Down Syndrome (DS) is the most common genetic cause of intellectual disability, with a prevalence of one in 700 births. Clinical trials have attempted to identify DS-specific treatments for intellectual disability as well as for the multiple common DS-associated comorbidities. In clinical research studies, both permission from the participant’s parent (or legal guardian in the case of adults with DS requiring one due to intellectual disability) as well as assent from the participating individual are generally required. Many individuals with DS may not have capacity to make decisions about clinical trial participation, but this has never been investigated. There is an existing knowledge gap as there is a lack of evidence to guide the use of assent for participation in research studies in individuals with DS. Current clinical trials for individuals with DS typically require assent for participation from all participants, which prevents enrollment of individuals unable to provide assent. This may lead to a selection bias for higher functioning individuals with DS. This in turn limits generalizability of results to all individuals with DS, creates a potential ceiling effect for therapies intended to improve cognition and is a barrier to study participation for individuals with DS. The overarching goal of this proposal is to develop an evidence-based framework to guide the approach to assent for individuals with DS to participate in clinical trials. This will be achieved leveraging two existing resources. The first is a survey of a large pool of parents of individuals with DS who are interested in research participation recruited through DS- Connect and the LuMind-IDSC foundation. The second is the use of a validated pediatric tool, the modified MacArthur Competence Assessment Tool for Clinical Research (MacCAT-CR), to determine the ability of individuals with DS to make decisions about participation in clinical research. Specific Aims include: Aim 1: To determine parent/representative preferences for assent to participate in clinical trials in individuals with DS. Aim 2: To determine the capacity of individuals with DS to make decisions about clinical trial participation in a clinic-recruited sample of children and adults with DS.