title: ALS clinical trials: do enrolled patients accurately represent the ALS population?
abstract: OBJECTIVE
  To assess the effect of eligibility criteria in amyotrophic lateral sclerosis (ALS) clinical trials on the representativeness of the enrolled population.
  
  
  METHODS
  Patients enrolled in 8 placebo-controlled clinical trials in our ALS center from 2003 to 2008 were compared 1) to the patients included a prospective epidemiologic register (Piemonte and Valle d'Aosta register for ALS, PARALS) in the same period and 2) the subset of PARALS patients who met the usual criteria for inclusion in clinical trials (PARALS-ct) (definite, probable, probable laboratory-supported ALS; age between 18 and 75 years; disease duration <36 months; vital capacity at diagnosis ≥70%; score ≥3 at the items swallowing and respiratory insufficiency at the Amyotrophic Lateral Sclerosis Functional Rating Scale-revised scale; riluzole therapy).
  
  
  RESULTS
  A total of 164 patients were enrolled in 8 different clinical trials. The PARALS cohort included 813 patients, of whom 539 (66.3%) met the entry criteria for clinical trials. Patients enrolled in clinical trials were different from both epidemiologic cohorts, since they were younger, had a longer diagnostic delay, and were more likely to have a spinal onset, and to be men. Tracheostomy-free survival was significantly longer in the group of patients enrolled in clinical trials (median survival time, trial patients, 3.9 years [95% confidence interval (CI) 3.4-4.4]; PARALS, 2.6 [2.4-2.8]; PARALS-ct, 2.9 [2.7-3.1]).
  
  
  CONCLUSIONS
  Patients enrolled in clinical trials do not satisfactorily represent the ALS population; consequently, the findings of ALS trials lack of external validity (generalizability). Efforts should be made to improve patients' recruitment in trials, particularly enrolling incident rather than prevalent cases.
authors.affiliation: ALS Centre, Department of Neuroscience, University of Turin, Turin. achio@usa.net
authors.forename: A
authors.initials: A
authors.lastname: Chiò
authors.forename: A
authors.initials: A
authors.lastname: Canosa
authors.forename: S
authors.initials: S
authors.lastname: Gallo
authors.forename: S
authors.initials: S
authors.lastname: Cammarosano
authors.forename: C
authors.initials: C
authors.lastname: Moglia
authors.forename: G
authors.initials: G
authors.lastname: Fuda
authors.forename: A
authors.initials: A
authors.lastname: Calvo
authors.forename: G
authors.initials: G
authors.lastname: Mora
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000188:drug therapy* / Q000401:mortality; D015331:Cohort Studies; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007558:Italy; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D018579:Patient Selection; D016032:Randomized Controlled Trials as Topic / Q000379:methods / Q000592:standards*; D012189:Retrospective Studies; D055815:Young Adult