February 20, 2014 ASENT Annual Meeting, Bethesda, MD Petra Kaufmann MD MSc Director, Office of Clinical Research National Institute of Neurological Disorders and Stroke

Background For many neurological diseases there is no suitable outcome measure for therapeutics development – Properties of measures inadequate for purpose – Methodological robustness varies – Developed for academic research rather than regulatory pathway – Insufficient data available using the measure

Challenges Multiple measures for each domain De novo outcomes development – Redundancy – Lack of comparability Opportunity Build on existing components – Robust methodology – Increased comparability – Less development time and cost

NIH Assessment Tools NIH Toolbox – Assessment of Neurological and Behavioral Function Neuro-QOL – Quality of Life in Neurological Disorders The EXAMINER – Neurobehavioral Evaluation and Research Phen-X – Consensus Measures for Phenotypes and Exposures PROMIS® – Patient-Reported Outcomes Measurement Information System

Joint Adult & Pediatric Measures (self/proctor) Cognition8 Motor6 (peg board) Audition2 Vision1 Olfaction1 Balance1 Somatosensation2 Taste1 PatientObserverClinician Naturalistic Artificial X PROMIS, NeuroQoL Subjective objective

Click to edit Master title style NIH Toolbox for Assessment of Neurological and Behavioral Function Brief, unified set of measures (assessment tool) Multiple indicators of neural and behavioral health functioning –cognitive –emotional –motor –sensory For use in large epidemiological studies and clinical trials

Click to edit Master title style NIH Toolbox for Assessment of Neurological and Behavioral Function Measures the same constructs over lifespan Where possible, objective measures over self- report DOWNSTREAM Could be used as a form of “common currency” across diverse study designs and populations Would maximize yield from large, expensive studies with minimal increment in subject burden and cost

Click to edit Master title style Sensation Motor Cognition Emotion Toolbox Domains

Click to edit Master title style Cognition Working Memory 9 Attention Language Processing Speed Episodic Memory Visual Auditory Executive Function Inhibitory Control Working Memory Cognitive Flexibility Vocabulary Comprehension Reading Decoding

Click to edit Master title style Emotion 10 Positive Affect Negative Affect Stress and Coping Social Relationships Happiness Life Satisfaction Well-Being Sadness Fear Anger General Distress Apathy Perceived Stress Coping Strategy Coping Self-efficacy Social Support Social Network Integration Loneliness

Click to edit Master title style Motor Endurance 11 LocomotionStrengthDexterityBalance Upper Extremity Lower Extremity (Non-vestibular )

Click to edit Master title style Sensation 12 VisionAudition Olfaction Somatosensation Vestibular Balance Taste Auditory Processing Hearing Loss Hearing Threshold Middle Ear Function Vestibular-ocular Reflex Vestibulospinal Function Central Involvement Pain Proprioception Temperature Texture Sensory Feedback Preference Intensity Bitter Perception PROP Sensitivity Odor Identification Olfactory Sensitivity Visual Acuity Function Visual Function HRQL Peripheral Vision

Click to edit Master title style Toolbox Four domain-level batteries Domain batteries to take no more than 30 min to administer; entire Toolbox administration max of 2 hours English and Spanish versions Supplemental set of additional instruments- –Tool Shed

Click to edit Master title style NIH Toolbox Training Manual NIH Toolbox Administration Manual NIH Toolbox Technical Manual NIH Toolbox Scoring and Interpretation GuideNIH Toolbox Scoring and Interpretation Guide NIH Toolbox Accessibility and Accommodations - Quick ReferenceNIH Toolbox Accessibility and Accommodations - Quick Reference Online Resources

Click to edit Master title style Principal Investigator: David Cella, PhD Chair, Department of Medical Social Sciences Director, Center for Patient-Centered Outcomes - Institute for Public Health and Medicine Northwestern University Program Director: Claudia S. Moy, PhD Office of Clinical Research National Institute of Neurological Disorders and Stroke