Health-Related Quality of Life in Huntington?s Disease Research and Practice: De

描述（由申请人提供）：NIH路线图认识到“迫切需要更好地量化临床重要症状和结果，包括疼痛、疲劳和生活质量。”美国国立卫生研究院路线图已经导致了前所未有的与健康有关的生活质量（HRQOL）测量开发计划的大规模倡议，用于：1)普通人群（由美国国立卫生研究院资助）；2)成人癫痫、中风、肌萎缩侧索硬化症、多发性硬化症和帕金森病（由NINDS资助）；3)脊髓损伤（由NCMRR和NINDS资助）；4)创伤性脑损伤（由NIDRR和VA RR&D资助）。尽管有这些举措，但用于最具破坏性和使人衰弱的疾病之一——亨廷顿舞蹈病（HD）的HRQOL措施却很少。HD是一种致命的、潜伏的、进行性神经退行性疾病，其特征是运动、认知和精神功能异常，逐渐出现并恶化，直到最终导致死亡。最近，HD基因鉴定的发展推动了旨在恢复功能和治疗继发性并发症的临床试验，为找到治愈这种致命疾病的方法带来了新的希望。目前，缺乏能够评估临床治疗有效性的针对hd的、严格的HRQOL结果指标；需要一种有效的hd特异性HRQOL测量方法来准确测量临床和研究结果。具体而言，本研究将复制上述项目中最先进的定性方法，通过基于社区的合作伙伴关系来确定HD中相关的HRQOL领域/主题，并开发反映这些领域/主题的项目。由患有或有患HD风险的个人（“消费者”）、家庭成员和照顾者以及HD专业人员组成的焦点小组将参与其中，以确定与HD患者生活质量相关的重要问题/主题。两名独立调查人员将审查焦点小组的记录，以确定主要内容领域，并制定HD中HRQOL域的初步清单；这些域将为项目开发提供一个初始结构。在本研究完成后，将寻求未来的资金来测试和验证这些项目，并将包括一个连贯的，全面的，最先进的方法，采用经典和现代的测试构建和验证方法，包括项目反应理论和计算机自适应测试技术。该试点项目与未来的工作相结合，将通过开发一种有意义、有效和简明的HRQOL测量方法，用于HD临床试验的结果测量，来填补这一重大空白。公共卫生相关性：尽管亨廷顿氏病（HD）基因鉴定的发展推动了对这种致命疾病的有效治疗，但目前的评估措施缺乏确定此类治疗对健康相关生活质量（HRQOL）有效性所需的敏感性。本研究的目的是开发一种敏感而有意义的HD患者HRQOL指标。像这样的测量将与身体功能、情绪功能、参与和不良事件（如联合亨廷顿病评定量表）的测量一起作为HD临床试验的核心结果测量。

DESCRIPTION (provided by applicant): The NIH Roadmap recognizes a "pressing need to better quantify clinically important symptoms and outcomes, including pain, fatigue, and quality of life." The NIH Roadmap has lead to an unprecedented number of large-scale initiatives for health-related quality of life (HRQOL) measurement development initiatives for use in: 1) the general population (funded by NIH); 2) adult epilepsy, stroke, amyotrophic lateral sclerosis, multiple sclerosis, and Parkinson's disease (funded by NINDS); 3) spinal cord injury (funded by NCMRR and NINDS); and 4) traumatic brain injury (funded by NIDRR and the VA RR&D). Despite these initiatives, there is a paucity of HRQOL measures for use with one of the most devastating and debilitating diseases, Huntington's disease (HD). HD--a fatal, insidious, progressive neurodegenerative disease--is characterized by abnormalities in motor, cognitive, and psychiatric functions that gradually appear and worsen until eventually causing death. Recently, the development of gene identification in HD has led to a push for clinical trials designed to restore functioning and treat secondary complications, leading to renewed hopes about finding a cure for this deadly disease. Currently, HD-specific, rigorous outcomes measures in HRQOL that are capable of evaluating the effectiveness of clinical treatments are lacking; a valid HD-specific measure of HRQOL is needed to accurately measure both clinical and research outcomes. Specifically, this study will replicate the state-of-the art qualitative methodology of the aforementioned projects for use in HD by using a community based partnership to identify relevant HRQOL domains/themes in HD and develop items that reflect these domains/themes. Focus groups consisting of individuals with or at-risk for HD ("consumers"), family members and caregivers, and HD professionals will be included to identify the important issues/themes related to quality of life in HD. Transcripts from the focus groups will be reviewed by two independent investigators in order to identify major content areas and develop an initial list of HRQOL domains in HD; these domains will provide an initial structure for item development. Upon completion of this study, future funding will be sought to test and validate these items and will include a coherent, comprehensive, state-of-the-art approach, employing both classical and contemporary methods of test construction and validation including Item Response Theory and computerized adaptive testing technology. This pilot project, in conjunction with this future work, will fill a significant void by developing a meaningful, valid and concise measure of HRQOL for use in outcome measurement of HD clinical trials. PUBLIC HEALTH RELEVANCE: Although the development of gene identification in Huntington's disease (HD) has led to a push to find effective treatments for this fatal condition, current assessment measures lack the sensitivity needed to determine the effectiveness of such treatments on health-related quality of life (HRQOL). The purpose of this study is to develop a sensitive and meaningful outcome measure of HRQOL in persons with HD. A measure like this will be used alongside measures of physical functioning, emotional functioning, participation, and adverse events (such as the United Huntington's Disease Rating Scale) as a core outcome measure for clinical trials in HD.