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From the Department of Biostatistics, Mailman School of Public Health (G.L., R.B., R.A., X.Z., B.L., J.L.P.T.), and Eleanor and Lou Gehrig MDA/ALS Research Center (P.K., J.M., A.B., V.B., H.M.), Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY.
Address correspondence and reprint requests to Dr. Gilberto Levy, Department of Biostatistics, Columbia University, 722 West 168th St., 6th floor, New York, NY 10032; e-mail: GL227{at}columbia.edu
Background: The combination of a small pool of patients at any given time with the availability of many potential neuroprotective agents to be tested in ALS requires efficient phase II trial designs.
Objective: To describe the design of the Clinical Trial of High Dose Coenzyme Q10 (CoQ10) in ALS (QALS study)—a phase II, randomized, placebo-controlled, double-blind, multicenter clinical trial.
Methods: The study design features two stages. The first stage (dose selection) identifies which of two doses of CoQ10 (1800 mg or 2700 mg) is preferred using a selection procedure rather than a formal hypothesis test. The second stage (early efficacy test) compares the preferred dose of CoQ10 against placebo using a non-superiority or futility design. Data from patients assigned to the preferred dose of CoQ10 in the first stage are also used in the second stage. The primary outcome measure is the decline in Amyotrophic Lateral Sclerosis Functional Rating Scale–revised (ALSFRSr) score from baseline to 9 months.
Results: The total sample size required is 185 patients, as compared to a much larger sample size estimated to be necessary using a conventional superiority design (total: 852 patients). The authors report a bias correction made necessary by the inclusion of patient data from the first stage in the second stage.
Conclusions: Several features of the Clinical Trial of High Dose Coenzyme Q10 in ALS study design promote efficiency. These features may be beneficial in phase II trials in amyotrophic lateral sclerosis and other fields.
Additional material related to this article can be found on the Neurology Web site. Go to www.neurology.org and scroll down the Table of Contents for the March 14 issue to find the title link for this article.
Editorial, see page 626
Supported by federal grants National Institute of Neurologic Disorders and Stroke R01 NS48555 (G.L., R.B., R.A., B.L., J.L.P.T.), National Institute of Neurologic Disorders and Stroke R01 NS48125 (P.K., J.M., A.B., V.B., H.M.), and K12RR017648 (P.K.), and an Irving Research Scholar Award (P.K.).
Disclosure: The authors report no conflicts of interest.
Received June 20, 2005. Accepted in final form November 14, 2005.
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