The PRO-ACT database Design, initial analyses, and predictive features
The PRO-ACT database Design, initial analyses, and predictive features
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DOI：
10.1212/wnl.0000000000000951
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发表时间：
2014-11-04
期刊：
影响因子：
9.9
通讯作者：
Leitner, Melanie
中科院分区：
文献类型：
--
作者：
Atassi, Nazem;Berry, James;Leitner, Melanie
目的：从已完成的肌萎缩侧索硬化症（ALS）的临床试验数据池，并创建一个开放获取的资源，使更好地了解ALS.Methods的表型和生物学：临床试验数据汇总从16个已完成的II/III期ALS临床试验和一项观察性研究。从超过8，600名ALS患者中纵向收集的超过800万个去识别数据点在试验中进行了标准化，并合并以创建汇集资源开放获取ALS临床试验（PRO-ACT）数据库。该数据库包括人口统计学、家族史以及纵向临床和实验室数据。采用混合效应模型描述疾病进展率，采用修订的ALS功能评定量表（ALSFRS-R）和肺活量（VC）测量。考克斯回归模型用于描述生存数据。结果：ALSFRS-R下降率为1.02（+/-2.3）点/月，VC下降率为预测值的2.24%（+/-6.9）/月。进入试验时较高的尿酸水平预示着ALSFRS-R（p = 0.01）和VC（p < 0.0001）下降较慢，生存期较长（p = 0.02）。基线时肌酐水平较高预示ALSFRS-R（p = 0.01）和VC（p < 0.0001）下降较慢，生存期较长（p = 0.01）。最后，基线时较高的体重指数（BMI）与较长的生存期相关（p < 0.0001）。结论：PRO-ACT数据库是最大的合并ALS临床试验数据的公开可用存储库。我们报告说，肌酐和尿酸的基线水平，以及基线BMI，是疾病进展和生存的强有力的预测因素。
Objective: To pool data from completed amyotrophic lateral sclerosis (ALS) clinical trials and create an open-access resource that enables greater understanding of the phenotype and biology of ALS.Methods: Clinical trials data were pooled from 16 completed phase II/III ALS clinical trials and one observational study. Over 8 million de-identified longitudinally collected data points from over 8,600 individuals with ALS were standardized across trials and merged to create the Pooled Resource Open-Access ALS Clinical Trials (PRO-ACT) database. This database includes demographics, family histories, and longitudinal clinical and laboratory data. Mixed effects models were used to describe the rate of disease progression measured by the Revised ALS Functional Rating Scale (ALSFRS-R) and vital capacity (VC). Cox regression models were used to describe survival data. Implementing Bonferroni correction, the critical p value for 15 different tests was p = 0.003.Results: The ALSFRS-R rate of decline was 1.02 (+/-2.3) points per month and the VC rate of decline was 2.24% of predicted (+/-6.9) per month. Higher levels of uric acid at trial entry were predictive of a slower drop in ALSFRS-R (p = 0.01) and VC (p < 0.0001), and longer survival (p = 0.02). Higher levels of creatinine at baseline were predictive of a slower drop in ALSFRS-R (p = 0.01) and VC (p < 0.0001), and longer survival (p = 0.01). Finally, higher body mass index (BMI) at baseline was associated with longer survival (p < 0.0001).Conclusion: The PRO-ACT database is the largest publicly available repository of merged ALS clinical trials data. We report that baseline levels of creatinine and uric acid, as well as baseline BMI, are strong predictors of disease progression and survival.