Outline Significance Definitions Challenges Next steps

Significance Quality of Life Safety Efficacy/potentially modifiable

Definitions What is neurocognition? Inter-related levels of investigation But need to be clear on what we are measuring

What to measure Depth vs breadth Inclusion criteria (make the most of each trial) Across age/ability; validation Multi-center: multiple cultures/languages FDA-requirements: clinical vs regulatory significance

Scientific Challenges Drug efficacy –Mouse models: translating from mouse to man –Predicting responders –When and how long to treat Placebo-controlled, double blind trials needed Side effects of drug –Risk/benefits in pediatric population Neurocognitive assessments –Dynamic measures within timeframe of trial –Standard battery across trials

Logistical challenges IRB and FDA requirements Multi-site enrollment for rare disorders Broad Infrastructure –Recruitment, Patient safety, Monitoring, Data management, Data analysis Funding

Next Steps - I Patient Based Outcome Measures In terms of FDA – f/u neuro-onco, epilepsy trials etc. Stratify by epilepsy Younger age/adults/more severely affected Sleep/depression/anxiety

Next Steps - II Off-label use Education- importance of neurocog clinical trials Biomarkers of cognition Funding