Can we eliminate placebo in ALS clinical trials?

Published

Journal Article

BACKGROUND: Previous studies concluded that the decline in strength in patients with amyotrophic lateral sclerosis (ALS) is a linear function. If so, a patient's natural history might serve as the control, instead of placebo, in a clinical trial. METHODS: A placebo-controlled ALS clinical trial included a natural history phase, followed by a 6-month treatment phase. Each patient's forced vital capacity (FVC) score and maximal voluntary isometric contraction (MVIC) raw scores were measured monthly, standardized, and averaged into megascores. For 138 patients, the arm, leg, FVC, arm+leg combination, and arm+leg+FVC combination megascore slopes during the natural history phase and during the placebo phase were compared. RESULTS: The mean slope of megascores during the natural history phase and the mean slope during the placebo phase were not different for the arm, leg, and arm+leg megascores, but were different for the FVC and arm+leg+FVC combination megascores. CONCLUSIONS: Natural history controls may be useful in ALS exploratory trials that use arm megascore slope as the primary outcome measure. However, there are distinct limitations to the use of natural history controls, so that Phase 3 ALS clinical trials require placebo controls.

Full Text

Duke Authors

Cited Authors

  • Bryan, WW; Hoagland, RJ; Murphy, J; Armon, C; Barohn, RJ; Goodpasture, JC; Miller, RG; Parry, GJ; Petajan, JH; Ross, MA; Stromatt, SC; rhCNTF ALS Study Group,

Published Date

  • April 2003

Published In

Volume / Issue

  • 4 / 1

Start / End Page

  • 11 - 15

PubMed ID

  • 12745612

Pubmed Central ID

  • 12745612

International Standard Serial Number (ISSN)

  • 1466-0822

Language

  • eng

Conference Location

  • England