With advances in the understanding of the pathophysiology of dystonia, novel therapeutics are being developed. Such therapies will require clinical investigation ranging from exploratory studies to examine safety, tolerability, dosage selection, and preliminary efficacy to confirmatory studies to evaluate efficacy definitively. As dystonia is a rare and complex disorder with clinical and etiological heterogeneity, clinical trials will require careful consideration of the trial design, including enrollment criteria, concomitant medication use, and outcome measures. Given the complexities of designing and implementing efficient clinical trials, it is important for clinicians and statisticians to collaborate closely throughout the clinical development process and that each has a basic understanding of both the clinical and statistical issues that must be addressed. To facilitate designing appropriate clinical trials in this field, we review important general clinical trial and regulatory principles, and discuss the critical components of trials with an emphasis on considerations specific to dystonia. Additionally, we discuss designs used in early exploratory, late exploratory, and confirmatory phases, including adaptive designs.
KeywordsDystonia Clinical trials Exploratory trials Confirmatory trials Adaptive designs
This article was based, in part, on a workshop that was held in May 2012 involving an international group of dystonia clinicians, clinical trialists, and statisticians, as well as representatives from industry and the US Food and Drug Administration. The workshop was sponsored by the Dystonia Medical Research Foundation, The Dystonia Coalition (U54 NS65701 from NINDS and the Office of Rare Diseases Research in NCATS at NIH), and the National Institute of Neurological Disorders and Stroke (U13NS079084). Full conflict of interest disclosures are available in the electronic supplementary material for this article.
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