title: Toward more efficient clinical trials for amyotrophic lateral sclerosis.
abstract: More than 30 phase II or III clinical trials have been carried out in amyotrophic lateral sclerosis (ALS). Only riluzole, however, has been shown to extend survival and/or time to tracheostomy. Many early ALS trials lacked solid pharmacodynamic and pharmacokinetic data for the treatment being tested, challenging the interpretation of the efficacy and pathway relevance. Understanding of the genetics and pathophysiology of ALS has improved considerably in the past decade, but biomarkers of disease activity remain lacking. A more efficient approach to early phase clinical trials is needed to accelerate the identification of useful agents for ALS. Here we summarize our current thinking about phase II design options and the potential benefits of a clinical trial network for phase II trials in ALS.
authors: Massachusetts General Hospital, Boston, Massachusetts, USA. mcudkowicz@partners.org
authors: Merit E
authors: ME
authors: Cudkowicz
authors: Jon
authors: J
authors: Katz
authors: Dan H
authors: DH
authors: Moore
authors: Gilmore
authors: G
authors: O'Neill
authors: Jonathan D
authors: JD
authors: Glass
authors: Hiroshi
authors: H
authors: Mitsumoto
authors: Stanley
authors: S
authors: Appel
authors: Bernard
authors: B
authors: Ravina
authors: Karl
authors: K
authors: Kieburtz
authors: Ira
authors: I
authors: Shoulson
authors: Petra
authors: P
authors: Kaufmann
authors: Jaffar
authors: J
authors: Khan
authors: Ericka
authors: E
authors: Simpson
authors: Jeremy
authors: J
authors: Shefner
authors: Bruce
authors: B
authors: Levin
authors: Valerie
authors: V
authors: Cwik
authors: David
authors: D
authors: Schoenfeld
authors: Swati
authors: S
authors: Aggarwal
authors: Michael P
authors: MP
authors: McDermott
authors: Robert G
authors: RG
authors: Miller
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000188:drug therapy*; D015415:Biomarkers; D017322:Clinical Trials, Phase II as Topic / Q000379:methods*; D006801:Humans; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D012107:Research Design; D019782:Riluzole / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D018696:Neuroprotective Agents; D019782:Riluzole