title: Non-self-sufficiency as a primary outcome measure in ALS trials.
abstract: Our objective was to assess non-self-sufficiency (NSS) in ALS as an outcome measure in therapeutic trials. Using data from the control arm of two randomized trials and an observational study, associations between NSS (score ≤2 in the ALSFRS-R items for swallowing, cutting food and handling utensils, or walking) and the total ALSFRS-R score, forced vital capacity (FVC), and survival at selected time-points until death or 48 weeks, were assessed. These measures were used as surrogates of relevant functional impairment. Of 82 self-sufficient (SS) patients at baseline, 32 (39.0%) became NSS at four weeks and increased to 72 (87.8%) at the end of follow-up. A significant association was found between NSS, ALSFRS-R score and FVC at 24, 36 and 48 weeks. Thirty-four subjects died (41.5%). Compared to SS patients (median survival, 27.9 months), individuals becoming NSS at four weeks were at increased risk to die (median survival, 23.6 months, p = 0.02). NSS status at four weeks predicted survival even after adjustment for ALSFRS-R total score, age, gender, site of onset, disease duration, BMI, and FVC. 'Walking' was the only predictor of survival when adjusting for all covariates. In conclusion, NSS status is a possible endpoint to investigate short-term efficacy of treatments of ALS.
authors.affiliation: a INSERM UMR1094, Tropical Neuroepidemiology , Limoges.|b University of Limoges, School of Medicine, Institute of Neuroepidemiology and Tropical Neurology , CNRS FR 3503 GEIST , Limoges.|c CHU Limoges, Centre d'Epidémiologie de Biostatistique et de Méthodologie de la Recherche , France.|d Laboratory of Neurological Disorders, Department of Neuroscience , IRCCS Institute for Pharmacological Research Mario Negri , Milan.
authors.forename: Benoît
authors.initials: B
authors.lastname: Marin
authors.affiliation: d Laboratory of Neurological Disorders, Department of Neuroscience , IRCCS Institute for Pharmacological Research Mario Negri , Milan.
authors.forename: Elisa
authors.initials: E
authors.lastname: Bianchi
authors.affiliation: d Laboratory of Neurological Disorders, Department of Neuroscience , IRCCS Institute for Pharmacological Research Mario Negri , Milan.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Pupillo
authors.affiliation: e Centro Clinico NEMO , Fondazione Serena Onlus , Milan.
authors.forename: Christian
authors.initials: C
authors.lastname: Lunetta
authors.affiliation: f Neurology Clinic, San Gerardo Hospital and University of Milano-Bicocca , Monza.
authors.forename: Lucio
authors.initials: L
authors.lastname: Tremolizzo
authors.affiliation: g Neurodegenerative Diseases Unit, Department of Basic Medicine Neuroscience and Sense Organs, Department of Clinical Research in Neurology of the University of Bari at 'Pia Fondazione Card. G. Panico' Hospital Tricase (LE) , University of Bari.
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Logroscino
authors.affiliation: h ALS Centre, 'Rita Levi Montalcini' Department of Neuroscience , University of Torino , AOU Città della Salute e della Scienza , Turin , Italy.
authors.forename: Adriano
authors.initials: A
authors.lastname: Chiò
authors.affiliation: a INSERM UMR1094, Tropical Neuroepidemiology , Limoges.|b University of Limoges, School of Medicine, Institute of Neuroepidemiology and Tropical Neurology , CNRS FR 3503 GEIST , Limoges.|c CHU Limoges, Centre d'Epidémiologie de Biostatistique et de Méthodologie de la Recherche , France.
authors.forename: Pierre Marie
authors.initials: PM
authors.lastname: Preux
authors.affiliation: d Laboratory of Neurological Disorders, Department of Neuroscience , IRCCS Institute for Pharmacological Research Mario Negri , Milan.
authors.forename: Ettore
authors.initials: E
authors.lastname: Beghi
mesh_terms: D000203:Activities of Daily Living; D000328:Adult; D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000175:diagnosis* / Q000453:epidemiology / Q000628:therapy*; D002986:Clinical Trials as Topic / Q000379:methods*; D003943:Diagnostic Techniques, Neurological; D004185:Disability Evaluation; D023381:Endpoint Determination / Q000379:methods; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D017063:Outcome Assessment, Health Care / Q000379:methods*; D015995:Prevalence; D011788:Quality of Life; D015203:Reproducibility of Results; D012307:Risk Factors; D020377:Self Efficacy; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D018434:Sickness Impact Profile; D016019:Survival Analysis; D016896:Treatment Outcome
keywords: Amyotrophic lateral sclerosis; clinical trials; non-self-sufficiency; outcome measures