Can we eliminate placebo in ALS clinical trials?

Wilson W. Bryan, Rebecca J. Hoagland, J. Murphy, Carmel Armon, Richard J. Barohn, Jessie C. Goodpasture, Robert G. Miller, Gareth J. Parry, Jack H. Petajan, Mark A. Ross, Scott C. Stromatt, Jerry M. Belsh, Aron S. Buchman, Peter D. Donofrio, Andrew A. Eisen, Richard A. Gan, Laurie Gutmann, Steven H. Horowitz, Carlayne E. Jackon, Wendy S. JohnstonJohn J. Kelly, Raul N. Mandler, Janice M. Massey, Dawn McGuire, Daniel S. Newman, Robert M. Pascuzzi, Jack H. Petajan, Lawrence H. Phillips, Michael H. Rivner, Mark A. Rubin, Louis S. Russo, Stephen M. Sergay, Austin J. Sumner, Michael R. Swenson, Lawrence Teitel

Research output: Contribution to journalArticlepeer-review

15 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)11-15
Number of pages5
JournalAmyotrophic Lateral Sclerosis and Other Motor Neuron Disorders
Issue number1
StatePublished - Apr 2003


  • Amyotrophic lateral sclerosis
  • Motor neuron disease
  • Natural history
  • Neuromuscular diseases
  • Placebo

ASJC Scopus subject areas

  • Clinical Neurology


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