RT Journal Article
SR Electronic
T1 The PRO-ACT database
JF Neurology
JO Neurology
FD Lippincott Williams & Wilkins
SP 1719
OP 1725
DO 10.1212/WNL.0000000000000951
VO 83
IS 19
A1 Atassi, Nazem
A1 Berry, James
A1 Shui, Amy
A1 Zach, Neta
A1 Sherman, Alexander
A1 Sinani, Ervin
A1 Walker, Jason
A1 Katsovskiy, Igor
A1 Schoenfeld, David
A1 Cudkowicz, Merit
A1 Leitner, Melanie
YR 2014
UL http://n.neurology.org/content/83/19/1719.abstract
AB 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.ALS=amyotrophic lateral sclerosis; ALSFRS=ALS Functional Rating Scale; ALSFRS-R=revised ALS Functional Rating Scale; BMI=body mass index; CDS=common data structure; CI=confidence interval; HR=hazard ratio; PRO-ACT=Pooled Resource Open-Access ALS Clinical Trials; VC=vital capacity