Neuro-QOL: Health-Related Quality of Life Measures for

Neurology Research and Practice

Claudia Scala Moy, PhD

Office of Clinical ResearchNational Institute of Neurological Disorders and Stroke

Disclosures

• No financial disclosures• This work represents a collaboration between

NINDS and Northwestern University• Funded by NINDS contract HHSN 2652004236-

01C• Thanks to David Cella, Cindy Nowinski, Richard

Gershon, David Victorson, Vitali Ustsinovich

Neuro-QOL Team

Need for a New Tool in Neurological Disorders

• Many Disorders• Multitude of generic and targeted

measurement instruments – Many not validated for use in clinical trials– Unresponsive to differences that exist across

different conditions or treatments– Limited by floor and ceiling effects

– Respondent burden

– Research cost

– Lack of consensus about best measurement approaches

NINDS Phase III Stroke Trials

Secondary Prevention of Small Subcortical Stroke

No QOL outcome measure

Field Administration of Stroke Therapy – Magnesium

Rankin (1o), Barthel, NIHSS, SIS (2o)

Efficacy of a Family Telephone Intervention for Stroke

Craig Handicap Assessment and Reporting, Satisfaction with Life Scale

Carotid Revascularization Endarterectomy vs Stenting Trial

SF36, Frenchay Activity Index

Treatment for Post Stroke Depression SSQOL

Warfarin-Aspirin Symptomatic Intracranial Disease Study

No QOL outcome measure

Carotid Occlusion Surgery Study Rankin, NIHSS, mBI, SSQOL

Warfarin vs Aspirin in Reduced Cardiac Ejection Fraction

No QOL outcome measure

Albumin in Acute Stroke EuroQOL

Objectives of NINDS Quality of Life Initiative

• Develop psychometrically robust instrument that is accepted by neurology clinical trials community

• Foster inclusion of QOL measures in clinical research

Purpose of contract

• Develop a core set of questions that cut across chronic neurological disorders

• Develop supplemental questions that address additional concerns of specific diseases, subgroups of patients

Neuro-QOL: Special Features

• Target neurological conditions• Adult and pediatric disorders• Inclusion of ethnic minorities • Field tested Spanish-language version• Assessment of acceptability to neurology

research and clinical community• IRT-based approach/CAT• Available in the public domain

Selection of Target Conditions

• Prevalence of the disease/disorder• Magnitude of the disease’s impact on the

individual• The existence of promising current or new

treatments on the horizon• Multiple domains affected• Chronic nature of the disease/possibility of

seeing HRQL change

Target Conditions

• Adult– Epilepsy– Multiple Sclerosis– Parkinson’s

disease– Stroke– ALS

• Pediatric – Epilepsy– Muscular

dystrophies

Neuro-QOL Collaborations

• Spinal cord injury (SCI-QOL) – D. Tulsky

• Traumatic brain injury (TBI-QOL) – D. Tulsky

• Huntington’s Disease (HD-HRQL) – N. Carlozzi

• Poly trauma (VA) - • PTSD (VA) – S. Luther

PHYSICAL

Adult Domain Framework for Item Banks and Scales

Symptoms

Function/Health

Fatigue-B

Sleep Disturbance-B

Lower Extremity Function- Mobility- B

MENTAL

Cognitive Health

Emotional Health

SOCIALAbility to Participate in Social

Roles & Activities-B

Satisfaction with Social Roles & Activities-B

Bowel Function -D

Upper Extremity Function-Fine Motor, ADL-B

Sexual Function-D

Depression-B

Anxiety-B

Stigma-B

Positive Affect & Well-Being-B

Emotional & Beh. Dyscontrol-B

End of Life Concerns-DCommunication-S

Applied Cognition-General Concerns-B

Applied Cognition-Executive Function-B

B=BankS=ScaleD=Developed but not Tested

Urinary/Bladder Function-D

Pediatric Domain Framework for Item Banks and Scales

PHYSICAL

Symptoms

Function/Health

Pain-B

Fatigue-B

Lower Extremity Function Mobility-S

Upper Extremity FunctionFine Motor, ADL-S

MENTAL

Cognitive Health

Emotional HealthDepression-B

Anxiety-B

Stigma-B

Anger-BApplied Cognition-General Concerns-B

B=BankS= ScaleU=Domain Being Identified

SOCIALSocial Relations-Interactions

with Adults-U

Social Relations- Interactions with Peers-B

Adult Banks and ScalesDomain Format

# Items # Items in

Short Form

Anxiety Bank 21 8Depression Bank 24 8Fatigue Bank 19 8Upper Extremity Function - Fine Motor, ADL Bank 20 8Lower Extremity Function – Mobility Bank 19 8Applied Cognition- Executive Function Bank 13 8Applied Cognition- General Concerns Bank 18 8Emotional and Behavioral Dyscontrol Bank 18 8Positive Affect and Well-Being Bank 23 9Sleep Disturbance Bank 8 NAAbility to Participate in Social Roles and Activities

Bank 45 8

Satisfaction with Social Roles and Activities Bank 45 8Stigma Bank 24 8Communication Scale 5 NA

Pediatric Banks and Scales

Domain Format

# of Items

# Items in Short Form

Anxiety Bank 19 8

Depression Bank 17 8

Anger Bank 8 NAFatigue Bank 13 8

Upper Extremity Function - Fine Motor, ADL Scale 20 NA

Lower Extremity Function –Mobility Scale 20 NA

Applied Cognition- General Concerns Bank 14 8

Social Relations - Interaction with Peers Bank 16 8

Social Relations - Interaction with Adults TBD 9 NAStigma Bank 18 8

Pain Bank 10 NA

Lower Extremity Function – Mobility

T-scores

45

50

55

60 running up and down an incline?taking a 20-minute brisk walk, without stopping to rest?getting into and out of a kneeling position?Are you able to jump up and down?walking 45 minutes on an even surface?climbing stairs step over step without a handrail?going up and down three flights of stairs inside, using a handrail?walking on a slippery surface, outdoors?Are you able to get up off the floor from lying on your back without help?Are you able to go for a walk of at least 15 minutes?How difficult is it for you to go for a walk of at least 15 minutes?standing up from a low, soft couch?crossing the road at a 4-lane traffic light with curbs?going up and down a flight of stairs inside, using a handrail?walking in a busy place without losing your balance?Are you able to run errands and shop?sitting down on a low, soft couch?getting into and out of a truck, bus, shuttle van, or sport utility vehicle?Are you able to step up and down curbs?walking on uneven surfaces?opening a window above shoulder height, while standing?walking in a dark room without falling?standing up from an armless straight chair?using an escalator?Are you able to push open a heavy door?Are you able to get out of bed into a chair?moving from lying on your back to sitting on the side of the bed?Are you able to get in and out of a car?sitting down on an armless straight chair?Are you able to get on and off the toilet?moving from sitting at the side of the bed to lying down on your back?

Applied Cognition - Executive Function

T-Scores

35

36

37

38

39

40

41 remembering a list of 4 or 5 errands without writing it down?keeping important personal papers such as bills, insurance documents and tax forms organized?reading a long book (over 100 pages) over a number of days?taking care of complicated tasks like managing a checking account or getting appliances fixed?handling an unfamiliar problem?organizing what you want to say?checking the accuracy of financial documents?

doing calculations in your head while shopping?planning for and completing regularly scheduled weekly tasks?explaining how to do something involving several steps to another person?managing your time to do most of your daily activities?counting the correct amount of money when making purchases?have planning what to do in the day?learning new tasks or instructions?carrying on a conversation with a familiar person in a noisy environment?

planning an activity several days in advance?remembering where things were placed or put away?using a local street map to locate a new store or doctor's office?putting words together to form grammatically correct sentences?remembering to take medications at the appropriate time?planning for and keeping appointments that are not part of your weekly routine?carrying on a conversation with a small group of familiar people?

dialing familiar numbers such as a family member or doctor?reading and following complex instructions?composing a brief note or e-mail to someone?

understanding pictures that explain how to assemble something?looking up a phone number or address in the phone book?making yourself understood to other people during ordinary conversations?

understanding familiar people during ordinary conversations?

Advantages of Short-Forms Developed from Item Banks

• Select a set of items that are matched to the severity level of the target population.

• All scales built from the same item bank are linked on a common metric.

Validation phase

• Multiple disease groups• Ethnic minorities• Geographically diverse populations• Quality of proxy reporting• Evaluation of modes of administration• Approaches to missing data• Longitudinal study issues (response to

change, practice effects, etc.)

Neuro-QOL Testing Highlights

• WAVE Ia: Online clinical testing in adults (n=500) and children (n=100)

• WAVE Ib: Online English and Spanish general population calibration testing for adults (n= 3000) and children (n=1500)

• WAVE II: Clinical validation testing of IRT-calibrated short forms

Clinical Validation of Short Forms

Purpose: to evaluate the reliability, validity and responsiveness of Neuro-QOL short forms and scales in clinical neurology populations– Administered Neuro-QOL Short Forms and

clinical validation measures (both cross-disease and disease-specific), physician ratings and chart review at baseline and at a 180-day follow up (to assess responsiveness).

– Test-retest reliability of the Neuro-QOL Short Forms was evaluated at 7 days.

Neuro-QOL Wave 2 Testing Sites

Chicago sites : *•NMFF •NorthShore University HealthSystem •NU Parkinson’s Disease Center•Rehabilitation Institute of Chicago•University of Chicago•Children’s Memorial Hospital

* University of California at Davis

University of Puerto Rico*

*University of Texas HSC at San Antonio

*Dartmouth-Hitchcock Medical Center

Cleveland Clinic

* *University of Pennsylvania

Clinical Validation Sample

Number completing assessment

Baseline 7-day 180-day

Multiple Sclerosis 161 125 132

Parkinson’s disease 120 116 108

Adult Epilepsy 119 119 109

Stroke 101 95 90

Stroke Proxies 84 78 73

ALS 80 77 59

Pediatric Epilepsy 62 60 56

Pediatric Epilepsy Proxies 62 60 56

Muscular Dystrophy 51 48 48

Muscular Dystrophy Proxies 51 48 48

Total: 891 826 779

Clinical Validation Results

• High internal consistency and reliability• Moderate to high correlations with generic

and disease-specific measures• Responsiveness comparable with legacy

instruments• Neuro-QOL short forms successfully

discriminate between patients grouped by disease severity or other clinical factor.

Overlap between Neuro-QOL, PROMIS and AM-PAC

Domain Neuro-QOL PROMIS AM-PAC

Ability to Participate in Social Roles & Activities X X --

Satisfaction with Social Roles & Activities X X --

Lower Extremity Function - Mobility X X X

Upper Extremity Function – Fine motor, ADL X X X

Depression X X --

Anxiety X X --

Positive Affect and Well-being X X --

Fatigue X X --

Sleep Disturbance X X --

Pain X X --

Stigma X  -- -- 

Applied Cognition – Executive Function X  -- -- 

Applied Cognition – General Concerns X --  X 

Emotional & Behavioral Dyscontrol X  -- -- 

Future of Neuro-QOL

• Create a publicly available, adaptable and sustainable system allowing clinical researchers access to a common item repository and computerized adaptive testing (“CAT”)

Demonstration of Neuro-QOL CATs in:

Upper Extremity Function – Fine Motor, ADL Applied Cognition - Executive Function

Depression

Time 1

Neuro-QOL Physical Function Upper Extremity CAT

Item 1

Item 2

Item 3

Item 4

Final Score after 4 itemsT=25.0 (SE=2.0)

Neuro-QOL Applied Cognition Executive Function CAT

Item 1

Item 2

Item 3

Item 4

Final Score after 4 itemsT=26.0 (SE=2.5)

Neuro-QOL Depression CAT

Item 1

Item 2

Item 3

Item 4

Final Score after 4 itemsT=59.9 (SE=1.8)

Time 1 Scores

120

25

30

35

40

45

50

55

60

65

PFExecDep

Time 1

Time 2

Neuro-QOL Physical Function Upper Extremity CAT

Item 1

Item 2

Item 3

Item 4

Item 5

Item 6

Final Score after 6 itemsT=41.8 (SE=2.6)

Neuro-QOL Applied Cognition Executive Function CAT

Item 1

Item 2

Item 3

Item 4

Item 5

Final Score after 5 itemsT=42.7 (SE=2.6)

Neuro-QOL Depression CAT

Item 1

Item 2

Item 3

Item 4

Final Score after 4 itemsT=51.8 (SE=1.8)

Time 1 and 2 Scores

1 220

25

30

35

40

45

50

55

60

65

PFExecDep

Time 1 Time 2