Rare Diseases and PROMIS: Opportunities Natcher Conference Center

March 1, 2013

James Witter MD, PhD FACRCSO PROMIS

Medical Officer: Rheumatic DiseasesNIH/NIAMS/DSRD

Rare Diseases and PROMIS: Opportunities Natcher Conference Center

March 1, 2013

James Witter MD, PhD FACRCSO PROMIS

Medical Officer: Rheumatic DiseasesNIH/NIAMS/DSRD

Dynamic Tools to Measure Health Outcomes from the Patient Perspective

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Goals of presentation

• General Overview

• The ‘science’ of PROMIS– Domain theory of disease– Item Response Theory (IRT)

• Application of Computerized Adaptive Testing (CAT)

– Terminology

• Future in rare diseases

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Definitions-Terminology

• Items are questions that have:• Context, stems, responses• Parameters (Difficulty, Discrimination)

– Important for analyses, calibration

• Banks (collection of items) • “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

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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 » Abilities» Attitudes

• Based on probability of endorsing a particular item category is function of latent trait or ability

• Ability to improve reliability of instrument

Low High

Persons’ Levels of Physical Function

Item Difficulty

IRT models Latent Traits:People and Items are Represented on the Same Scale

Are you able to run 5 miles

Are you able to

get out of bed.

Low High

5

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DOMAINS

A domain is the specific feeling, function, or perception you want to measure.

Cuts across different diseases

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Evolving concept of health

DOMAIN

vs. DISEASE SPECIFIC

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Domains & Diseases: Hypotheses

• Rare diseases are combinations of different domains– fatigue, physical function, anxiety, pain…

• Capturing multiple domains may be optimal way to assess rare diseases

• Core-common PRO domains are universally applicable across diseases, ages and ethnicities

• Core PRO domains can link common and rare diseases

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Outcomes (FDA workshop & ICOAWG)

• Clinical Outcomes Assessments (COAs)

•PROs: Patient-reported outcomes

•ClinROs: Clinician-reported outcomes

•ObsROs: Observer-reported outcomes

• all influenced by human choices, judgment, cooperation or

motivation

• Biomarkers• not influenced by humans

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Patient-Reported Outcomes (PROs)

• FDA and NIH recognize PROs as important outcomes to answer clinical questions– translating the efficacy-effectiveness and

safety of therapeutics• In development (clinical research)• In the real world (clinical care)

• Patient burden is important aspect of PRO assessment in both these settings

The Tower of Babel (Brueghel, 1563)

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Advancing Patient-Centered Outcomes

PROMIS: A Common Source of PROsPROMIS: A Common Source of PROs

Clinical PracticeClinical research

Surveys (CDC)

NIH FDA

Clinic Hospital

Industry

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NIH PROMIS

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PROMIS: Present

PROMIS Resources

Advancing Knowledge>100 Peer-Reviewed

Publications

InformaticsAssessment CenterSupports >100 Studies

Tools40 Adult Measures

20 Pediatric Measures

TranslationsAll item banks Spanish

Cooperative Group12 Research Sites

3 Centers150+ Scientists

DOMAINS

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Common DOMAINS

• Fibromyalgia•Pain, fatigue, depression

• SLE•Fatigue, pain, social function

• RA•Pain, physical function, fatigue

Anxiety

Prostaglandins

Interleukins

Chemokines

Sleep

PROsPROsMechanismsMechanisms

Pain

Phys Fn

SocialFatigue

Fatigue Item Bank

Lower Back Pain

Same metric, same meaning

Depression

Heart Failure

Cancer

COPD

PROMIS Measures Tested in Six ConditionsCondition Relevant Item Banks

COPD Physical FunctionFatiguePainSocial Role Satisfaction Emotional Distress (Depression, Anxiety, Anger)

Heart Failure Physical FunctionFatigueSocial Role SatisfactionDepression

Low Back Pain Pain (Interference and Behavior)Physical FunctionDepressionFatigueSleep Disturbance

Depression Emotional Distress (Depression, Anxiety, Anger)Sleep DisturbanceFatiguePhysical FunctionPain

Arthritis Physical Function

Cancer PainFatigueEmotional Distress (Depression, Anxiety)Physical Function

The PROMIS Metric

T ScoreMean = 50

SD = 10

Referenced to the US General Population

5035 40 45 55 60 65

PROMIS Fatigue Across Five Clinical Conditions

Average for General Population

COPD Stable (B) COPD Exacerbation (B)

HF Pre-transplantHF Post-transplant

Exacerbation to Stable

Depression (B)

Depression (1 mo)

Depression(3 mos)

Cancer Chemo

(B)

Cancer w/ benefit(2 mos)

Back Pain(B)

Back Pain(1 mo)

Back Pain(3 mos)

N = 64

N = 310

N = 114

N = 229

N = 125

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27

PROMIS® Profile Short Forms (29-43-57 items)

27

Anxiety29Anxiety29

Depression28Depression28

Fatigue95Fatigue95

Pain Interference41Pain Interference41

Sleep Disturbance27Sleep Disturbance27

Physical Function86Physical Function86

Satisfaction with Roles14Satisfaction with Roles14

46

8

Mental

Physical

Social

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PROMIS® combines:

• Item Response Theory (IRT) and Computer Adaptive Testing (CAT)

• Together, IRT and CAT provide precise measurement of 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

• 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.

Computerized Adaptive Tests

0011

2233

- 1

- 1

- 2

- 2

- 3

- 3

high high physicalphysicalfunctionfunction

0011

22

Question #2Question #2

1122

Question #3Question #3

QuestionnaireQuestionnairewith a highwith a highprecision -precision -

ANDAND a awide rangewide range

lowlowphysicalphysicalfunctionfunction

Question #1Question #1

Who uses CAT?

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• Covers the whole range of the domain• Items are “calibrated” (difficulty and

discrimination)

CAT Starts with an Item Bank

An item bank is a large collection of items measuring a single domain.

Any and all items can be used to provide a score for that domain.

PROMIS® Adult Banks: v1.0

DomainsDomains

Items Items inin

BankBank

Items in Items in ShortShortFormForm

Emotional Distress – AngerEmotional Distress – Anger 2929 88Emotional Distress – Anxiety Emotional Distress – Anxiety 2929 77Emotional Distress – Depression Emotional Distress – Depression 2828 88FatigueFatigue 9595 77Pain – Behavior Pain – Behavior 3939 77Pain – interferencePain – interference 4141 66Physical FunctionPhysical Function 125125 1010Satisfaction with Discretionary Social Satisfaction with Discretionary Social

ActivitiesActivities1212 77

Satisfaction with Social RolesSatisfaction with Social Roles 1414 77Sleep Disturbance Sleep Disturbance 2727 88Wake Disturbance (sleep related Wake Disturbance (sleep related

impairment)impairment)1616 88

Global HealthGlobal Health 1010

Child-Adult Linkage Studies

• Render child and adult editions comparable (i.e., same scale)

• Result: life course outcome assessment

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DomainsDomains

Items Items inin

BankBank

Items in Items in ShortShortFormForm

Emotional Distress – AngerEmotional Distress – Anger n/an/a 66

Emotional Distress – Anxiety Emotional Distress – Anxiety 1515 88

Emotional Distress – Depression Emotional Distress – Depression 1414 88

FatigueFatigue 2323 1010

Pain – Interference Pain – Interference 1313 88

Physical Function-MobilityPhysical Function-Mobility 125125 1010

Physical Function-Upper ExtremityPhysical Function-Upper Extremity 2929 88

Peer Relationships Peer Relationships 1515 88

AsthmaAsthma 1717 88

PROMIS® Pediatric Banks: v1.0

Assessment Centerwww.nihpromis.org

- Download PROMIS questionnaires- Computerized Adaptive Tests -Study-specific URL- Non-PROMIS items- eConsent- Data dumps- NIH inclusion enrollment report

AC supports different modes of administration

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Select CATs

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CAT demo results

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Contributions: Future Clinical Research

• Precision – improved measurement precision across the full range of patient-reported outcomes

• Efficiency – less respondent burden

• Standardization – more interpretable research with standard terminology and metrics

• International clinical trial applications

• Common language between research and practice fosters CER

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Rare Diseases: Opportunities

There are estimated to be 7000

rare diseases

There are not 7000 PRO

instruments to measure them