Abstract T P73: Overcoming Framing Bias in Stroke Neurologists’ Assessments of the Minimally Clinically Important Difference for Novel Acute Ischemic Stroke Therapies

Abstract

Background: The determination of the minimally clinically important difference (MCID) worth detecting is an essential prerequisite for clinical trial sample size calculation, funding decisions by NIH and other sponsors, and drug or device approval by regulatory agency. However, prior surveys to establish expert judgment of MCID have had a cognitive framing bias by offering response options with midpoints in the 5-15% range, well above the treatment effect actually accepted in practice and national guidelines as worthwhile (1% for acute aspirin). Methods: A 5 item internet-based survey was administered to US academic stroke neurologists. Respondents were asked to indicate, for an acute neuroprotective drug free of side effects, how many patients, per 1000 treated, would need to benefit by achieving freedom from disability at 90 days (mRS 0-2) for the agent to be worthwhile to use in clinical practice? Results: Survey responses were received from 122 of 332 academic stroke neurologists. Among the participants, 38.0% were professors, 24.0% associate professors, 33.1% assistant professors, and 5.0% neurology residents or fellows. All respondents were engaged in stroke clinical care, with cerebrovascular disease accounting for more than half of practice time in over 75%. Categorized responses to the value of the MCID were: 1 per 1000 by 3.3% of respondents, 2-5 in 7.4%, 6-10 by 19.7%, 11-15 by 22.1%, 16-20 by 15.6%, and greater than 20 by 32.0%. The median MCID was 13 (IQR 8 to > 20). Converted to natural base 100 values, the MCID was 1.3% (IQR 0.8% - >2%). Conclusion: When assessed with framing based on clinical practice rather than convenience, vascular neurologists indicated the minimally clinical important difference for a safe agent to be worthwhile to use in acute ischemic stroke is about 1%. Drug and device agencies should consider this value to be the expert opinion MCID for acute ischemic stroke treatments when making regulatory decisions.