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）已将经验证的患者报告的结局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FSHD的新型遗传和对症治疗正在迅速开发，但缺乏有效，反应性，FSHD特异性，患者相关结局形式的试验准备。如果不解决FSHD临床试验准备问题，有前景的FSHD治疗和干预措施的开发和研究将受到阻碍。该提案将开发、测试和验证用于FSHD治疗试验的疾病特异性患者报告结局指标。具体目标1：使用我们对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，开发FSHD健康指数，这是一个能够检测FSHD患者健康多个领域有意义变化的综合问题集。具体目标2：使用定性访谈优化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-健康指数的重测信度，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：具体目标五：使用FSHD-健康指数：1）在预期的FSHD治疗试验中;和，2）作为一个模型，用于开发常见肌肉骨骼疾病的其他疾病特异性工具。本研究将与FSHD研究领域中心，FSHD患者国家登记处，国家关节炎和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。我们预计，这项提案的结果将使临床医生和研究人员能够将一个有效的病人 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.