Minimal Clinically Important Difference for Safe and Simple Novel Acute Ischemic Stroke Therapies.

Abstract

Determining the minimal clinically important difference (MCID) is essential for evaluating novel therapies. For acute ischemic stroke, expert surveys have yielded MCIDs that are substantially higher than the MCIDs observed in actual expert behavior in guideline writing and clinical practice, potentially because of anchoring bias. We administered a structured, internet-based survey to a cross-section of academic stroke neurologists in the United States. Survey responses assessed demographic and clinical experience, and expert judgment of the MCID of the absolute increase needed in the proportion of patients achieving functional independence at 3 months to consider a novel, safe neuroprotective agent as clinically worthwhile. To mitigate anchoring bias, the survey response framework used a base 1000 rather than base 100 patient framework. Survey responses were received from 122 of 333 academic stroke neurologists, there were 23% women, 72.8% had ≥6 years of practice experience, and neurovascular disease accounted for more than half of practice time in >70%. Responder-nonresponder and continuum of resistance tests indicated that responders were representative of the full expert population. Among respondents, the median MCID was 1.3% (interquartile range, 0.8% to >2%). Stroke expert responses to MCID surveys are affected by anchoring and centrality bias. When survey design takes these into account, the expert-derived MCID for a safe acute ischemic stroke treatment is 1.1% to 1.5%, in accord with actual physician behavior in guideline writing and clinical practice. This revised MCID value can guide clinical trial design and grant-funding and regulatory agency decisions.