Assessment of Fatigue:Assessment of Fatigue:Review and Future DirectionsReview and Future Directions

Zeeshan Butt, Ph.D.Zeeshan Butt, Ph.D.Research Scientist, Center on Outcomes, Research, and Education (CORE)/ENHResearch Scientist, Center on Outcomes, Research, and Education (CORE)/ENH

Research Assistant Professor, Northwestern University Feinberg School of MedicineResearch Assistant Professor, Northwestern University Feinberg School of Medicinez-butt@northwestern.eduz-butt@northwestern.edu

AGS/NIA/Hartford Conference: Idiopathic Fatigue of AgingAGS/NIA/Hartford Conference: Idiopathic Fatigue of AgingSeptember 5, 2008September 5, 2008

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OverviewOverview

Self-reportSelf-report

Fatigue measurementFatigue measurement

Existing instrumentsExisting instruments

Future directions: PROMISFuture directions: PROMIS

FatigueFatigue

Clinically important, but non-specific Clinically important, but non-specific symptom symptom

present across a number of chronic present across a number of chronic illnesses illnesses and health conditionsand health conditions

Given the subjective nature of fatigue, self-Given the subjective nature of fatigue, self-reportreport may be the best way to assess the may be the best way to assess the symptom.symptom.

Fatigue Self-reportFatigue Self-report

Subjective nature suggests reliance on self-Subjective nature suggests reliance on self-reportreport

Several validated tools exist for measuring Several validated tools exist for measuring fatiguefatigue no instrument is the clear gold-standard methodno instrument is the clear gold-standard method

Many instruments tend to assess fatigue as Many instruments tend to assess fatigue as multidimensional conceptmultidimensional concept dimensions: dimensions: temporal characteristics, severity, impacttemporal characteristics, severity, impact manifestations: manifestations: physical, cognitive, emotional, behavioralphysical, cognitive, emotional, behavioral

Multidimensional ScalesMultidimensional Scales

Fatigue Assessment InstrumentFatigue Assessment Instrument Fatigue Impact ScaleFatigue Impact Scale Fatigue Symptom InventoryFatigue Symptom Inventory Multidimensional Assessment of Fatigue Multidimensional Assessment of Fatigue

and the Global Fatigue Indexand the Global Fatigue Index Multidimensional Fatigue InventoryMultidimensional Fatigue Inventory Multidimensional Fatigue Symptom InventoryMultidimensional Fatigue Symptom Inventory Piper Fatigue ScalePiper Fatigue Scale

Revised Piper Fatigue Scale Revised Piper Fatigue Scale (PFS)(PFS)

SubscaleSubscaleBehavioral/Behavioral/severityseverity(6 items)(6 items)

Affective meaningAffective meaning(5 items)(5 items)

SensorySensory(5 items)(5 items)

Cognitive/moodCognitive/mood(6 items)(6 items)

22 items with 4 subscales

Sample Question“To what degree is fatigue you are feeling now causing you distress?” (0=no distress, 10=great deal of distress)

“To what degree would you describe fatigue which you are experiencing now as being:” (0=pleasant, 10=unpleasant)

“To what degree are you now feeling:” (0=lively, 10=listless)

“To what degree are you now feeling:” (0=able to think clearly, 10=unable to think clearly)

Piper et al. Oncol Nurs Forum. 1998;25:677-684.

Fatigue Symptom Inventory Fatigue Symptom Inventory (FSI)(FSI)

DimensionDimensionIntensityIntensity(4 items)(4 items)

InterferenceInterference(7 items)(7 items)

DurationDuration(2 items)(2 items)

Daily patternDaily pattern(1 item)(1 item)

14 items assessing 4 dimensions

Sample Question“Rate your level of fatigue on the average in the last week” (0=not at all fatigued, 10=as fatigued as could be)

“Rate how much, in the past week, fatigue interfered with your normal work activity” (0=no interference, 10=extreme interference)

“Indicate how much of the day, on average, you felt fatigued in the past week” (0=none of the day, 10=the entire day)

“Indicate which of the following best describes the daily pattern of your fatigue” (0=not fatigued, 1=worse in morning, 2=worse in afternoon, 3=worse in evening, 4=no consistent pattern)

Hann et al. Qual Life Res. 1998;7:301-310.

Fatigue MeasurementFatigue Measurement Many instruments tend to assess fatigue Many instruments tend to assess fatigue

as a multidimensional conceptas a multidimensional concept

BUT, there BUT, there may be little may be little difference in difference in scores scores produced by produced by items rated items rated for intensity for intensity vs. vs. frequencyfrequency

Chang, Cella et al, 2003, Palliat Supp Care

Fatigue MeasurementFatigue MeasurementAND results of bi-factor analysis suggests that fatigue AND results of bi-factor analysis suggests that fatigue measurement is sufficiently unidimensionalmeasurement is sufficiently unidimensional

Lai et al, 2006, Qual Life Res

THIS IS GOOD

NEWS!!!(stay tuned)

Single-ItemSingle-ItemAssessmentsAssessments

Single-Item AssessmentsSingle-Item Assessments

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Not at all A little bit Somewhat Quite a bit Very much

I have a lack of energy

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Butt et al., 2008, JNCCN

Greater levels of fatigue associated with worse overall health-related quality of life, F(4, 524) = 70.88, p < 0.0001.

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Fatigue Pain Anxiety Depression Appetite Loss

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False Positive

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False Positive

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False Positive

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False Positive

AUC = 0.76AUC = 0.71 AUC = 0.88 AUC = 0.68 AUC = 0.86

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False Positive

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False Positive

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False Positive

AUC = 0.76AUC = 0.71 AUC = 0.88 AUC = 0.68 AUC = 0.86

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Single-Item AssessmentsSingle-Item Assessments

Butt et al., 2008, JPSM

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False Positive

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False Positive

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False Positive

AUC = 0.76AUC = 0.71 AUC = 0.88 AUC = 0.68 AUC = 0.86

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False Positive

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False Positive

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False Positive

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False Positive

AUC = 0.76AUC = 0.71 AUC = 0.88 AUC = 0.68 AUC = 0.86

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Unidimensional ScalesUnidimensional Scales

Brief Fatigue InventoryBrief Fatigue Inventory Fatigue Severity ScaleFatigue Severity Scale Functional Assessment of Chronic Illness Therapy – Functional Assessment of Chronic Illness Therapy – Fatigue Fatigue Global Vigour and AffectGlobal Vigour and Affect Schedule of Fatigue and AnergiaSchedule of Fatigue and Anergia

Brief Fatigue Inventory (BFI)Brief Fatigue Inventory (BFI)

Your fatigue right NOWYour level of fatigue during

the past 24 hoursUsualWorst

How much, during the past24 hours, fatigue hasinterfered with:

General activityMoodWalking abilityNormal workRelations with other people

Mendoza et al. Cancer. 1999;85:1186-1196.

Please rate: No fatigueAs bad as

you can imagine

Does not interfere

Completelyinterferes

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0 1 2 3 4 5 6 7 8 9 100 1 2 3 4 5 6 7 8 9 10

Sample FACIT-F Subscale Sample FACIT-F Subscale ItemsItems

Fatigue componentFatigue component I feel fatiguedI feel fatigued I feel weak all overI feel weak all over I feel listless I feel listless

(“washed out”)(“washed out”)

Response format

0 = Not at all

1 = a little bit

2 = somewhat

3 = quite a bit

4 = very much

Yellen et al. J Pain Symptom Manage. 1997;13:63-74.

FACIT-FatigueFACIT-FatigueExamplesExamples

Fatigue in Men and Women over Fatigue in Men and Women over 5050

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Degree of Fatigue

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cancer - woman under 50 (N=271) cancer - men under 50 (N=118)cancer - women 50 and over (N=1115) cancer - men 50 and over (N=773)general - women under 50 (N=310) general - men under 50 (N=324)general - women 50 and over (N=209) general - men 50 and over (N=163)

Cella et al., 2002, Cancer

Fatigue Across the LifespanFatigue Across the Lifespan

Butt et al., under review

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MOREfatigue

Across both groups, there was evidence for increased fatigue with age (F(6, 1797) = 3.53, p < 0.01) but no group x age interaction (p > 0.25).

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Phase 1

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Note: Minimally important difference on the FACIT Fatigue subscale is 3 points.

Phase 2

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10.6 (Hb)

13.1 (Hb)

13.3 (Hb)

10.8(Hb)

10.8 (Hb) 10.9 (Hb)

13.1(Hb)Δ Fatigue = -6.1

Δ Fatigue = 4.8

Δ Fatigue = 9.5

Δ Fatigue = 3.9

Group 1 (EPO, n=32 Placebo, n=30)

Group 2 (Placebo, n=26 EPO, n=24)

Changes in Hemoglobin and Changes in Hemoglobin and FatigueFatigue

Agnihotri, Telfer, Butt, et al. (2007) JAGS

FACIT-F, SF-36 and MAF FACIT-F, SF-36 and MAF in RA anti-TNF Trial (N=625)in RA anti-TNF Trial (N=625)

Cella et al., 2005, J Rheumatol

PROMISPROMIS

PROMISPROMIS

““The NIH Patient-Reported Outcomes The NIH Patient-Reported Outcomes Measurement Information System Measurement Information System (PROMIS) Roadmap initiative is a 5-year (PROMIS) Roadmap initiative is a 5-year cooperative group program of research cooperative group program of research designed to develop, validate, and designed to develop, validate, and standardize item banks to measure standardize item banks to measure patient-reported outcomes (PROs) that are patient-reported outcomes (PROs) that are relevant across common medical relevant across common medical conditions.”conditions.”

http://www.nihpromis.org

Broad ObjectivesBroad Objectives

Develop and test a large bank of items Develop and test a large bank of items measuring PROs, including fatiguemeasuring PROs, including fatigue

Create a CAT for efficient assessment of Create a CAT for efficient assessment of PROs across a range of chronic diseasesPROs across a range of chronic diseases

Create a publicly available, adaptable and Create a publicly available, adaptable and sustainable system allowing clinical sustainable system allowing clinical researchers access to a common item researchers access to a common item repository and CATrepository and CAT

ADL – Activities of Daily LivingIADL – Instrumental Activities of Daily LivingG – Global Item

Satisfaction

Satisfaction

Satisfaction

Satisfaction

Performance

G Symptoms

G Activities: Instrumental Activities of Daily Living

[IADL] (e.g. errands)

Other

Social Support

G Anxiety

G Anger/Aggression

G Depression

G Fatigue

G Substance Abuse

Positive Psychological Functioning

Negative Impacts of Illness

Subjective Well-Being (positive affect)

Positive Impacts of Illness

Meaning and Coherence (spirituality)

G Emotional Distress

Mastery and Control (self-efficacy)

Cognitive Function

G Central: neck and back (twisting, bending, etc)

G Lower Extremities: walking, arising, etc [mobility]

G Upper Extremities: grip, buttons, etc [dexterity]

G Function/Disability

G Physical Health

G Mental Health

G Social Health

Satisfaction

G Health

G Pain [intensity, duration, frequency, interference, affect]

Patient-Reported Outcomes (PROs)Preliminary PROMIS Domains shaded

G Role Participation

Item Reduction –Item Response Theory (IRT)

QuantitativeProcesses

Computerized Adaptive Testing

(CAT)

Final Domain MappingUnidimensionality

Adoption and Dissemination

Development of“Short Forms”

Domain Hierarchy

Exhaustive Item Banking –All Available Questions

Item Reduction – Qualitative Item Review

Item Reduction – Patient Input

Item Improvement – Clarity, Floors, Ceilings,Response

Categories, New Items

QualitativeProcesses

Validation – Responsiveness – Internet and Devices

PROMIS ProcessPROMIS Process

Items fromItems fromInstrumentInstrument

AA

Item PoolItem Pool Evaluated by expert and patient review, focus groups, cognitive testing

Items fromItems fromInstrumentInstrument

BB

Items fromItems fromInstrumentInstrument

CC

NewItems

Item BankItem Bank(IRT-calibrated items reviewed forreliability, validity, and sensitivity)

ItemItemResponseResponseTheoryTheory(IRT)(IRT) 0.0

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QuestionnaireQuestionnaireadministered to largerepresentative sample

CATCATShort FormShort FormInstrumentsInstruments

IRTIRT Item Response Theory (IRT) models enable Item Response Theory (IRT) models enable

reliable and precise measurement of PROsreliable and precise measurement of PROs

Fewer items needed for equal precisionFewer items needed for equal precision Making assessment brieferMaking assessment briefer

More precision gained by adding itemsMore precision gained by adding items Reducing error and sample size requirementsReducing error and sample size requirements

Error is understood at the individual levelError is understood at the individual level

Enabling Enabling practicalpractical individual assessment individual assessment

Proficiency of a Fatigue IBProficiency of a Fatigue IBItems

(response category measure)Patients

(frequency distribution) 6.61

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Mean=-1.00 1.22Median = -1.03

Mean= 0.55 1.89Median = 0.29

Fatigue (in logits)

High perf response categoriesPeople with low fatigue

Count Count

Ceiling effect (7/301=2.3%)

Gap (4.2 – 4.8)

People with high fatigue Low perf response categories

Uses for Item BanksUses for Item Banks

Emotional Distress

Pain

Fatigue Item Bank—Item40—Item38—Item36—Item34—Item32—Item30—Item28—Item26—Item24—Item22—Item20—Item18—Item16—Item14—Item12—Item10—Item8—Item6—Item4—Item2

Short Forms

•5-7 Items in each HRQL Area

•Constructed to cover full range of trait

OR

•Multiple forms constructed to only cover a narrow range of trait (eg., high, medium, or low)

Computerized Adaptive Testing (CAT)

•Custom individualized assessment

•Suitable for clinical use

•Accuracy level chosen by researcher

ProstateCancer

—Item40—Item38

—Item34—Item32

—Item26

—Item 22

—Item 18—Item 16

—Item 8

—Item 2

BreastCancer

—Item 36—Item 34—Item 32

—Item 28—Item 26

—Item 22

—Item 14

—Item 10

—Item 2

BrainTumor

—Item 40

—Item 32

—Item 24

—Item 16

—Item 8•3 Diseases

•3 Trials

•3 Unique Instruments

• Each based on content interest of individual researchers

Item Selection

Gershon et al, Exp Rev Pharmoecon Outcomes Res. (2003)

CAT Simulation - FatigueCAT Simulation - Fatigue

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Item Meas SE

QuestionQuestion ResponseResponse

1. I have a lack of energy.1. I have a lack of energy. Very muchVery much

2. I have had enough energy to eat.2. I have had enough energy to eat. Most of the timeMost of the time

3. I have had enough energy to take a bath or 3. I have had enough energy to take a bath or shower.shower.

Some of the Some of the timetime

4. I have had enough energy to read.4. I have had enough energy to read. Some of the Some of the timetime

5. I have had enough energy to leave the house.5. I have had enough energy to leave the house. Most of the timeMost of the time

Fatigue Measure and Standard Error Comparision by Test Length

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5 Item CAT 10 Item CAT 72 Item Bank 6 Item SF 13 Item Scale

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7-item Short-form7-item CAT

Full-length item Bank

No Fatigue Severe Fatigue

SE=0.32 (r=0.90)

SE=0.22 (r=0.95)

Comparison of Measurement PrecisionFull-length Item Bank vs. CAT vs. Short-form

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Short Form -- High End (i.e., severe fatigue)

Short Form – Lower End (i.e., no/mild fatigue)

Short Form – Cover the whole fatigue continuum

Precision Comparison: 3 short-forms

PROMISPROMIS

……is a fully encompassing replacement for is a fully encompassing replacement for existing instrumentsexisting instruments

...allows cross-walk to FACIT-Fatigue, SF-...allows cross-walk to FACIT-Fatigue, SF-36 vitality, etc.36 vitality, etc.

……offers flexibility to researchersoffers flexibility to researchers

ConclusionsConclusions Fatigue is best assessed by self-report.Fatigue is best assessed by self-report.

Many instruments assess fatigue as a multi-Many instruments assess fatigue as a multi-dimensional conceptdimensional concept

Fatigue is sufficiently unidimensional, from a Fatigue is sufficiently unidimensional, from a measurement perspective.measurement perspective.

This measurement property allows for IRT-This measurement property allows for IRT-based measurement applications.based measurement applications.

ConclusionsConclusions PROMIS allows for flexible assessment of PROMIS allows for flexible assessment of

fatigue with use of psychometrically robust fatigue with use of psychometrically robust short forms and CAT.short forms and CAT.

Fatigue as a vital sign?Fatigue as a vital sign? May be useful to consider fatigue as a May be useful to consider fatigue as a

measurable property -- like temperature, blood measurable property -- like temperature, blood pressure, etc – not a disease- or treatment-pressure, etc – not a disease- or treatment-specific variable.specific variable.

Questions?Questions?

Zeeshan Butt, Ph.D.Zeeshan Butt, Ph.D.Research Scientist, Center on Outcomes, Research, and Education (CORE)Research Scientist, Center on Outcomes, Research, and Education (CORE)Research Assistant Professor, Northwestern University Feinberg School of Research Assistant Professor, Northwestern University Feinberg School of

MedicineMedicine

224-364-7596224-364-7596z-butt@northwestern.eduz-butt@northwestern.edu

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PROMIS Fatigue Short-FormPROMIS Fatigue Short-Form

Garcia et al (2007) Journal of Clinical Oncology

In the past 7 days … Never Rarely Some-times

Often Always

FATEXP 20

How often did you feel tired? 1

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FATEXP 5

How often did you experience extreme exhaustion? 1

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FATEXP 18

How often did you run out of energy? 1

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FATIMP 33

How often did your fatigue limit you at work (include work at home)?

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FATIMP 30

How often were you too tired to think clearly? 1

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FATIMP 21

How often were you too tired to take a bath or shower? 1

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FATIMP 40

How often did you have enough energy to exercise strenuously?

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Reprinted with permission of the PROMIS Health Organization and the PROMIS Cooperative Group © 2007.