Development of a Convenient, Automated, Objective Measure of Depression

抑郁症是一种严重的，使人衰弱的疾病，影响数百万人，但治疗研究受到当前结果测量的有限可靠性的阻碍，这些测量通常受到许多方法和临床因素的影响。这些考虑导致发布了计划公告06-016，“开发用于精神健康研究和临床实用的生物标志物”，旨在促进具有临床实用性的创新生物标志物技术的开发，以评估与精神疾病相关的精神功能和功能障碍。PA确定了对生物标志物的“迫切需求”，作为疾病严重程度变化的指标和/或治疗反应的预测因子，可以在个体基础上有效应用。第一阶段SBIR研究成功地建立了计算机自动化评估抑郁症的严重程度，使用全结构化的交互式语音应答系统与患者的互动，并证明了通过语音声学分析通过电话获得的语音样本获得抑郁症的严重程度和治疗反应的有效措施的可行性。由于I期试点研究的成功，医疗技术系统公司成功地说服了一家行业赞助商，将声音声学生物标志物作为探索性措施纳入一项以方法学为重点的随机临床试验。这一开放创造了一个机会，可以更快地推进声乐声学生物标志物研究的发展，如果第二阶段的努力仅仅集中在随机双盲安慰剂对照试验的技术评估上，就像最初设想的那样。第二阶段的工作重点是分析过程的有效自动化，以降低交付成本，复制第一阶段的结果，以进一步验证，技术的普遍扩展，以适用于其他患者群体（非英语人士、儿童/年轻人和老年人），衍生/优化多变量声学模型，以增强生物标志物对治疗反应的敏感性，并预测个体患者的反应可能性。额外的数据收集、分析和结果展示将与马萨诸塞州总医院的抑郁症临床和研究项目合作完成。该产品的商业市场的描述和产品推出的计划概述。重度抑郁症涉及超过60%的自杀，是美国和世界范围内残疾调整生命年的主要原因。临床试验中抑郁症治疗的开发和评估受到不可靠结果测量的阻碍。建立一个有效的，非侵入性的，容易获得的，并概括的抑郁症的严重程度和治疗反应的生物标志物将有助于更好地了解抑郁症和有效的治疗方法的发展。

DESCRIPTION (provided by applicant): Depression is a serious, debilitating disorder that affects millions of people, but treatment research is hampered by the limited reliability of current outcome measures that are often biased by a number of methodological and clinical factors. Such considerations resulted in the issuance of Program Announcement 06-016, "Development of Biomarkers for Mental Health Research and Clinical Utilities" aimed at spurring development of innovative biomarker technologies with clinical utility to assess mental function and dysfunction related to mental illness. The PA identified an "urgent need" for biomarkers as indicators of changes in disorder severity and/or predictors of treatment response that could be effectively applied on an individual basis. Phase I SBIR research successfully established computer-automated assessment of depression severity using fully-structured interactive voice response system interactions with patients and demonstrated feasibility of obtaining valid measures of depression severity and treatment response through vocal acoustic analysis of speech samples obtained over the telephone. As a result of the Phase I pilot study success, Healthcare Technology Systems was successful in persuading an industry sponsor to include vocal acoustic biomarkers as exploratory measures in a methodologically focused randomized clinical trial. This opening creates an opportunity to advance development of vocal acoustic biomarker research faster than would have been possible if Phase II efforts focused solely on technology evaluation in a randomized double-blind placebo controlled trial, as initially envisioned. The Phase II efforts proposed focus on efficient automation of the analytic processes to reduce delivery costs, replication of Phase I results for further validation, generalized extension of the technology for applicability to other patient populations (non-English speakers, children/young adult, and geriatric), and derivation/optimization of multivariate acoustic models to enhance the biomarker sensitivity to treatment response and prediction of the response likelihood for individual patients. The additional data collection, analysis, and presentation of results will be done in collaboration with the Depression Clinical and Research Program at the Massachusetts General Hospital. The product's commercial market is described and a plan for product launch is outlined. Major depression is involved in over 60% of suicides and is a leading cause of disability adjusted life years in the US and worldwide. Development and evaluation of depression treatments in clinical trials is hampered by use of unreliable outcome measures. Establishing a valid, noninvasive, easily obtained, and generalizable biomarker of depression severity and treatment response will contribute to better understanding of depression and development of effective treatments.