: This proposal is designed to provide data management and statistical support for the companion application Phase III Trial of Minocycline in ALS: I-Clinical Center (P.I. Paul Gordon, University of New Mexico), which is a multi-center clinical trial of Minocycline in ALS. The clinical trial 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 vs. 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 relationship 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.
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