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上重要的症状和结果，包括疼痛、疲劳和生活质量。”NIH路线图带来了前所未有的大规模健康相关生活质量(HRQOL)测量发展倡议，用于：1)普通人群(由NIH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)；以及4)创伤性脑损伤(由NIDRR和VA RR&D资助)。尽管有这些举措，但用于治疗最具破坏性和最令人衰弱的疾病之一--亨廷顿病(HD)的HRQOL措施很少。HD是一种致命的、潜伏的、进行性的神经退行性疾病，其特征是运动、认知和精神功能的异常，这些异常逐渐出现并恶化，直到最终导致死亡。最近，HD基因识别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，从而重新燃起了人们对找到这种致命疾病的治愈方法的希望。目前，在HRQOL中缺乏针对HD的、能够评估临床治疗有效性的严格的结果测量；需要有效的HD特定的HRQOL测量来准确地测量临床和研究结果。具体地说，这项研究将复制上述项目的最新定性方法，通过基于社区的伙伴关系来确定HD中相关的HRQOL领域/主题，并开发反映这些领域/主题的项目。小组成员包括患有或易患上先天性心脏病的人士(“消费者”)、家庭成员和照顾者，以及患有先天性心脏病的专业人士，以找出与先天性心脏病生活质素有关的重要事项/主题。重点小组的成绩单将由两名独立调查员审查，以确定主要内容领域，并制定HD的HRQOL领域的初步清单；这些领域将为项目开发提供初步结构。这项研究完成后，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，采用经典和当代的测试构建和验证方法，包括项目反应理论和计算机化的适应性测试技术。这一试点项目与未来的工作相结合，将通过开发一种有意义的、有效的和简洁的HRQOL测量方法来填补一个重大空白，用于HD临床试验的结果测量。公共卫生相关性：尽管亨廷顿病(HD)基因识别的发展推动了寻找这种致命疾病的有效治疗方法，但目前的评估方法缺乏确定此类治疗对健康相关生活质量(HRQOL)的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患者的HRQOL结果测量方法。这样的指标将与身体功能、情绪功能、参与度和不良事件的指标(如联合亨廷顿病评级量表)一起使用，作为HD临床试验的核心结果指标。

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.