The Ethics of Thrombolytic Trials Beyond 3 (or 4.5) Hours

For several decades, clinicians across all fields of internal medicine have embraced the concept of practice guidelines based on levels of evidence. Medical practice in our careers has been transformed from opinion-driven behavior to a reliance on carefully assessed evidence, ranked according to its strength. Ultimately, we expect level 1 evidence for any new therapy, namely adequately powered and conducted randomized, prospective clinical trials. This has facilitated a universal benchmark for clinical practice throughout the world, with only minor regional variations. In acute stroke, this has led to the recommended use of intravenous tissue plasminogen activator within 3 hours, aspirin within 48 hours, management in stroke care units, and, more recently, hemicraniectomy in selected cases of malignant cerebral edema.1How, then, does this principle apply to the …