Fiona B Young1, Christopher J Weir, Kennedy R Lees. 1. Division of Cardiovascular and Medical Sciences, Department of Cerebrovascular Medicine, University of Glasgow, Glasgow, UK. Fby1w@clinmed.gla.ac.uk
Abstract
BACKGROUND AND PURPOSE: Acute stroke trials typically use disability scales as their primary end point. Neurologic impairment scales such as the National Institutes of Health Stroke Scale (NIHSS) are possibly more sensitive to change in patient status. We aimed to compare a range of potential NIHSS end points with modified Rankin Scale (mRS) and Barthel Index (BI) end points. METHODS: We simulated a total of 6000 clinical trials, each with 1400 patients. We estimated statistical power for a range of NIHSS end points, including prognosis-adjusted and fixed dichotomized end points. These end points were compared with the BI and mRS dichotomized at 95 and 1, respectively. RESULTS: The most powerful fixed end point was the NIHSS dichotomized at 1. For prognosis-adjusted outcome, we found greatest power if we defined success as achieving a score of < or =1 or improvement by at least 11 points from baseline. We are more likely to achieve a statistically significant result by using this prognosis-adjusted end point instead of NIHSS < or =1 (odds ratio, 2.8; 95% confidence interval [CI], 2.5 to 3.2). Use of the optimal NIHSS prognosis-adjusted end point rather than BI > or =95 could justify a reduction in sample size of approximately 68% (95% CI, 67% to 69%) without loss of statistical power. CONCLUSIONS: The NIHSS neurologic scale appears more sensitive than the BI or mRS, allowing smaller sample sizes or greater statistical power. The use of an NIHSS prognosis-adjusted end point could allow therapeutic effects from drugs to be more easily identified.
BACKGROUND AND PURPOSE: Acute stroke trials typically use disability scales as their primary end point. Neurologic impairment scales such as the National Institutes of Health Stroke Scale (NIHSS) are possibly more sensitive to change in patient status. We aimed to compare a range of potential NIHSS end points with modified Rankin Scale (mRS) and Barthel Index (BI) end points. METHODS: We simulated a total of 6000 clinical trials, each with 1400 patients. We estimated statistical power for a range of NIHSS end points, including prognosis-adjusted and fixed dichotomized end points. These end points were compared with the BI and mRS dichotomized at 95 and 1, respectively. RESULTS: The most powerful fixed end point was the NIHSS dichotomized at 1. For prognosis-adjusted outcome, we found greatest power if we defined success as achieving a score of < or =1 or improvement by at least 11 points from baseline. We are more likely to achieve a statistically significant result by using this prognosis-adjusted end point instead of NIHSS < or =1 (odds ratio, 2.8; 95% confidence interval [CI], 2.5 to 3.2). Use of the optimal NIHSS prognosis-adjusted end point rather than BI > or =95 could justify a reduction in sample size of approximately 68% (95% CI, 67% to 69%) without loss of statistical power. CONCLUSIONS: The NIHSS neurologic scale appears more sensitive than the BI or mRS, allowing smaller sample sizes or greater statistical power. The use of an NIHSS prognosis-adjusted end point could allow therapeutic effects from drugs to be more easily identified.
Authors: Adnan I Qureshi; Saqib A Chaudhry; Biggya L Sapkota; Gustavo J Rodriguez; M Fareed K Suri Journal: Arch Phys Med Rehabil Date: 2012-03-21 Impact factor: 3.966
Authors: Elisabeth A Wilde; Stephen R McCauley; Tara M Kelly; Annie M Weyand; Claudia Pedroza; Harvey S Levin; Guy L Clifton; Kathleen P Schnelle; Monika V Shah; Paolo Moretti Journal: J Neurotrauma Date: 2010-06 Impact factor: 5.269
Authors: Heidi Sucharew; Jane Khoury; Charles J Moomaw; Kathleen Alwell; Brett M Kissela; Samir Belagaje; Opeolu Adeoye; Pooja Khatri; Daniel Woo; Matthew L Flaherty; Simona Ferioli; Laura Heitsch; Joseph P Broderick; Dawn Kleindorfer Journal: Stroke Date: 2013-05-23 Impact factor: 7.914
Authors: Sabina P W Guenther; Roman Hornung; Dominik Joskowiak; Polyxeni Vlachea; Katharina Feil; Martin Orban; Sven Peterss; Frank Born; Jörg Hausleiter; Steffen Massberg; Christian Hagl Journal: Interact Cardiovasc Thorac Surg Date: 2021-04-19