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Enrollment bias: frequency and impact on patient selection in endovascular stroke trials
  1. Sunil A Sheth1,3,
  2. Jeffrey L Saver1,
  3. Sidney Starkman1,2,
  4. Ileana D Grunberg1,2,
  5. Judy Guzy1,2,
  6. Latisha K Ali1,
  7. Doojin Kim1,
  8. Nestor R Gonzalez3,4,
  9. Reza Jahan3,
  10. Satoshi Tateshima3,
  11. Gary Duckwiler3,
  12. David S Liebeskind1
  1. 1Department of Neurology, Comprehensive Stroke Center, University of California Los Angeles, Los Angeles, California, USA
  2. 2Department of Emergency Medicine, University of California Los Angeles, Los Angeles, California, USA
  3. 3Division of Interventional Neuroradiology, University of California Los Angeles, Los Angeles, California, USA
  4. 4Department of Neurosurgery, University of California Los Angeles, Los Angeles, California, USA
  1. Correspondence to Dr S A Sheth, Division of Interventional Neuroradiology, 757 Westwood Plaza, Suite 2129, Los Angeles, CA 90095-7430, USA; ssheth{at}post.harvard.edu

Abstract

Background Selection bias may have affected enrollment in first generation endovascular stroke trials. We investigate, evaluate, and quantify such bias for these trials at our institution.

Methods Demographic, clinical, imaging, and angiographic data were prospectively collected on a consecutive cohort of patients with acute ischemic stroke who were enrolled in formal trials of endovascular stroke therapy (EST) or received EST in clinical practice outside of a randomized trial for acute cerebral ischemia at a single tertiary referral center from September 2004 to December 2012.

Results Among patients considered appropriate for EST in practice, 47% were eligible for trials, with rates for individual trials ranging from 17% to 70%. Compared with trial ineligible patients treated with EST, trial eligible patients were younger (67 vs 74 years; p<0.05), more often treated with intravenous tissue plasminogen activator (53% vs 34%; p<0.01), and had shorter last known well to puncture times (328 vs 367 min; p<0.05). Focusing on the largest trial with a non-interventional control arm, compared with trial eligible patients treated with EST outside the trial, enrolled patients presented later (274 vs 163 min; p<0.001), had higher National Institutes of Health Stroke Scale scores (20 vs 17; p<0.05), and larger strokes (diffusion weighted imaging volumes 49 vs 18; p<0.001).

Conclusions The majority of patients felt suitable for EST at our institution were excluded from recent trials. Formal entry criteria succeeded in selecting patients with better prognostic features, although many of these patients were treated outside of trials. Acknowledging and mitigating these biases will be crucial to ongoing investigations.

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