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