Clinical Ratings of Neurocognition (CRON)

描述(由申请人提供)：与精神分裂症相关的认知障碍(CIAS)是治疗研究的一个主要焦点，因为它被认为是该综合征的核心特征，与功能结果有关的可靠性高于传统评定的症状。尽管它是当前病理生理学和治疗概念的核心，但对于CIAS还没有公认的临床分级标准。这项拟议的研究将开发和评估一种新的量表：神经认知临床评分(CRON)的可靠性和有效性。CRON将提供：(1)针对CIAS的药物的监管批准可能需要的认知功能障碍严重程度和变化的表面有效测量；(2)关于现实世界认知功能及其与日常生活活动的关系的重要信息，作为标准化认知测试的补充；以及(3)为临床医生提供的新工具，将增强他们对精神分裂症认知缺陷的敏感性，并增加他们对与长期结果和功能残疾更相关的疾病特征的关注。使用CRON的临床医生将根据对患者和护理人员的采访进行评分，抽样NIMH-Matrics共识过程确定的对精神分裂症治疗研究重要的七个神经认知障碍领域。现代心理测量学方法将被用来最大限度地提高Cron对认知障碍的敏感度，并在治疗试验中最有可能针对的范围内发生变化。拟议研究的第一阶段开发了Cron的测试版，使用经典测试理论和项目反应理论方法来提炼一个过度包容的题库，该题库来自于使用第一代工具对210名精神分裂症患者进行的评估，加州大学洛杉矶分校的精神分裂症认知临床全球印象，以及杜克大学的精神分裂症认知评定量表。第二阶段将在一项有288名参与者参与的独立研究中部署CRon，以提供更详细的心理测量学特性评估、评分员间和重测可靠性的初步证据，以及关于神经认知功能的标准化测试、功能能力的代理测量、社区功能测量和使用传统评分表测量的症状的并发和区分效度。建议的发展是迫切需要的，以继续由Matrics倡议建立的势头，并促进监管接受和临床对CIAS新疗法的认识。

DESCRIPTION (provided by applicant): Cognitive impairment associated with schizophrenia (CIAS) is a major focus of treatment research because it is acknowledged as a core feature of the syndrome that is more reliably associated with functional outcomes than traditionally rated symptoms. Despite its centrality to current concepts of pathophysiology and treatment, there are no accepted clinical rating scales for CIAS. The proposed research will develop and assess reliability and validity of a new scale: Clinical Ratings of Neurocognition (CRON). CRON will provide: (1) face-valid measures of severity and change of cognitive dysfunction that will likely be needed for regulatory approval of agents targeting CIAS; (2) important information about real-world cognitive functioning and its relations to activities of daily living, complementing standardized cognitive tests; and (3) a new tool for clinicians that will enhance their sensitivity to cognitive deficits in schizophrenia, and increase their attention to features of the illness more relevant to long-term outcome and functional disability. Clinicians using CRON will base their ratings on interviews of patients and caregivers, sampling the seven domains of neurocognitive impairment important for schizophrenia treatment research as determined by the NIMH- MATRICS consensus process. Modern psychometric methods will be used to maximize CRON's sensitivity to cognitive impairment and change over the range most likely to be targeted in treatment trials. Phase 1 of the proposed research develops a beta version of CRON, using Classical Test Theory and Item Response Theory methods to refine an over-inclusive item-bank derived from assessments completed in 210 people with schizophrenia using first-generation instruments, the Clinical Global Impression of Cognition in Schizophrenia from UCLA, and the Schizophrenia Cognition Rating Scale from Duke. Phase 2 will deploy CRON in an independent study of 288 participants, to provide more detailed assessment of psychometric properties, preliminary evidence of inter-rater and test-retest reliability, and concurrent and discriminant validity with respect to standardized tests of neurocognitive function, proxy measures of functional capacity, measures of community function, and symptoms measured with traditional rating scales. The proposed developments are urgently needed to continue the momentum established by the MATRICS initiative, and facilitate regulatory acceptance and clinical awareness of new treatments for CIAS.