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.
RCT Entities:
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.
Authors: Padmaja Yerramilli-Rao; M Flint Beal; Dai Watanabe; Karl Kieburtz; Elisabeth A de Blieck; Mitsuaki Kitano; Kazunori Hosoe; Iwao Funahashi; Merit E Cudkowicz Journal: Int J Toxicol Date: 2012-01-20 Impact factor: 2.032
Authors: Wendy R Galpern; Christopher S Coffey; Alberto Albanese; Ken Cheung; Cynthia L Comella; Dixie J Ecklund; Stanley Fahn; Joseph Jankovic; Karl Kieburtz; Anthony E Lang; Michael P McDermott; Jeremy M Shefner; Jan K Teller; John L P Thompson; Sharon D Yeatts; H A Jinnah Journal: Neurotherapeutics Date: 2014-01 Impact factor: 7.620
Authors: Phillip A Low; David Robertson; Sid Gilman; Horacio Kaufmann; Wolfgang Singer; Italo Biaggioni; Roy Freeman; Susan Perlman; Robert A Hauser; William Cheshire; Stephanie Lessig; Steven Vernino; Jay Mandrekar; William D Dupont; Thomas Chelimsky; Wendy R Galpern Journal: Lancet Neurol Date: 2014-02-05 Impact factor: 44.182
Authors: Christopher S Coffey; Bruce Levin; Christina Clark; Cate Timmerman; Janet Wittes; Peter Gilbert; Sara Harris Journal: Clin Trials Date: 2012-12 Impact factor: 2.486