Transcript Neurocognitive Outcomes in Clinical Trials for TSC and Related

Outline
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Significance
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Definitions
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Challenges
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Next steps
Significance
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Quality of Life
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Safety
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Efficacy/potentially modifiable
Definitions
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What is neurocognition?
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Inter-related levels of investigation
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But need to be clear on what we are measuring
What to measure
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Depth vs breadth
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Inclusion criteria (make the most of each trial)
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Across age/ability; validation
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Multi-center: multiple cultures/languages
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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