Development of a Clinically Relevant Outcome Measure for FSHD Therapeutic Trials

描述（由申请人提供）：面肩肱型肌营养不良症（FSHD）是第二常见的成人肌营养不良症。最近发现的 FSHD 的遗传和分子基础表明了治疗干预的独特机会。与此同时，美国食品和药物管理局 (FDA) 已将经过验证的患者报告结果指标确定为可接受的、有时是确定治疗益处的首选机制。虽然针对 FSHD 的新型基因和对症疗法正在迅速开发，但该疾病缺乏有效、有反应、FSHD 特异性、患者相关结果的试验准备。如果不解决 FSHD 临床试验准备问题，有前景的 FSHD 疗法和干预措施的开发和研究将受到阻碍。该提案将开发、测试和验证特定疾病患者报告的结果测量，用于 FSHD 治疗试验。具体目标 1：利用我们对 328 名面肩肱型肌营养不良症 (FSHD) 患者进行的横断面研究的数据来制定 FSHD 健康指数，这是一套能够检测 FSHD 患者健康多个领域有意义的变化的综合问题集。具体目标 2：通过定性访谈优化 FSHD 健康指数。具体目标 3：通过对 FSHD 患者进行为期 12 个月的纵向研究，评估并最大限度地提高 FSHD 健康指数的反应性。具体目标 4：评估 FSHD 健康指数的重测可靠性，并确定其区分不同疾病严重程度的 FSHD 队列的能力。未来方向： 具体目标 5：使用 FSHD 健康指数： 1) 在预期的 FSHD 治疗试验中； 2) 作为开发针对常见肌肉骨骼疾病的其他疾病特异性仪器的模型。这项研究将与菲尔兹 FSHD 研究中心、国家 FSHD 患者登记处、国家关节炎、肌肉骨骼和皮肤疾病研究所 (NIAMS)、行业合作伙伴以及 FSHD 临床和基础科学研究人员密切合作进行。我们预计该提案的结果将使临床医生和研究人员能够纳入有效的患者 FSHD 临床试验中的相关终点。

DESCRIPTION (provided by applicant): Facioscapulohumeral muscular dystrophy (FSHD) is the second most common adult muscular dystrophy. The recently discovered genetic and molecular underpinnings of FSHD suggest unique opportunities for therapeutic intervention. Meanwhile, the U.S. Food and Drug Administration (FDA) have identified validated patient reported outcome measures as an acceptable and at times preferred mechanism for determining therapeutic benefit. While novel genetic and symptomatic therapies are rapidly being developed for FSHD, trial readiness in the form of valid, responsive, FSHD-specific, patient-relevant outcomes for this disease are lacking. If FSHD clinical trial readiness is not addressed, the development and study of promising FSHD therapies and interventions will be hindered. This proposal will develop, test, and validate a disease-specific patient reported outcome measure for use in FSHD therapeutic trials. Specific Aim 1: To use data from our cross-sectional study of 328 facioscapulohumeral muscular dystrophy (FSHD) patients to develop the FSHD-Health Index, a comprehensive question set capable of detecting meaningful change in multiple areas of FSHD patients' health. Specific Aim 2: To optimize the FSHD-Health Index using qualitative interviews. Specific Aim 3: To evaluate and maximize the responsiveness of the FSHD-Health Index through a 12 month longitudinal study of FSHD patients. Specific Aim 4: To evaluate the test-retest reliability of the FSHD-Health Index and determine its ability to differentiate between FSHD cohorts with different disease severity. Future Directions: Specific Aim 5: To use the FSHD-Health Index: 1) In anticipated FSHD therapeutic trials; and, 2) As a model for the development of additional disease-specific instruments for common musculoskeletal disorders. This study will be conducted in close collaboration with The Fields Center for FSHD Research, the National Registry of FSHD patients, the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), industry partners, and with FSHD clinical and basic science researchers. We anticipate that findings from this proposal will enable clinicians and investigators to incorporate a valid patient relevant endpoint in FSHD clinical trials.