title: Clinical trial design for endovascular ischemic stroke intervention.
abstract: BACKGROUND
  Randomized, double-blinded, placebo-controlled trials have significant impact on clinical practice. The ultimate goal of a clinical trial of therapy for acute ischemic stroke (AIS) is to compare 2 interventions. Challenges may include interventional therapy standardization, enrollment rate, patient selection, biases, data and safety monitoring, reporting, and financial and logistical support.
  
  
  METHODS
  Selected randomized and single-arm prospective AIS trial designs. Clinical trial elements and their challenges are reviewed. Innovative designs and proposed recommendations to overcome some of the specific challenges and limitations are discussed.
  
  
  RESULTS
  AIS therapy trials have specific challenges related to ethical issues, enrollment rate, outcome measures, limited time to treatment, efficacy, safety, and limited or variable operator experience with complex technology in a delicate end organ. Proposed suggestions for improving trial design include the following: incorporation of a lead-in phase; careful patient and outcome measure selection; historical, concurrent, or hybrid controls; open data access; and a Bayesian approach. An open data paradigm may facilitate creation of computerized prediction models for future trials (minimizing cost by decreasing sample size or providing futility analyses and directing resources to other trials). Collaborative, consortium, and network infrastructures may allow more effective and efficient study completion. Self-learning, self-correcting trials with intrinsic flexibility to adapt may help future clinical trial design in AIS.
  
  
  CONCLUSIONS
  The randomized clinical trial design in AIS endovascular therapy is challenging. Lead-in phases, careful patient selection, use of innovative outcome measures, control groups, and newer clinical trial design may enhance conduct of future trials, their validity, and their results.
authors.affiliation: Department of Neurology, Medical College of Wisconsin and Froedtert Hospital, Milwaukee, WI, USA. szaidat@mcw.edu
authors.forename: Osama O
authors.initials: OO
authors.lastname: Zaidat
authors.forename: David S
authors.initials: DS
authors.lastname: Liebeskind
authors.forename: Randall C
authors.initials: RC
authors.lastname: Edgell
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Amlie-Lefond
authors.forename: Junaid S
authors.initials: JS
authors.lastname: Kalia
authors.forename: Andrei V
authors.initials: AV
authors.lastname: Alexandrov
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000175:diagnosis / Q000628:therapy*; D002985:Clinical Protocols; D002986:Clinical Trials as Topic / Q000379:methods*; D061345:Early Medical Intervention / Q000379:methods*; D057510:Endovascular Procedures / Q000379:methods*; D006801:Humans; D020521:Stroke / Q000175:diagnosis / Q000628:therapy*