Developing an Alopecia Areata Disease Activity Index (ALADIN)

描述（由申请人提供）：本申请的目标是开发一种新的结局工具，即有可能用于确定斑秃（AA）临床相关终点的斑秃疾病活动指数（ALADIN）。AA是最常见的自身免疫性疾病之一，终生风险约为2%，仅在美国就影响了530万人，包括所有年龄和种族的男性和女性。AA代表人类脱发的第二种最常见形式，并对受影响的个体造成严重的毁容和心理困扰。AA携带其中一个 在所有皮肤病中，皮肤病的负担最高，特别是在儿童和青少年中，他们的自我形象与他们的外表密切相关。在确定药物疗效和比较AA药物试验的结局时，需要将患者报告的结局（PRO）整合为疾病终点。由于与AA相关的高心理负担，在开发AA新治疗方法时，将患者的观点视为核心结果至关重要。因此，需要开发能够捕捉疾病的情感和心理影响的PRO。据我们所知，AA对患者健康相关生活质量的情绪和心理影响尚未纳入任何已完成的RCT研究。为了将AA特异性PRO纳入疾病进展/状态的评估中，需要存在一种可靠且有效的工具来测量AA临床试验中的一组统一结局。在我们正在哥伦比亚大学医学中心进行的AA临床试验的背景下，我们有独特的机会开发和部署斑秃疾病活动指数（ALADIN）到AA的临床试验中，我们将能够评估其在AA人群中的心理测量特性。ALADIN将通过整合患者报告的健康相关生活质量工具、医生报告的脱发评估、临床测量、基因型风险评分、基因表达分析和血清生物标志物来构建。ALADIN将在广泛接受和广泛验证的克罗恩病活动指数（CDAI）后建模，该指数同样包含患者报告的测量值、医生报告的测量值和生物学数据。我们将应用创新的统计方法开发ALADIN，以创建一个分类器，定量区分疾病状态，预后和治疗反应。最终的工具将是一个单一的指数，可用于监测AA中的疾病活动，并将很容易适应多个临床试验中心，并允许在试验之间进行比较。

DESCRIPTION (provided by applicant): The goal of this application is to develop a new outcome instrument, the Alopecia Areata Disease Activity Index (ALADIN) that has the potential for use in the determination of clinically relevant endpoints for Alopecia Areata (AA). AA is one of the most common autoimmune diseases, with a lifetime risk of approximately 2%, affecting 5.3 million individuals in the United States alone, including males and females of all ages and ethnic groups. AA represents the second most common form of human hair loss, and causes significant disfigurement and psychological distress to affected individuals. AA carries one of the highest burdens among any skin diseases, particularly among children and adolescents whose self-image is so closely linked to their appearance. Integration of patient reported outcomes (PROs) as disease endpoints is needed in the determination of drug efficacy and in the comparison of outcomes across drug trials for AA. Because of the high psychological burden associated with AA, it is essential that the patient's perspective be considered as a core outcome in the development of new treatments for AA. For this reason, PROs need to be developed that can capture the emotional and psychological impact of the disease. To our knowledge, the emotional and psychological impacts of AA on patients' health related quality of life have not yet been included in any completed RCT studies. In order to incorporate an AA specific PRO into the assessment of disease progression/status, there needs to exist a reliable and valid instrument that measures a uniform set of outcomes in clinical trials for AA. In the context of our ongoing clinical trials in AA at Columbia University Medical Center, we have the unique opportunity to develop and deploy the Alopecia Areata Disease Activity Index (ALADIN) into clinical trials for AA, where we will be able to assess its psychometric properties in an AA population. ALADIN will be constructed by integrating a patient reported health-related quality of life instrument; physician reported hair loss assessments, clinical measures, a genotype risk score, and gene expression analysis and serum biomarkers. ALADIN will be modeled after the well-accepted and extensively validated Crohn's disease activity index (CDAI) which similarly contains patient reported measures; physician reported measures, and biological data. We will apply innovative statistical approaches in developing ALADIN, to create a classifier that quantitatively distinguishes disease state, prognosis and therapeutic response. The final instrument will be a single index that can be used to monitor disease activity in AA, and will be easily adaptable to multiple clinical trial sites and allow comparison across trials.