The moderate correlation observed between the TAND total score and the metacognition index (MI) of the BRIEF suggested that the TAND Checklist did not fully capture the finer constructs identified by the MI including initiation, working memory, planning or organising and monitoring skills. It was very encouraging that the TAND Checklist executive function subdomain correlated strongly with

all three subscales of the BRIEF. Taken together, results suggest that the TAND Checklist may be very helpful in identifying individuals at risk of potential neuropsychological, and in particular, executive difficulties that would benefit from further evaluation and intervention. The striking finding that almost PD0325901 clinical trial 90% of participants in the study had 6 or more lifetime TAND behavioral difficulties underlined why TAND is such a crucial clinical domain to consider in real life. Further investigations of the lifetime rates across TAND levels of investigation may provide extremely helpful information. In spite of the positive initial findings of this pilot study, it is important to consider potential limitations. This study did not examine reliability of the TAND Checklist such as inter-rater check details or test-retest reliability. It might be very helpful

to examine inter-rater reliability, in particular to see if relatively non-expert clinicians will get similar scores to very experienced TSC clinicians. We predict that the quality of information collected through the TAND checklist will most strongly depend on the quality of the rapport between the interviewer and interviewee. Test-retest reliability is often examined for questionnaires. It is not clear how useful this would be for a TAND Checklist given that new neuropsychiatric manifestations may present over the course of a few weeks to months, thus reducing the likelihood of high stability of measurement. It was outside the scope of this study to examine sensitivity

and specificity of the tool. As raised in the introduction, the purpose of the TAND Checklist was not to generate a ‘diagnostic tool’ with thresholds Celecoxib or ‘cut-off values’ for disorders (see also detail of the conceptualisation of TAND and the TAND Checklist32). For this reason, sensitivity and specificity were not the key considerations in this pilot validation. Further evaluation of other psychometric properties of the TAND Checklist may be natural next steps. Further research is required to replicate and extend investigation of the psychometric properties of the TAND Checklist. Further subsequent validity research studies will help to ascertain whether annual screening of TAND will address the treatment gap of neuropsychiatric disorders.