title: The PRO-ACT database: design, initial analyses, and predictive features.
abstract: 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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: From the Neurological Clinical Research Institute (NCRI), Department of Neurology (N.A., J.B., A. Sherman, E.S., J.W., I.K., M.C.), and the Biostatistics Center (A. Shui, D.S.), Massachusetts General Hospital, Boston; and Prize4Life (N.Z., M.L.), Cambridge, MA. natassi@partners.org.
authors.forename: Nazem
authors.initials: N
authors.lastname: Atassi
authors.affiliation: From the Neurological Clinical Research Institute (NCRI), Department of Neurology (N.A., J.B., A. Sherman, E.S., J.W., I.K., M.C.), and the Biostatistics Center (A. Shui, D.S.), Massachusetts General Hospital, Boston; and Prize4Life (N.Z., M.L.), Cambridge, MA.
authors.forename: James
authors.initials: J
authors.lastname: Berry
authors.affiliation: From the Neurological Clinical Research Institute (NCRI), Department of Neurology (N.A., J.B., A. Sherman, E.S., J.W., I.K., M.C.), and the Biostatistics Center (A. Shui, D.S.), Massachusetts General Hospital, Boston; and Prize4Life (N.Z., M.L.), Cambridge, MA.
authors.forename: Amy
authors.initials: A
authors.lastname: Shui
authors.affiliation: From the Neurological Clinical Research Institute (NCRI), Department of Neurology (N.A., J.B., A. Sherman, E.S., J.W., I.K., M.C.), and the Biostatistics Center (A. Shui, D.S.), Massachusetts General Hospital, Boston; and Prize4Life (N.Z., M.L.), Cambridge, MA.
authors.forename: Neta
authors.initials: N
authors.lastname: Zach
authors.affiliation: From the Neurological Clinical Research Institute (NCRI), Department of Neurology (N.A., J.B., A. Sherman, E.S., J.W., I.K., M.C.), and the Biostatistics Center (A. Shui, D.S.), Massachusetts General Hospital, Boston; and Prize4Life (N.Z., M.L.), Cambridge, MA.
authors.forename: Alexander
authors.initials: A
authors.lastname: Sherman
authors.affiliation: From the Neurological Clinical Research Institute (NCRI), Department of Neurology (N.A., J.B., A. Sherman, E.S., J.W., I.K., M.C.), and the Biostatistics Center (A. Shui, D.S.), Massachusetts General Hospital, Boston; and Prize4Life (N.Z., M.L.), Cambridge, MA.
authors.forename: Ervin
authors.initials: E
authors.lastname: Sinani
authors.affiliation: From the Neurological Clinical Research Institute (NCRI), Department of Neurology (N.A., J.B., A. Sherman, E.S., J.W., I.K., M.C.), and the Biostatistics Center (A. Shui, D.S.), Massachusetts General Hospital, Boston; and Prize4Life (N.Z., M.L.), Cambridge, MA.
authors.forename: Jason
authors.initials: J
authors.lastname: Walker
authors.affiliation: From the Neurological Clinical Research Institute (NCRI), Department of Neurology (N.A., J.B., A. Sherman, E.S., J.W., I.K., M.C.), and the Biostatistics Center (A. Shui, D.S.), Massachusetts General Hospital, Boston; and Prize4Life (N.Z., M.L.), Cambridge, MA.
authors.forename: Igor
authors.initials: I
authors.lastname: Katsovskiy
authors.affiliation: From the Neurological Clinical Research Institute (NCRI), Department of Neurology (N.A., J.B., A. Sherman, E.S., J.W., I.K., M.C.), and the Biostatistics Center (A. Shui, D.S.), Massachusetts General Hospital, Boston; and Prize4Life (N.Z., M.L.), Cambridge, MA.
authors.forename: David
authors.initials: D
authors.lastname: Schoenfeld
authors.affiliation: From the Neurological Clinical Research Institute (NCRI), Department of Neurology (N.A., J.B., A. Sherman, E.S., J.W., I.K., M.C.), and the Biostatistics Center (A. Shui, D.S.), Massachusetts General Hospital, Boston; and Prize4Life (N.Z., M.L.), Cambridge, MA.
authors.forename: Merit
authors.initials: M
authors.lastname: Cudkowicz
authors.affiliation: From the Neurological Clinical Research Institute (NCRI), Department of Neurology (N.A., J.B., A. Sherman, E.S., J.W., I.K., M.C.), and the Biostatistics Center (A. Shui, D.S.), Massachusetts General Hospital, Boston; and Prize4Life (N.Z., M.L.), Cambridge, MA.
authors.forename: Melanie
authors.initials: M
authors.lastname: Leitner
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000175:diagnosis / Q000503:physiopathology / Q000628:therapy; D002986:Clinical Trials as Topic / Q000706:statistics & numerical data*; D003628:Database Management Systems; D066264:Datasets as Topic / Q000706:statistics & numerical data*; D018450:Disease Progression; D006801:Humans; D008137:Longitudinal Studies; D064887:Observational Studies as Topic / Q000706:statistics & numerical data; D011237:Predictive Value of Tests; D012107:Research Design