BACKGROUND AND PURPOSE: The neutral results of the SAINT II trial have again highlighted difficulties translating neuroprotective efficacy from bench to bedside. Animal studies are susceptible to study quality biases, which may lead to overstatement of efficacy. We report the impact of study quality on published estimates of the efficacy of NXY-059 in animal models of stroke. METHODS: We conducted a systematic review and stratified meta-analysis of published studies describing the efficacy of NXY-059 in experimental focal cerebral ischemia. RESULTS: Overall, NXY-059 improved infarct volume by 43.3% (95% CI, 34.7 to 52.8). Only 2 of 9 publications reported randomization, concealment of treatment allocation, and blinded outcome assessment. Studies not reporting these quality items gave substantially higher estimates of efficacy than did higher-quality studies. CONCLUSIONS: The reported efficacy of NXY-059 in animal models of stroke is confounded by low study quality. The failure of SAINT II highlights the need for substantial improvements in the design, conduct, and reporting of animal studies; journals can play an important role in this by adopting standards for animal studies similar to those agreed over 10 years ago for clinical trials.
BACKGROUND AND PURPOSE: The neutral results of the SAINT II trial have again highlighted difficulties translating neuroprotective efficacy from bench to bedside. Animal studies are susceptible to study quality biases, which may lead to overstatement of efficacy. We report the impact of study quality on published estimates of the efficacy of NXY-059 in animal models of stroke. METHODS: We conducted a systematic review and stratified meta-analysis of published studies describing the efficacy of NXY-059 in experimental focal cerebral ischemia. RESULTS: Overall, NXY-059 improved infarct volume by 43.3% (95% CI, 34.7 to 52.8). Only 2 of 9 publications reported randomization, concealment of treatment allocation, and blinded outcome assessment. Studies not reporting these quality items gave substantially higher estimates of efficacy than did higher-quality studies. CONCLUSIONS: The reported efficacy of NXY-059 in animal models of stroke is confounded by low study quality. The failure of SAINT II highlights the need for substantial improvements in the design, conduct, and reporting of animal studies; journals can play an important role in this by adopting standards for animal studies similar to those agreed over 10 years ago for clinical trials.
Authors: Victoria E O'Collins; Malcolm R Macleod; Geoffrey A Donnan; David W Howells Journal: J Cereb Blood Flow Metab Date: 2012-02-01 Impact factor: 6.200
Authors: Victoria E O'Collins; Malcolm R Macleod; Susan F Cox; Leena Van Raay; Elena Aleksoska; Geoffrey A Donnan; David W Howells Journal: J Cereb Blood Flow Metab Date: 2010-10-27 Impact factor: 6.200
Authors: Alicia Aliena-Valero; Júlia Baixauli-Martín; María Castelló-Ruiz; Germán Torregrosa; David Hervás; Juan B Salom Journal: J Cereb Blood Flow Metab Date: 2020-11-19 Impact factor: 6.200
Authors: Story C Landis; Susan G Amara; Khusru Asadullah; Chris P Austin; Robi Blumenstein; Eileen W Bradley; Ronald G Crystal; Robert B Darnell; Robert J Ferrante; Howard Fillit; Robert Finkelstein; Marc Fisher; Howard E Gendelman; Robert M Golub; John L Goudreau; Robert A Gross; Amelie K Gubitz; Sharon E Hesterlee; David W Howells; John Huguenard; Katrina Kelner; Walter Koroshetz; Dimitri Krainc; Stanley E Lazic; Michael S Levine; Malcolm R Macleod; John M McCall; Richard T Moxley; Kalyani Narasimhan; Linda J Noble; Steve Perrin; John D Porter; Oswald Steward; Ellis Unger; Ursula Utz; Shai D Silberberg Journal: Nature Date: 2012-10-11 Impact factor: 49.962