Sample size estimates for determining treatment effects in high-risk patients with early relapsing-remitting multiple sclerosis

Background: Risk factors for short-term progression in early relapsing-remitting MS have been identified recently. Previously we determined potential risk factors for rapid progression of early relapsing-remitting MS and identified three groups of high-risk patients. These non-mutually exclusive groups of patients were drawn from a consecutively studied sample of 98 patients with newly diagnosed MS. High-risk patients had a history of either poor recovery from initial attacks, more than two attacks in the first two years of disease, or a combination of at least four other risk factors. Objective: To determine differences in sample sizes required to show a meaningful treatment effect when using a high-risk sample versus a random sample of patients. Methods: Power analyses were used to calculate the different sample sizes needed for hypothetical treatment trials. Results: We found that substantially smaller numbers of patients should be needed to show a significant treatment effect by employing these high-risk groups of patients as compared to a random population of MS patients (e.g., 58% reduction in sample size in one model). Conclusion: The use of patients at higher risk of progression to perform drug treatment trials can be considered as a means to reduce the number of patients needed to show a significant treatment effect for patients with very early MS.