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Selecting promising ALS therapies in clinical trials

From the Department of Biostatistics (Y.K.C., B.L.), Columbia University Mailman School of Public Health; and The Eleanor and Lou Gehrig MDA/ALS Research Center (P.H.G.), Department of Neurology, Columbia University Medical Center, New York, NY.

Address correspondence and reprint requests to Dr. Ying Kuen Cheung, Department of Biostatistics, Columbia University, 722 West 168th Street, Room 641, New York, NY 10032; e-mail: yc632{at}columbia.edu

Riluzole is the only approved medication that extends survival for patients with amyotrophic lateral sclerosis (ALS). While other potential neuroprotective agents have been evaluated in randomized clinical trials, none has shown unequivocal success and none has been approved by regulatory agencies. Few symptomatic therapies have been tested in ALS. Effectiveness for drugs with modest benefit can be established only through large phase III randomized clinical trials. With numerous potential agents but limited resources, priority should be given to agents that show promise in phase II trials before proceeding to evaluation in phase III trials. In this article, we review drug development in early phase ALS trials and introduce novel designs. First, to maximize the therapeutic potential of the test medication, we need to identify the highest dose that produces a tolerable level of side effects. Second, candidate treatments should be ranked by conducting randomized selection trials between competing new treatments. The selection paradigm adopts a statistical viewpoint different from the hypothesis testing framework in conventional trials. We exemplify this approach by describing a group-sequential selection design developed for a phase II, randomized, multicenter trial of two combination treatments in patients with ALS, and illustrate the sample size reduction from a conventional trial.

Supported by grant ALSA #920.

Disclosure: The authors report no conflicts of interest.

Received March 22, 2006. Accepted in final form July 17, 2006.

This article has been cited by other articles:

				J. D. Glass, M. Benatar, M. Polak, Y. K. Cheung, P. H. Gordon, and B. Levin SELECTING PROMISING ALS THERAPIES IN CLINICAL TRIALS Neurology, May 1, 2007; 68(18): 1545 - 1546. [Full Text] [PDF]

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