Health-Related Quality of Life (HRQOL) - 2014

John E. Ware, Jr., PhD

Introduction to the Principles and Practice of Clinical ResearchNational Institutes of Health - Warren G. Magnuson Clinical Center Building 10

Lipsett Amphitheater, Bethesda, MD, December 2, 2013

Professor & Division Chief, Dept. of Quantitative Health Sciences, UMass Medical School Chief Science Officer and Founder, JWRG, Incorporated, Worcester, MA

2

Quality and Outcomes

“The best measure of quality is not how well or how frequently a medical service is given, but how closely the result approaches the fundamental objectives of prolonging life, relieving distress, restoring function, and preventing disability.”

Lembcke, 1952

Lembcke , PA. Measuring the quality of medical care through vital statistics based on hospital service areas: 1. Comparative study of appendectomy rates. Am J Public Health 1952; 42: 276-86.

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Quality of Life (QoL)

•Community•Education

•Family Life•Friendships

•Health•Housing

•Marriage•Nation•Neighborhood•Self•Standard of Living•Work

Source: Campbell, 1981

4

World Health Organization Definition of Health

“Health is a state of complete physical, mental, and social well-being and not merely the absence of disease or infirmity”

WHO, 1948

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Health is Measured in Terms of:

• Bodily structure & function

• Specific symptoms

• What you do/are able to do – functioning

• How you feel – subjective ill- and well-being (+ and -)

• What you say it is – personal evaluation

66666

Clinical Markers

(1)

Specific Symptoms

(2)

Impact of Disease-specific

Problems

(3)

Arthritis SymptomsHave you had the following symptoms: Joint pain, swelling, burning sensation:

• Almost every day• Several days a week• A few days a month• Not at all

(4)

Generic Functioning, Well-being

and Evaluation

X-ray, Disease Progression

Continuum of Disease-specific and Generic Health Measures - Arthritis

Health-related QOL(HRQoL)

GenericHealth

In general, would you say your health is:

• Excellent• Very good• Good• Fair• Poor

How much does your arthritis limit your usual activities or enjoyment of everyday life?

• Not at all• A little• Moderately• Extremely

ArthritisImpact

Adapted from: Wilson and Cleary, JAMA, 1995Ware, Annual Rev. Pub. Health, 1995

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There is More to the Continuum

Clinical Markers

Specific Symptoms

(1) (2) (4)

Generic Functioning, Well-being

and Evaluation

Impact of Disease-specific

Problems

(3)

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Predictive Validity:HRQoL is One of the Best Predictors

Health-Related QOL (HRQoL)

Future healthInpatient expendituresOutpatient expendituresJob lossResponse to treatmentReturn to workWork productivityMortality

(3) (4)

Impact of Disease-specific

Problems

Generic Functioning, Well-being

and Evaluation

9

Summary of Content/Concepts for Widely-Used Generic Health Surveys

Source: Adapted from Ware, 1995

Reported health transition

SIP = Sickness Impact Profile (1976)HIE = Health Insurance Experiment surveys (1979)NHP = Nottingham Health Profile (1980)QLI = Quality of Life Index (1981)COOP = Dartmouth Function Charts (1987)DUKE = Duke Health Profile (1990)MOS FWBP = MOS Functioning & Well-Being Profile

(1992)

MOS SF-36 = MOS 36-Item Short-Form Health Survey (1992)

QWB = Quality of Well-Being Scale (1973)EUROQOL = European Quality of Life Index (1990)HUI = Health Utility Index (1996)SF-6D= SF-36 Utility Index (2002)

PsychometricUtility Concepts and Characteristics SIP HIE NHP QLI COOP DUKE MOS

FWBPMOSSF-36 QWB EQ-5D HUI SF-6D

CONCEPTSPhysical functioning Social functioning Role functioning Psychological distress Health perception (gen’l) Pain Vitality Psychological well-being Sleep Cognitive functioning Quality of life

PROMIS

PROMIS = Patient Reported Outcomes Measurement Information System (2008)

(-)

(-)(-)

(-)

(-)

(-)

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www.nihpromis.orgPROMIS Website

Cella D, Yount S, Rothrock N, et al. PROMIS Cooperative Group. The Patient-Reported Outcomes Measurement Information System (PROMIS): progress of an NIH Roadmap cooperative group during its first two years. Med Care. 2007 May; 45(5 Sup 1):S3-S11.

Cella D, Riley W, Stone A, et al. PROMIS Cooperative Group. The Patient-Reported Outcomes Measurement Information System (PROMIS) developed and tested its first wave of adult self-reported health outcome item banks: 2005-2008. J Clin Epidemiol. 2010 Nov; 63(11):1179-94.

Rose M, Bjorner JB, Becker J, et al. Evaluation of a preliminary physical function item bank supported the expected advantages of the Patient-Reported Outcomes Measurement Information System (PROMIS). J Clin Epidemiol. 2008 Jan; 61(1):17-33.

Varni JW, Thissen D, Stucky BD, et al. PROMIS(®) Parent Proxy Report Scales: an item responsetheory analysis of the parent proxy report item banks. Qual Life Res. 2011 Oct 5.[Epub ahead of print]

PROMIS References

1111

Medical Outcomes Study 36-Item Health Survey (SF-36)

Utility Index(Brazier et al., 2002)

(Lam, Brazier, McGhee 2008)

Physical

Mental

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Generic Health Profiles: Before & After Medication

Best Health

Poorest Health

Component Summaries

SF-36 Subscales

Treatment

Baseline

2530354045505560

2530354045505560

Arthritis

Norm

Physical Mental P M 2530354045505560

30354045505560

Depression

Component Summaries

SF-36 Subscales

Physical Mental P M

Treatment

Baseline

Best Health

Poorest Health

-

Next Step: Integrate and Standardize Disease-specific and Generic Measures

Best Health

Poorest Health

+

2530354045505560

Disease-SpecificImpact Scale

(QDIS)

2530354045505560

Example: Osteoarthritis

Physical HealthGeneric Summary

(PHGS)

US Norms(Mean=50

SD=10)

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Comparison of Content of Generic And Disease-Specific Measures

Health transition (B/S/W)

Health Domains

Physical functioningSocial functioningRole functioningPsychological distressHealth perceptions (general)Pain (bodily)Energy/fatiguePsychological well‐being SleepCognitive functioning

SIP

Quality of life

PROMIS

Sexual functioningSpecific symptomsSpecific treatments

Generic*MOSFWBP

WO‐MAC

Disease‐Specific*

SAQ

KDQOL

StGeorg

DQOL

ML‐HFQ

DQOL ‐ Diabetes Quality of Life  MeasureKDQOL  ‐ Kidney Disease Quality of Life  QuestionnaireMLHFQ  ‐ Minnesota Living with Heart Failure  QuestionnaireSAQ  ‐ Seattle Angina QuestionnaireSt. George's   Respiratory QuestionnaireWOMAC  ‐ Western Ontario and Mac Master's  Arthritis Index

SIP  ‐ Sickness Impact Profile, 136 items (1976)MOS FWBP ‐MOS Functioning and Well‐Being Profile, 

149 items (1992)PROMIS  ‐ Patient Reported Outcomes Measurement

Information  System (2007‐on)

*Source:   Comparison adapted from Ware 1987; Ware, 1995

Content Areas* QOL Disease Impact Scale (QDIS)

1. Global (“activity” and “QOL”)2. Physical Functioning3. Mobility4. General Health 5. Fatigue6. Cognitive7. Emotional8. Sleep9. Role Functioning 10. Social Functioning

*Note: Bank of 49 items reduced to 25 items with attribution to specific condition

GenericAttribution

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During the past 4 weeks, how often did your healthlimit your ability to do your everyday activities?

• Very often • Often • Sometimes• Rarely• Never

Anatomy of a Survey Item:QDIS Changes Attribution from Health

to Specific Disease

health

Disease-Specific Attribution

arthritis

Early Reference: Patrick DL, Deyo RA. Generic and Disease-specific Measures in Assessing Health Status and Quality of Life. Medical Care. 1989;27(3):S217-S232.

QDIS Reference: QOL Disease Impact Scale (QDIS); Ware JE, Guyer R, Harrington M, Boulanger R. Quality of Life Research, 2012.

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• Standardized Metrics

• Adaptive survey administrations

• Norm-based scoring

• Internet and mobile data collection

Better Measures Are Being ConstructedSource:

Business Week

11/26/01

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100

0

20

30

40

50

Mean = 50SD = 10

Climbing several flights of stairs

Walk one hundred yards

Bathing or dressing, Limited a little

NormVigorous Activities, Not limited

Improving the Physical Function “Ruler”

1980 Old “Ruler”

> 75%@ Ceiling

1990 NEW “Ruler”

> 30%@ Ceiling

00.2

0.4

0.6

10 20 30 40 50 60

.76

.24

.01a b

Limiteda little

Limiteda lot0.8

1.0 NotLimited

2008BETTER “Ruler”< 3 % @ Ceiling

20

30

40

50

70

60

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We Need the Health Equivalent of a Two-Sided Tape Measure

52 centimeters = 20.5 inches

and Public-Private Partnerships Meetingthe Needs of Research and Business

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Short-Form Surveysand Ceiling Effects

1

3

1

3

7

1

3

5

Measuring Too Low -CeilingEffect

21Cooking Thermometer

Some Thermometers Focus on a Very Narrow Range

130–190 °F54–88 °C

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Temperature

F° = 98.6 C° = 37.0

Example: Cross-Calibrating Celsius and Fahrenheit

WaterFreezes

NormalHumanBlood

ShirtSleeve

Weather

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CAT

Solution: Adaptive Survey Methods

Patient scores here

CAT = Computerized Adaptive Testing

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Moderate

Adaptive Assessments of Disease ImpactMatch Questions to Each Patient’s Level

10

30

40

70

80

Mild

Severe

50

60

40

20

Higher is worse.Mean = 50SD = 10

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First QuestionNoisy Score Estimate (+/- 15)

10

30

40

70

80

50

60

40

20

Score estimate,1st response = 62+/- 15

Moderate

Mild

Severe

Higher is worse.Mean = 50SD = 10

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Second Question: Standard Error Reduced by One Third

Score estimate,2 responses = 64+/- 10

10

30

40

80

50

40

20

70

60

Moderate

Mild

Severe

Higher is worse.Mean = 50SD = 10

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Third Question: Standard ErrorCut in Half

10

30

40

80

50

40

20

70

60

Moderate

Mild

Severe Score estimate,3 responses = 63+/- 7

Higher is worse.Mean = 50SD = 10

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Fourth Question: Standard ErrorCut by Two Thirds

10

30

40

80

50

40

20

70

60

Moderate

Mild

Severe Score estimate,4 responses = 62+/- 5

Higher is worse.Mean = 50SD = 10

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Practical Implications of CATin Health Assessment

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Reference: Ware JE, Jr., Bjorner JB, Kosinski M: Practical implications of item response theory and computerized adaptive testing: A brief summary of ongoing studies of widely used headache impact scales. Medical Care 2000;38:II73-82.

Static 5-Item Headache Pain Measure

“Ceiling Effect”

r = 0.536N = 1016

Dynamic 5-Item HeadachePain Measure

r = 0.938N = 1016

CriterionScore

CriterionScore

A Promising Solution in 1999: CAT-Based Health Assessment

3 SD units

NoDisability

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Performance of 5-item CAT Scores Confirmed in NIH-Sponsored Studies

r = 0.98N = 2,753

Mental Health Headache Disability

r = 0.94N = 1,016

-2-10123

-2 -1 0 1 2 3

DiabetesImpact

r = 0.93N = 100

20 30 40 50 60 70

Pediatric Disability

r = 0.96N = 263

10

20

30

40

50

60

70

Chronic Kidney Disease

-3

-2

-1

0

1

2

-4-3 -2 -1 0 1 2

r = 0.95N = 1,846

Post AcuteRehabilitation

15

20

25

30

35

40

45

50

20 25 30 35 40 45

r = 0.95N = 485

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What are the Advantages of Dynamic Assessments?

• More accurate risk screening • Reliable enough to monitor individual

outcomes• Brevity of a short form –

90% reduction in respondent burden• Elimination of “ceiling” & “floor” effects • Can be administered using various data

collection technologies• Markedly reduced data collection costs• Monitor data quality in real time

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Matching Methods to Applications

1

2

3

4

5

6

7

1

3

5

7

Single-Item

1

2

3

4

5

Multi-ItemScale

PopulationSurveys

Group-LevelStudies

Patient-LevelAssessments

“Item Bank” (CAT Dynamic)

7

6

Most Functionally Impaired

NoisyIndividual

Classification

Very AccurateIndividual

Classification

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Adaptive Survey Logic (ASLX ®) Flow Chart

ASLX® Screen Estimate Score & CI from Screen

NEG

POS

SupplementalDomain

Assessment(CAT/Static)* 

Repeat Cycle for Each Generic Domain

Repeat Cycle for Each Chronic Condition

ConditionPresent?

PosSupplementalDisease ImpactAssessment

(CAT/Static)*

Follow‐upAssessmentModules

GenericAssessment

Survey ContentAnd User

Interface (UI)

GenericHealth 

Assessments

QDISAssessments(QOLIX® CCC)

YES

ASLX® Screen

NONext Condition

Abbreviations: QOLIX® DIS; Chronic condition checklist QOLIX® CCC), Computer adaptive test (CAT), Confidence interval (CI), Diagnosis (Dx), Electronic data capture (EDC), User interface (UI); Follow-up assessment modules vary across

applications.

Impact  Estimated

From Screening

Neg

353535

• Diagnosis• Disease severity• Responders • Treatments

HR-QOL

GoldStandard

• Work productivity• Costs of care• Mortality• Self- evaluated

health

OtherMeasures& Methods

• Diagnosis• Disease severity• Clinical endpoint• Treatment

• Work productivity• Costs of care• Mortality• Self-evaluated

health

GoldStandard

OtherMeasures& Methods

Adapted from: Ware JE, Jr. and Keller SD: Interpreting general health measures, in: Quality of Life and Pharmacoeconomics in Clinical Trials. Philadelphia, PA: Lippincott-Raven Publishers; 1995: Chapter 47.

Clinical CausesEconomic & Social

Consequences

HRQoL Validation Strategies

363636

Interpreting HRQoL Scores

30 40 50

Chronic Lung

Disease

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Average Well Adult

MOS Physical Component Summary (PCS)(Mean = 50, SD = 10)

DiabetesType II

Congestive Heart

Failure

Asthma

Average Adult

PopulationHealth Surveys

Chronic Disease Registry

General Population Health SurveysChronic Disease Registry

45

ChronicKidneyDisease

35

37373737

Interpreting HRQoL Scores

30 40 50

Chronic Lung

Disease

55

Average Well Adult

MOS Physical Component Summary (PCS)(Mean = 50, SD = 10)

DiabetesType II

Congestive Heart

Failure

Asthma

Average Adult

General Population Health SurveysChronic Disease Registry

45

Clinical Trials

ChronicKidneyDisease

35

RAAfterRx

RABefore

Rx

TreatmentEffect (net)

Strand etal Arth & Rheum, 1999;42(9): 1870-78

PopulationHealth Surveys

ClinicalTrials

Chronic Disease Registry

• Content of questionnaire items

• Statistically significant change

• Important reduction in disease burden

• Reduction in subsequent expenditures

• Substantial increase in work productivity

38383838

Are Generic HRQoL Measures Responsive?

Clinical Markers

Specific Symptoms

Impact of Disease-specific

Problems

Reference: Ware JE and Frendl D “Systematic review of the responsiveness of SF-36 HealthSurvey measures to efficacious pharmaceutical therapies in published double-blind randomized controlled trials.” Presentation at the 13th Annual ISPOR Congress, Prague CzechRepublic, 11/6/2010; Value in Health, Vol 13, (7): A239–A250.

(1) (2) (3) (4)

How much does your arthritis limit your usual activities or enjoyment of everyday life?

• Not at all• A little• Moderately• Extremely

ArthritisImpact

In general, would you say your health is:

• Excellent• Very good• Good• Fair• Poor

GenericHealth

Arthritis SymptomsHave you had the following symptoms: Joint pain, swelling, burning sensation:

• Almost every day• Several days a week• A few days a month• Not at all

SF-36 RCTs

Generic Functioning, Well-being

and Evaluation

X-ray, Disease Progression

SF-36 agreed with primary endpoint (across Rx):

• 219 of 253 RCTs• 86.6%

393939

Reference – Headache Impact: MS Bayliss, JE Dewey, R Cady etal., A.Study of the Feasibility of Internet Administration of a computerizedhealth survey: The Headache Impact Test (HIT), Quality of Life Research, 2003, 12: 953-961

References – Asthma Control: Nathan RA, Sorkness CA, Kosinski M et al., “Development of the Asthma Control Test: A survey for assessing asthma control. Journal of Allergy and Clinical Immunology. 2004;113: 59-65.

Internet Sampling and Data Collection

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Health Outcomes Research Using Handhelds – Mobile Metrics

Ware NIH – Health-Related Quality of Life - 2014 40

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Final Comment

For more information: john.ware@umassmed.edu

Business Week 11/26/2001