905. Other Research Support; Significant; Genentech provided additional site supplemental payments for MR WITNESS and support for a parallel expanded selection arm of the trial. Consultant/Advisory Board; Modest; Penumbra. L.L. Latour: None. S.S. Song: Employment; Significant; Cedars Sinai Medical Center. Research Grant; Significant; NIH, CCF. Consultant/Advisory Board; Modest; Boehringer Ingelheim & Portola. W.A. Copen: None. A.J. Yoo: None. M.H. Lev: None. A.L. Ford: None. A. Hsia: None. R. Betensky: None. A. Muzikansky: None. G. Boulouis: None. A. Lauer: None. P. Cougo: None. G.J. Harris: None. S. Warach: None. L.H. Schwamm: Research Grant; Significant; Principal investigator of an investigator-initiated study of extended-window intravenous thrombolysis funded by the National Institutes of Neurological Disorders and Stroke (clinicaltrials.gov/show/NC. Other Research Support; Significant; Genentech provides alteplase free of charge to Massachusetts General Hospital as well as supplemental per-patient payments to participating sites in an investigator-initiated trial of extended-window. Consultant/Advisory Board; Modest; Stroke Systems consultant to the Massachusetts Department of Public Health. Consultant/Advisory Board; Significant; Lundbeck (international steering committee, DIAS3, 4 trial), Penumbra (data and safety monitoring committee, Separator 3D trial), Medtronic (Victory AF, REACT AF and Stroke AF trials). Other; Modest; Chair of the AHA/ASA GWTG Stroke Clinical work group (unpaid).
- © 2017 by American Heart Association, Inc.