Decisional Capacity and Informed Consent in Fragile X Syndrome

描述(申请人提供)：脆性X综合征(FXS)是最常见的遗传性智力残疾形式。典型的男性智商在50到55之间。一些人受到严重影响(智商低，不会说话)，而另一些人受到轻微影响(轻度智力障碍，阅读能力，非常善于社交)。女性通常比男性受影响较小，但功能范围更广。少数女性有严重的智力和适应性障碍，但大多数人的智力正常或接近正常；大约三分之一的人有轻微的认知障碍。这种认知能力的广泛范围几乎肯定会导致不同的 选择和独立生活。这项应用侧重于一种特殊形式的选择--决策能力--就是否参与研究做出有意义的决定的能力。患有FXS的人作为研究参与者已经有30多年了。在很大程度上，这项研究是相对非侵入性的，仅限于父母调查和神经心理或心理教育评估。一些研究已经抽取血液、采集唾液、测量心率或使用神经成像，但直到最近，治疗研究一直很少。在过去的3年里，这种情况发生了戏剧性的变化。在了解FXS分子基础方面的进展导致了新一代靶向治疗方法，使用各种化合物的临床试验正在进行中。副作用的可能性以及行为和学习能力发生重大变化的可能性将获得有意义的同意的重要性提升到了一个新的水平。研究人员和IRB成员需要数据来帮助指导有关将FXS患者纳入同意过程的决定。只有几项研究调查了智力和发育障碍个人的决策能力，没有一项研究研究FXS患者。对FXS患者参与研究决策的程度几乎一无所知，也没有研究调查FXS的决策能力。该项目将评估FXS的决策能力范围，确定与决策能力变异性相关的因素，并开发和评估基于平板的决策辅助工具，以帮助获得知情同意。研究团队包括FXS专家、人类研究保护专业人员、为知情决策开发材料的专家、FXS临床试验的领先研究员，以及开发和评估用于表征决策能力的黄金标准措施的研究人员。这项研究将提供有关FXS决策能力性质的重要信息，并将为寻求将FXS患者纳入研究参与者的研究人员、IRB成员和制药公司提供指导。 公共卫生相关性：该项目将首次研究脆性X综合征患者提供知情同意参与研究的能力。鉴于这些患者的临床试验和治疗可能性的出现，了解他们的决定能力对研究人员、临床医生、IRB成员和制药公司将是重要的。该项目将评估FXS的决策能力范围，确定与决策能力变异性相关的因素，并开发和评估基于平板的决策辅助工具，以帮助获得知情同意。

DESCRIPTION (provided by applicant): Fragile X syndrome (FXS) is the most common inherited form of intellectual disability. The typical male has an IQ of 50 to 55. Some are severely affected (low IQ, nonverbal), while others are mildly affected (mild intellectual disabiliy, can read, very sociable). Females are generally less affected than males but have an even broader range in function. A few females have severe intellectual and adaptive impairments, but most have a normal or borderline intellectual ability; about one-third have mild cognitive impairment. This wide range in cognitive ability almost certainly leads to variable ability to make choices and live independently. This application focuses on a particular form of choice making-decisional capacity-the ability to make a meaningful decision about whether to participate in research. Individuals with FXS have served as participants in research studies for more than 30 years. For the most part, this research has been relatively noninvasive, limited to parent surveys and neuropsychological or psycho-educational assessments. Some studies have drawn blood, collected saliva, measured heart rate, or used neuroimaging, but until recently there has been a paucity of treatment research. This scenario has changed dramatically in the last 3 years. Advances in understanding the molecular basis of FXS have led to a new generation of targeted treatment approaches, and clinical trials are underway using a variety of compounds. The possibility of side effects and the potential for significant changes in behavior and learning abilty elevate to a new level the importance of obtaining meaningful consent. Researchers and IRB members need data to help guide decisions about involving individuals with FXS in the consent process. Only a few studies have investigated decisional capacity of individuals with intellectual and developmental disabilities, and none have studied individuals with FXS. Virtually nothing is known about the extent to which individuals with FXS are involved in decisions about research participation, and no studies have investigated decisional capacity in FXS. This project will assess the range of decisional capacity in FXS, identify factors associated with variability in decisional capacity, and develop and evaluate a tablet-based decision aid to assist in obtaining informed consent. The study team includes experts in FXS, human research protection professionals, specialists in developing materials for informed decision making, a leading researcher in FXS clinical trials, and researchers who have developed and evaluated gold-standard measures for characterizing decisional capacity. The study will provide important information about the nature of decisional capacity in FXS and will provide guidance for researchers, IRB members, and pharmaceutical companies seeking to include individuals with FXS as study participants. PUBLIC HEALTH RELEVANCE: This project will be the first to study the ability of individuals with fragile X syndrome to provide informed consent to participate in research. Given the advent of clinical trials and treatment possibilities for these individuals, understanding their decisiona capacity will be important for researchers, clinicians, IRB members, and pharmaceutical companies. This project will assess the range of decisional capacity in FXS, identify factors associated with variability in decisional capacity, and develop and evaluate a tablet-based decision aid to assist in obtaining informed consent.