PROMIS: Theory to Reality
International Collaboration for Clinical Genomics (iccg)
‘Strategies for Phenotype Data Collection’
May 10, 2013
James Witter MD, PhD FACR
CSO PROMIS
Medical Officer: Rheumatic Diseases
NIH/NIAMS/DSRD
Dynamic Tools to Measure Health Outcomes from the Patient Perspective
Goals of presentation
• General Overview
• The ‘science’ of PROMIS
– Domain theory of disease
– Item Response Theory (IRT)
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• Allows
Testing (CAT)
– Terminology
• Future of PROMIS as phenotyping tool
PROMIS Resources
Informatics
Assessment Center
Supports >100 Studies
Advancing Knowledge
>100 Peer-Reviewed
Publications
Cooperative Group
12 Research Sites
3 Centers
150+ Scientists
Tools
40 Adult Measures
20 Pediatric Measures
Translations
All item banks  Spanish
NIH PROMIS
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Vision-Mission:
• Vision
– The Patient-Reported Outcomes Measurement Information
System (PROMIS®), funded by the National Institutes of
Health, aims to provide clinicians and researchers access to
efficient, precise, valid, and responsive adult- and childreportedto
measures
of health.title style
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• Mission
– PROMIS uses measurement science to create an efficient
state-of-the-art assessment system for self-reported
health.
The Tower of Babel (Brueghel, 1563)
Advancing Patient-Centered Outcomes
PROMIS: A Common Source of PROs
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Clinical Practice
Surveys (CDC)
Clinical research
Clinic
Hospital
NIH
Industry
FDA
Outcomes
• Clinical Outcomes Assessments (COAs)
• PROs: Patient-reported outcomes
• ClinROs: Clinician-reported outcomes
• ObsROs: Observer-reported outcomes
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• all influenced
humanMaster
choices, judgment,
cooperation or
motivation
• Biomarkers
• not influenced by humans
Definitions-Terminology
• Items are questions that have:
• Context, stems, responses
• Parameters (Difficulty, Discrimination)
– Important for analyses, calibration
• Banks (collection of items)
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• “calibrated” on a common metric
– difficulty and discrimination have been estimated
• Define common concept-domain
– Allow computerized adaptive testing (CAT)
• Domains
• Define latent traits/abilities
Item Response Theory
• In psychometrics- body of theory that:
• Describes application of mathematical models to
how people respond to items
» At person and item level
• Serves as basis for measuring
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» Abilities
» Attitudes
• Based on probability of endorsing a particular item
category is function of latent trait or ability
• Ability to improve reliability of instrument
Cycle of Development and
Validation
Qualitative
Research
and Item
Writing of
Concept
Testing
Item
Bank
Analysis
Interpretation
Refining
General Population
Clinical Samples
IRT models Latent Traits:
People and Items are Represented on the Same Scale
Item Difficulty
Are you
able to
get out of
bed.
Are you able to
run 5 miles
Low
High
Low
High
Persons’ Levels of Physical Functi
12
Item Statistics
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DOMAINS
A domain is the specific feeling,
function, or perception you
want to measure.
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Cuts across different diseases
PROMIS® Adult Banks: v1.0
Domains
Emotional Distress – Anger
Emotional Distress – Anxiety
Emotional Distress – Depression
Fatigue
Pain – Behavior
Pain – interference
Physical Function
Satisfaction with Discretionary Social Activities
Satisfaction with Social Roles
Sleep Disturbance
Wake Disturbance (sleep related impairment)
Global Health
Items in
Bank
29
29
28
95
39
41
125
12
14
27
16
Items in
Short
Form
8
7
8
7
7
6
10
7
7
8
8
10
Evolving concept of health
DOMAIN
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DISEASE SPECIFIC
Domains & Diseases: Hypotheses
• Diseases are combinations of different
domains
– fatigue, physical function, anxiety, pain…
• Capturing multiple domains may be
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optimal
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diseases
• Core-common PRO domains are
universally applicable across diseases
(common or rare), ages and ethnicities
Mechanisms
PROs
Interleukins
Phys Fn
Fatigue
Chemokines
Prostaglandins
Social
Sleep
Anxiety
Pain
Fatigue Item Bank
Lower Back
Pain
Depression
Heart Failure
Cancer
COPD
Same metric, same meaning
PROMIS Measures Tested in Six Conditions
Condition
Relevant Item Banks
COPD
Physical Function
Fatigue
Pain
Social Role Satisfaction
Emotional Distress (Depression, Anxiety, Anger)
Heart Failure
Physical Function
Fatigue
Social Role Satisfaction
Depression
Low Back Pain
Pain (Interference and Behavior)
Physical Function
Depression
Fatigue
Sleep Disturbance
Depression
Emotional Distress (Depression, Anxiety, Anger)
Sleep Disturbance
Fatigue
Physical Function
Pain
Arthritis
Physical Function
Cancer
Pain
Fatigue
Emotional Distress (Depression, Anxiety)
Physical Function
The PROMIS Metric
T Score
Mean = 50
SD = 10
Referenced to the US General
Population
PROMIS Fatigue Across Five Clinical Conditions
Cancer
w/ benefit
(2 mos)
N = 310
N = 229
Cancer
Chemo
(B)
Back PainBack Pain Back Pain
(3 mos) (1 mo)
(B)
Depression Depression Depression
(1 mo)
(3 mos)
(B)
N = 114
N = 64
HF Post-transplant
HF Pre-transplant
Exacerbation to Stable
N = 125
COPD Stable (B)
35
40
45
50
55
Average for General Population
COPD Exacerbation (B
60
65
Child-Adult Linkage Studies
• Render child
and adult
editions
comparable
(i.e., same scale)
• Result: life
course outcome
assessment
PROMIS® Pediatric Banks: v1.0
Domains
Emotional Distress – Anger
Emotional Distress – Anxiety
Emotional Distress – Depression
Fatigue
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Pain – Interference
Physical Function-Mobility
Physical Function-Upper Extremity
Peer Relationships
Asthma
title
Items in
Bank
n/a
15
14
23
style
13
125
29
15
17
Items in
Short
Form
6
8
8
10
8
10
8
8
8
PROMIS® Profile Short Forms
(29-43-57 items)
8
6
4
Mental
Anxiety
29
Depression
28
Fatigue
95
Physical
Pain Interference
41
Sleep Disturbance
27
Physical Function
86
Social
Satisfaction with Roles
14
28
28
PROMIS® combines:
• Item Response Theory (IRT) and
Computer Adaptive Testing (CAT)
• Together, IRT and CAT provide precise
measurement
individual
symptoms
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Computerized Adaptive Testing (CAT)
•
Integrates IRT with computers to
administer a PRO instrument
– selects questions on the basis of a patient’s
response to previously administered
questions
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– measurement is “adapted” to individual
– skips uninformative items to minimize
response burden
– allows determination of person’s standing on
a domain without a loss in measurement
precision.
0
50
100
Physical Functioning Item Bank
Item
1
Item
2
Item
3
Item
4
Item
5
Item
6
Item
7
Item
8
Are you able to get in and out of bed?
Are you able to stand without losing your balance for 1 minute?
Are you able to walk from one room to another?
Are you able to walk a block on flat ground?
Are you able to run or jog for two miles?
Are you able to run five miles?
Item
9
Item
n
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Select CATs
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CAT demo results
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What is Assessment Center?
• Web-based research management tool
– Primary mechanism for distribution of PROMIS
instruments
– Display of item- and instrument-level statistics
• Allows
of study-specific
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collection
– Enabled to administer CATs
• Administration of PROMIS and other
instruments
• FREE!!
AC supports different modes of
administration
PROMIS® Scientific Standards
Address:
1) Defining target concept and conceptual model
2) Generating and design of individual items
3) Constructing item pool
4) Determining item bank properties
5) Field testing
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6) Instrument
7) Validity
8) Reliability
9) Interpretability
10)Language translation and cultural adaptation
Contributions: Future Clinical Research
• Precision – improved measurement precision
across the full range of patient-reported
outcomes
• Efficiency – less respondent burden
• Standardization
– more
interpretable
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research with standard terminology and metrics
• International clinical trial applications
• Common language between research and
practice fosters CER