Expressive Language Sampling as an Outcome Measure

描述（由申请人提供）：智力残疾（ID）患者的新治疗方法在本质上越来越具有条件特异性。目前正在进行许多针对脆性X综合征（FXS）和唐氏综合征（DS）的靶向药物的临床试验。特定条件的行为治疗也正在出现。由于缺乏足够的认知和行为终点，所有这些治疗的评估都受到阻碍。在这个项目中，我们建议评估表达性语言采样的充分性，以获得语言相关的临床终点。在这个过程中，表达性语言样本是在高度结构化和脚本化的，但自然的互动中收集的。这些样本可以 分析以得出反映语言技能和非典型语言行为的重要维度的临床终点。尽管表达性语言取样对于FXS或DS临床试验的适用性（或ID更一般）尚未确定，该程序是特别有前途的，因为它们产生临床相关和功能性终点，已被证明可以捕获ID常见的损伤以及FXS或DS特异性的损伤，并已被证明在典型和其他语言障碍人群中产生发育变化的强有力指标。在本研究中，我们提出：（1）检验表达性语言抽样技术所产生的测量结果的基本心理测量学特性，包括建立它们的重测信度、内部一致性、效度和敏感性;（2）评估表达性语言抽样技术的心理测量学特性的差异，作为参与者病因学、年龄、性别、自闭症症状严重程度的变化的函数，和ID水平;（3）比较三种不同的表达性语言采样技术的心理测量学特性;（4）评估在多个站点实施表达性语言采样的可行性，如在典型的临床试验中所要求的。这些目标将通过收集儿童，青少年和年轻人与FXS或DS表达语言样本来解决。样本将在三种互动形式中收集：对话，叙述和结构化互动，包括自闭症诊断观察计划（ADOS）。来自样本的测量将包括那些索引语法（DS中特别严重损害的区域）和持续（FXS中特别严重损害的区域）。将在4周（+/- 1周）时使用替代版本的抽样材料评估重测信度。内部一致性将通过计算抽样技术内部和之间的α系数进行评估。标准化测试和举报人报告将被用作有效性指标。两年的纵向随访将产生对变化敏感性的估计。参与者将在多个地点进行测试，每个地点都在评估FXS或DS患者方面具有相当丰富的经验。将通过在关键指标上比较各地点的语言样本来评估多地点实施的可行性。转录，编码和分析将仅在UC Davis MIND Institute网站进行。

DESCRIPTION (provided by applicant): New treatments for people with intellectual disabilities (ID) are increasingly condition-specific in nature. Numerous clinical trials of targeted pharmacological agents are now in process for fragile X syndrome (FXS) and Down syndrome (DS). Condition-specific behavioral treatments also are emerging. Evaluation of all such treatments is being hampered by a lack of adequate cognitive and behavioral endpoints. In this project, we propose to evaluate the adequacy of expressive language sampling for deriving language-relevant clinical endpoints. In this procedure, expressive language samples are collected in highly structured and scripted, yet naturalistic, interactions. These samples can then be analyzed to derive clinical endpoints reflecting important dimensions of language skill and atypical language behavior. Although the suitability of expressive language sampling for clinical trials with FXS or DS (or ID more generally) has yet to be determined, the procedures are especially promising because they yield clinically relevant and functional endpoints, have been shown to capture impairments that are common to ID as well as those specific to FXS or DS, and have been shown to yield robust indicators of developmental change within typical and other language-impaired populations. In this project, we propose: (1) to examine the basic psychometric properties of measures derived from expressive language sampling techniques, including establishing their test-retest reliability, internal consistency, validity, and sensitiviy; (2) to evaluate differences in the psychometric properties of expressive language sampling techniques as a function of variations in participant etiology, age, gender, autism symptom severity, and level of ID; (3) to compare the psychometric properties of three different expressive language sampling techniques; and (4) to evaluate the feasibility of implementing the expressive language sampling across multiple sites, as would be required in a typical clinical trial. These aims will be addressed by collecting expressive language samples from children, adolescents, and young adults with FXS or DS. Samples will be collected within three interaction formats: conversation, narration, and the structured interactions comprising the Autism Diagnostic Observation Schedule (ADOS). Measures derived from the samples will include those indexing syntax (an area of especially severe impairment in DS) and perseveration (an area of especially severe impairment for FXS). Test-retest reliability will be assessed at 4 weeks (+/- 1 week) using alternate versions of sampling materials. Internal consistency will be assessed by computing alpha coefficients within and across sampling techniques. Standardized tests and informant report will be used as indicators of validity. A two-year longitudinal follow-up will yield an estimate of sensitivity to change. Participants will be tested at multiple sites, each with considerable experience in the evaluation of individuals with FXS or DS. Feasibility of multiple-site implementation will be evaluated by comparing language samples across sites on key indicators. Transcription, coding, and analysis will be conducted only at the UC Davis MIND Institute site.