Targeting Neuroprotection Clinical Trials to Ischemic Stroke Patients With Potential to Benefit From Therapy

Author:

Weir Christopher J.1,Kaste Markku1,Lees Kennedy R.1

Affiliation:

1. From the Division of Cardiovascular and Medical Sciences (C.J.W., K.R.L.), University of Glasgow, Gardiner Institute, Western Infirmary, Glasgow, UK; the Department of Neurology (M.K.), Helsinki University Central Hospital, Helsinki, Finland; and the Robertson Centre for Biostatistics (C.J.W), University of Glasgow, Glasgow, UK.

Abstract

Background and Purpose— Clinical trials of neuroprotective drugs have had limited success. We investigated whether selecting patients according to prognostic features would improve the statistical power of a trial to identify an efficacious treatment. Methods— Using placebo data from the Glycine Antagonist in Neuroprotection (GAIN) International and National Institute of Neurological Disorders and Stroke (NINDS) recombinant tissue plasminogen activator (rtPA) clinical trials, we developed and validated simple prognostic models for stroke trial end points: Barthel Index ≥95, modified Rankin Scale ≤1, National Institutes of Health Stroke Scale ≤1, and Glasgow Outcome Scale=1. Using these models, we simulated 1000 clinical trials and estimated, under several hypothetical treatment effect patterns of neuroprotection, the effect on statistical power of including only patients with moderate prognosis. We calculated the number of patients that would have to be enrolled to maintain the statistical power achieved in selecting the whole trial population. Reanalysis of actual data from the NINDS rtPA trials confirmed the results independently. Results— Selecting patients with moderate prognosis (predicted probability of favorable outcome 0.2 to 0.8) enabled a sample size reduction, without loss of statistical power, of between 54.6% (51.3% to 57.6%) and 68.6% (66.0% to 71.1%), depending on the treatment effect pattern and outcome measure. These benefits were largely due to the exclusion of patients with poor prognosis. Conclusions— Targeting patients with potential to benefit enables a substantial sample size reduction without compromising statistical power or duration of recruitment. As part of a broader trial design strategy, informed use of prognostic data available acutely would help in identifying effective neuroprotective treatments.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

Advanced and Specialized Nursing,Cardiology and Cardiovascular Medicine,Neurology (clinical)

Cited by 27 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3