Galpern Wendy R, Coffey Christopher S, Albanese Alberto, Cheung Ken, Comella Cynthia L, Ecklund Dixie J, Fahn Stanley, Jankovic Joseph, Kieburtz Karl, Lang Anthony E, McDermott Michael P, Shefner Jeremy M, Teller Jan K, Thompson John L P, Yeatts Sharon D, Jinnah H A
National Institute of Neurological Disorders and Stroke, National Institutes of Health, 6001 Executive Blvd., Rm 2225, Bethesda, MD, 20892, USA,
Neurotherapeutics. 2014 Jan;11(1):117-27. doi: 10.1007/s13311-013-0221-6.
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.
随着对肌张力障碍病理生理学认识的进展，新型治疗方法正在研发中。此类疗法将需要进行从探索性研究到确认性研究的临床研究，探索性研究用于检查安全性、耐受性、剂量选择和初步疗效，确认性研究用于明确评估疗效。由于肌张力障碍是一种罕见且复杂的疾病，具有临床和病因学异质性，临床试验将需要仔细考虑试验设计，包括纳入标准、合并用药情况和结局指标。鉴于设计和实施高效临床试验的复杂性，临床医生和统计学家在整个临床开发过程中密切合作非常重要，并且双方都应对必须解决的临床和统计问题有基本的了解。为便于在该领域设计合适的临床试验，我们综述重要的一般临床试验和监管原则，并讨论试验的关键组成部分，重点是肌张力障碍特有的考虑因素。此外，我们还讨论早期探索性、晚期探索性和确认性阶段所使用的设计，包括适应性设计。
