Abstract 162: The Challenges of Decision-making Regarding Futility in a Randomized Trial: The IMS III Experience
INTRODUCTION: IMS 3 Trial is a multicenter randomized study to compare the effectiveness of the bridging (IV tPA + intra-arterial) therapy to the IV tPA only treatment in patients with acute ischemic stroke presenting within 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 % of subjects with good outcome, defined as mRS score of 0-2 at 3 months. In April 2012, after 656 subjects were randomized, further enrollment was terminated by the NINDS upon recommendation by the DSMB. The decision was based on the pre-specified criterion for futility using conditional power of <20%. We describe the process in which the IMS 3 Trial was deemed futile by the DSMB.
METHOD: Conditional 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 two groups. Hence, it is akin to ordinary statistical power.
RESULTS: The futility boundary was crossed at the Trial’s 4th interim analysis. The details of the evolution of the study that led to the futility determination are presented, including the interaction between the unblinded study statisticians and the DSMB in the complex deliberation of the data analysis results.
CONCLUSION: Even in spite of pre-specifying the parameters of interim analysis, interim looks at the data pose challenges in the interpretation and decision-making. It therefore underscores the importance of taking utmost care in the design of the study, including specification of objective stopping guidelines.
- © 2012 by American Heart Association, Inc.