• Sharon D Yeatts, Renee H Martin, Christopher S Coffey, Patrick D Lyden, Lydia D Foster, Robert F Woolson, Joseph P Broderick, Marco R Di Tullio, Charles A Jungreis, Yuko Y Palesch, and IMS III Investigators.
• From the Data Coordination Unit, Department of Public Health Sciences, Medical University of South Carolina, Charleston, SC (S.D.Y., R.H.M., L.D.F., R.F.W., Y.Y.P.); Department of Biostatistics, University of Iowa, Iowa City, IA (C.S.C.); Department of Neurology, Cedars-Sinai Medical Center, Los Angeles, CA (P.D.L.); Department of Neurology, University of Cincinnati Academic Health Center, Cincinnati, OH (J.P.B.); Department of Medicine, Division of Cardiology, Columbia University Medical Center, New York, NY (M.R.D.T); and Department of Radiology, Temple University School of Medicine, Philadelphia, PA (C.A.J.).
• Stroke. 2014 May 1;45(5):1408-14.

Background And PurposeInterventional Management of Stroke (IMS) III is a randomized, parallel arm trial comparing the approach of intravenous tissue-type plasminogen activator followed by endovascular treatment with intravenous tissue-type plasminogen activator alone in patients with acute ischemic stroke presenting <3 hours of symptom onset. The trial intended to enroll 900 subjects to ensure adequate statistical power to detect an absolute 10% difference in the percentage of subjects with good outcome, defined as modified Rankin Scale score of 0 to 2 at 3 months. In April 2012, after 656 subjects were randomized, further enrollment was terminated by the National Institute of Neurological Disorders and Stroke based on the prespecified criterion for futility using conditional power<20%.MethodsConditional power was defined as the likelihood of finding statistical significance at the end of the study, given the accumulated data to date and with the assumption that a minimum hypothesized difference of 10% truly exists between the 2 groups. The evolution of study data leading to futility determination is described, including the interaction between the unblinded study statisticians and the Data and Safety Monitoring Board in the complex deliberation of analysis results.ResultsThe futility boundary was crossed at the trial's fourth interim analysis. At this point, based on the conditional power criteria, the Data and Safety Monitoring Board recommended termination of the trial.ConclusionsEven in spite of prespecified interim analysis boundaries, interim looks at data pose challenges in interpretation and decision making, underscoring the importance of objective stopping criteria.Clinical Trial Registration Urlhttp://www.clinicaltrials.gov. Unique identifier: NCT00359424.

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