This proposal is designed to provide data management and statistical support for the companion application Phase Ill Trial of Minocycline in ALS: I--Clinical Center (P.I. Paul Gordon, University of New Mexico) which is a multicenter clinical tdal of minocycline in ALS. The clinical tdal is a randomized (1:1) double-blind, placebo controlled trial which will enroll 400 patients during the first two years. Each patient will be followed monthly for a minimum of 13 months; the first four months without drug or placebo (monitoring phase) to measure rate of decline of a validated functional measure (ALS Functional Rating Scale-Revised, ALSFRS-R), followed by 9 months on drug or placebo (assigned by randomization). The primary test of drug efficacy will be based on comparing changes in slope, i.e. the slope after assignment (based on up to 9 monthly scores) minus the slope before assignment (based on 5 monthly scores), in the drug versus placebo groups. A linear mixed effects model will be used to estimate the average change of slope for patients in each group. The difference in average change, drug vs. placebo, will be tested using a mixed linear effects model. The study has 80% power to detect a change of 15% in slope which corresponds to 4-5 months of prolonged survival. The companion application Phase III Trial of Minocycline in ALS: I - Clinical Center ( (P.I. Paul Gordon, University of New Mexico) describes the details of background, clinical procedures and human subjects. This application describes the specific aims of the Data Management Center, and summarizes results of our previous clinical trials and studies in ALS. We provide data from our previous studies to justify the 4 month lead-in, thereby reducing sample size. We present an analysis of our previous results to support our choice of the primary and secondary efficacy variables. In particular we demonstrate a close relation between changes in ALSFRS and survival. We explain the selection of the effect size and development of the sample size in detail, based on analysis of our previous results. The details of data management are described, including the methods for quality control, security and information technology. Finally, the analytic plan is described in full.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Project (R01)
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National Institute of Neurological Disorders and Stroke Initial Review Group (NSD)
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Conwit, Robin
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California Pacific Medical Center Research Institute
San Francisco
United States
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