Including the Patient’s Voice February 20, 2014 David Cella, PhD Professor and Chair Department of Medical Social Sciences Northwestern University Feinberg School of Medicine American Society for Experimental NeuroTherapeutics | 16 th Annual Meeting

Disclosure National Institutes of Health Grantee American Society for Experimental NeuroTherapeutics | 16 th Annual Meeting

Learning Objectives 1)Understand the options that ensure the content validity and patient-centeredness of questions that get included into patient-reported clinical trial data 2)Be familiar with the family of NIH-sponsored person-centered outcome measures a)PROMIS b)Neuro-QoL c)NIH Toolbox American Society for Experimental NeuroTherapeutics | 16 th Annual Meeting

Distinguishing PROs from Other Assessments 5 Patient-reported outcome (PRO) Standardized assessment based on patient self-report, completed alone (Examples: SF-36; PROMIS; Neuro-QoL; Toolbox Emotion; MSQLI; PDQ-39) ClinRO Assessment based on physician interpretation of patient status (Examples: Ham-D, Karnofsky; EDSS; Rankin/mRS) Performance-based assessment Objective test measuring patient performance (Examples: reaction time, 6MWT, FEV 1 ; Toolbox Motor, Sensory and Cognition) Clinical assessment Based on clinical examination and diagnostic evaluation (Examples: disease stage; histology; pathology; EEG; radiography) 5

“Performance Measure” “Self report” Both provide information, r = 0.40

Content Validity: Content Consensus through Qualitative Research ISPOR Task Force on Content Validity of Existing Instruments. Value in Health (Figure 2) Instrument Evaluation (Cognitive Interviews) Concept Elicitation (Focus Groups & Interviews) Generated Words & Phrases Interpretation & Meaning Consensus Wording Items & Response Options Developer Expertise Structure Recall, Instructions Format 7

What is Saturation?  Defined as “Data adequacy”  Operationalized as “collecting data until no new information is obtained” Glaser and Strauss (1967)  “Boredom that occurred when investigators had ‘heard it all’” – Margaret Mead

Rule of Thumb for Number of Interviews Bertaux (1981) - 15 is the smallest acceptable sample size in qualitative research. Kuzel (1992) interviews for a homogeneous sample and data sources “when looking for disconfirming evidence or trying to achieve maximum variation.” Morse (1994) - at least 6 participants for phenomenological studies, and 35 participants for ethnographies, grounded theory studies, and ethno-science studies Creswell (1998) interviews for a phenomenological study and for a grounded theory study. Bernard (2000) - most ethnographic studies are based on 36 interviews Guest et al (2006) – conducted 60 interviews and achieved saturation by 12 None of these sources except Guest provided any evidence for their recommendations

Rule of Thumb for Number of Focus Groups Vaughan et al. (1996) – 3-4 focus groups per any defined group

Establish - target population - scope of assessment - concepts to include - available resources Develop items based on - literature review - focus groups - in-depth interviews Evaluate psychometric properties Pilot test candidate instrument Revise and finalize instrument Evaluate cross-cultural equivalence Pretest in sample of target population Item reduction *Note: The sequence of steps may vary Construction of a PRO Instrument: an Iterative Process*

 All endpoints require thoughtful development and proper validation.  Review medical and health services research literature  Review various PRO bibliographies/websites/guides  Select instruments that best match relevant domains –Sensitivity of measurement –Coverage of domains  Align endpoints chosen with clinical trial population and endpoint model Planning for PRO Assessment in a Clinical Trial 12

I’m worried and concerned Bloating bothers me! I can’t bend over or exercise I hate my life Heartburn disturbs my sleep I can’t eat and drink whatever I like

14 PROMIS Cooperative Group Highlights 50 protocols aligned with evolving PROMIS standards 50,000 people have contributed data 2,000 in qualitative research 45,000 in quantitative research 15,000 children 3,000 adult proxies for children 30,000 adults on their own behalf …including more than 5,000 Spanish-speaking adults and children

15 PROMIS Domain Framework

16 Testing General Population Clinical Samples AnalysisInterpretationRefining QualitativeResearch and Item Writing Item Bank Cycle of Development and Validation

17 The PROMIS Metric T Score Mean = 50 SD = 10 Referenced to the US General Population

18 PROMIS Basic Tools Derived from Item Banks Computerized Adaptive Testing (CAT)  Dynamic testing averaging 6 items per domain Fixed Length Forms  By individual domain (8-10 items)  By health profile (-29, -43, -57) Global Health Index

Neurological Outcomes Beyond Mobility It’s important to be able to walk to the store. It’s also important to remember why you did. Also important to manage finances, maintain a household, plan social events, sexual function QoL, etc.) Are the important things measured by the usual outcome tools? 20

NINDS-funded initiative Use in chronic neurologic conditions Can be administered as CATs or short forms Most scores can be linked to PROMIS Neuro-QoL: PRO Measures for Neurology Research and Practice

Neuro-QoL Domain Framework Self-Reported Health Social Health Mental Health Physical Health Symptoms Function Emotional Health Cognitive Health

Delirium as a model for a factor affecting specific domains Mobility hardly different, applied cognition very different. 25 Delirium retrieved from EDW and charted bedside assessments (~2400 assessments in ~100 pts)

26 What it is: What it is not:  Brief unified set of measures  Use in large longitudinal, epidemiological, clinical trials  Measures the same constructs over lifespan  Where possible, objective measures over self-report  Not a diagnostic tool  Not conceptualized to substitute for the in- depth assessment of a domain or sub-domain

Sensory Motor Cognition Emotion Toolbox Domains

Working Memory 28 Attention Language Processing Speed Cognition Episodic Memory Visual Auditory Executive Function Inhibitory Control Working Memory Cognitive Flexibility Vocabulary Comprehension Reading Decoding

Emotion 29 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

Endurance 30 LocomotionStrengthDexterityBalance Motor Upper Extremity Lower Extremity (Non-vestibular )

Sensation 31 VisionAudition Olfaction Somatosensation Vestibular Balance Taste Auditory Processing Hearing Loss Hearing Threshold Middle Ear Function Vestibularocular 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

NIH-sponsored Resource Comparisons Neuro-QOLPROMISNIH Toolbox Disease Area(s) NeurologyNon-specific Respondent Self, Proxy Self, Proxy, Proctor Administered Domains Physical Mental Social …self-reported health Physical Mental Social …self-reported health Emotional Health Motor Function Cognitive Function Sensory Function Languages - current English, SpanishEnglish, Spanish, othersEnglish, Spanish Languages - future Many

33 I FOUND OPTIONS. HOW DO I CHOOSE?

34 How do I select an instrument? There is no simple formula or algorithm – Research is needed – Consultation can help Identify participant age group (pediatric vs adult) Select language(s) Select relevant domains Select mode of administration (paper, web, offline computer, interview)

35 Instrument Selection What disease/condition? – Expected range? Why are you capturing PROs? – Need for label claim? – Clinically meaningful change? – Desire to cover specific content? Assess need for brevity versus precision – Expected change? Assess available reliability and clinical validation data

Impact on Clinical Care and Practice There are several patient-centered outcome tools ready for clinical and research use. Many are freely available All were developed with patient-centric or person-centric methods. Domain content is abundant Precise, valid measurement is possible without burdening patients Further work can enhance clinical utility

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