ANEMIA AND HEALTH-RELATED QUALITY OF LIFE MEASURES: PSYCHOMETRIC CHARACTERISTICS OF INSTRUMENTS

Dennis A. Revicki, PhDMiriam Kimel, PhD

Center for Health Outcomes Research, United BioSource Corporation, Bethesda, Maryland, USA

Prepared for the KDIGO Controversies Conference: Coordination of Clinical Practice Guidelines for Anemia in CKD, New York, NY, October 15, 2007

OVERVIEWOVERVIEW

Why ask patients about their health status?Why ask patients about their health status?

Development and psychometric evaluation of health status Development and psychometric evaluation of health status measuresmeasures

Summary of psychometric qualities of frequently used HRQL Summary of psychometric qualities of frequently used HRQL measuresmeasures

– Content coverageContent coverage

– Measurement qualitiesMeasurement qualities

Future of HRQL measurementFuture of HRQL measurement

– NIH PROMIS initiativeNIH PROMIS initiative

WHY ASK PATIENTS ABOUT THEIR WHY ASK PATIENTS ABOUT THEIR HEALTH STATUS?HEALTH STATUS?

HRQL data describe the impact of treatment and disease on HRQL data describe the impact of treatment and disease on symptoms, functioning and well-being.symptoms, functioning and well-being.

Patients provide a unique perspective on the impact of Patients provide a unique perspective on the impact of disease and treatment on their functioning and well-beingdisease and treatment on their functioning and well-being

Physiologic, laboratory and clinician evaluations are Physiologic, laboratory and clinician evaluations are associated with but not identical to HRQL measuresassociated with but not identical to HRQL measures

HRQL measures extend and translate clinical endpointsHRQL measures extend and translate clinical endpoints

KEY CONCEPTS AND ASSUMPTIONSKEY CONCEPTS AND ASSUMPTIONS

Patient’s experience provides a unique and valuable Patient’s experience provides a unique and valuable contribution to understanding treatment effectivenesscontribution to understanding treatment effectiveness

Information provided by patient is inherently subjectiveInformation provided by patient is inherently subjective

Scientific methods for measuring subjective outcomes are Scientific methods for measuring subjective outcomes are well-developed and are foundation of HRQL assessmentwell-developed and are foundation of HRQL assessment

Need scientifically adequate clinical trial designs and Need scientifically adequate clinical trial designs and statistical analysesstatistical analyses

“Objective” “Subjective”Exercise test versus physical functioning, r = 0.40

HRQL VERSUS EFFICACY AND SAFETYHRQL VERSUS EFFICACY AND SAFETY

HRQL is the ultimate outcome of health care interventions HRQL is the ultimate outcome of health care interventions (implies survival)(implies survival)

No single outcome adequately represents results of treatmentNo single outcome adequately represents results of treatment

HRQL assesses integrated effects of treatmentHRQL assesses integrated effects of treatment

HRQL AND CHRONIC KIDNEY DISEASEHRQL AND CHRONIC KIDNEY DISEASE

CKD is associated with broad and meaningful impairment to CKD is associated with broad and meaningful impairment to HRQL outcomes HRQL outcomes

HRQL measures predict mortality in CKD patients, even after HRQL measures predict mortality in CKD patients, even after adjustment for demographic and clinical variablesadjustment for demographic and clinical variables

Treatments for anemia have demonstrated impact on Treatments for anemia have demonstrated impact on symptoms and functioningsymptoms and functioning

HEALTH STATUS IMPAIRED IN CKD HEALTH STATUS IMPAIRED IN CKD PATIENTSPATIENTS

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90

PF PR PN GH VT SF ER MH

Singh (2006)

Normative SF-36

Perlman (2005) CKD

COMPARISON OF MEAN QOL SCORES FOR COMPARISON OF MEAN QOL SCORES FOR PATIENTS WITH CKD, END-STAGE RENAL PATIENTS WITH CKD, END-STAGE RENAL DISEASE, AND THE GENERAL POPULATIONDISEASE, AND THE GENERAL POPULATION

Source: Perlman et al. 2005

SURVIVAL PROPORTIONAL HAZARDS SURVIVAL PROPORTIONAL HAZARDS MODEL*MODEL*

CovariateCovariateSign of Sign of

CoefficientCoefficientUnit of Unit of

AnalysisAnalysis

Percent Percent Survival Survival

Change Per Change Per Unit Unit

ChangeChange††

95% Confidence 95% Confidence Interval for Percent Interval for Percent

Survival Change Per Survival Change Per UnitUnit

PP ValueValue‡‡

AlbuminAlbumin -- 0.1 g/dL0.1 g/dL +10.0+10.0 6.2 to 146.2 to 14 <0.0001<0.0001

AgeAge ++ 1 yr1 yr -2.8-2.8 1.4 to 4.11.4 to 4.1 0.00020.0002

nPCRnPCR -- 0.1 g/kg/d0.1 g/kg/d +17.2+17.2 5.4 to 275.4 to 27 0.00530.0053

PCSPCS -- 5 points5 points +10.4+10.4 1.1 to 181.1 to 18 0.02260.0226

Kt/VKt/V -- 0.1 Kt/V0.1 Kt/V +10.8+10.8 0.6 to 190.6 to 19 0.03730.0373

Is diabeticIs diabetic ++ 0.17390.1739

Is not whiteIs not white -- 0.17730.1773

Is maleIs male ++ 0.44920.4492

MCSMCS -- 5 points5 points +1.4+1.4 -6.5 to 8.9-6.5 to 8.9 0.72800.7280

* For the model, P < 0.0001 (Wald)† The percent change in the probability of survival per unit change of the covariate.‡ Chi-squared.

Source: DeOreo et al. 1997

CORRELATIONS BETWEEN CHANGES IN CORRELATIONS BETWEEN CHANGES IN HCT AND HRQL SCORESHCT AND HRQL SCORES

Source: Revicki et al. 1995

CHANGES IN HCTCHANGES IN HCT

ScoreScore Week 16Week 16 Week 48Week 48

EnergyEnergy 0.35*0.35* 0.37*0.37*

Physical functionPhysical function 0.37*0.37* 0.35*0.35*

* P < 0.05* P < 0.05

A. Identify Concepts & Develop Conceptual Framework

Identify concepts and domains.Identify intended application and population

Hypothesize expected relationships among concepts

D. Modify InstrumentRevise measurement conceptChange applicationChange mode of administrationAdapt for culture or languageOther modifications

B. Create InstrumentGenerate items

Choose data collection method

Choose recall periodChoose response options

Evaluate patient understanding

Develop instructionsIdentify scoring

Format instrumentAssess burden

Confirm conceptual frameworkFinalize items & instrument

C. Assess Measurement PropertiesEvaluate reliability, validity, and ability to detect change

Propose methods for interpretation

PRO

MEASUREMENT ATTRIBUTES AND REVIEW MEASUREMENT ATTRIBUTES AND REVIEW CRITERIA FOR HRQL INSTRUMENTSCRITERIA FOR HRQL INSTRUMENTS

Attribute Criteria

1. Conceptual and measurement model Content validity and framework for concept to be measured

Conceptual and empirical basis for item content and subscales

2. Reliability Internal consistency (homogeneity)

Reproducibility (test-retest reliability)

Inter-rater reliability

3. Validity Degree to which the instrument measures what it intends to measure.

Construct-related

Criterion-relayed

MEASUREMENT ATTRIBUTES AND REVIEW MEASUREMENT ATTRIBUTES AND REVIEW CRITERIA FOR HRQL INSTRUMENTS CRITERIA FOR HRQL INSTRUMENTS (CONTINUED)(CONTINUED)

4. Responsiveness An instrument’s ability to detect change over time

5. Interpretability Degree to which one can assign easily understood meaning to an instrument’s quantitative scores.

RESPONSIVENESS AND MIDRESPONSIVENESS AND MID

Recommended approach, and evolving consensus: Estimate the MID based on several anchor-based

methods, with relevant clinical or patient-based indicators.

Examine various distribution-based estimates (i.e., effect size, standardized response mean, etc.) as supportive information.

Triangulate on a single value or small range of values for the MID.

Confidence in a specific MID value evolves over time and is confirmed by additional research evidence, including clinical trial experience.

Source: Revicki et al. (in press)

HRQL MEASURES USED IN CKD HRQL MEASURES USED IN CKD

Kidney Disease QuestionnaireKidney Disease Questionnaire– Physical symptoms, fatigue, relationships, depression, frustrationPhysical symptoms, fatigue, relationships, depression, frustration

SF-36 Health Survey SF-36 Health Survey – Physical function, pain, vitality, role-physical, role-emotional, Physical function, pain, vitality, role-physical, role-emotional,

social function, general health, mental healthsocial function, general health, mental health

Kidney Disease Quality of Life QuestionnaireKidney Disease Quality of Life Questionnaire– Includes SF-36Includes SF-36

– Kidney disease-specific domainsKidney disease-specific domains

Properties of HRQL Measures in Anemia in Properties of HRQL Measures in Anemia in CKDCKD

Conceptual and Measurement Model KDQ SF-36 KDQOL-SF

Concept to be measured described ++++ ++++ ++++

Content validity based on literature review 0 ++ ++

Content validity based on focus groups or cognitive debriefing interviews with patients with chronic renal disease and anemia

++ ++ ++

Content validity based on clinician or expert review ++ ++ ++

Specific conceptual framework which identifies concept and unique items (e.g., exploratory factor analysis or via literature)

++ ++ ++

Evidence of scale variability (i.e., item and scale distributions, frequencies)

0 ++ ++

Intended level of measurement (e.g., ordinal, interval, ratio) ++

++ ++

Record of item development (i.e., rational for item retention and deletion)

++ ++ ++

Rationale for recall period 0 0 0

Reliability

Internal consistency reliability + ++ ++

Reproducibility ++ + +

Properties of HRQL Measures in Anemia in Properties of HRQL Measures in Anemia in CKDCKD (continued)(continued)

Conceptual and Measurement Model KDQ SF-36 KDQOL-SF

Validity

Content-related (see above) ++ ++ ++

Construct-related ++++ ++++ ++++

Criterion-related 0 + 0

Responsiveness

Anchor-based + + +

Distribution-based methods (i.e., effect size, SEM) + + +

Interpretability

MID estimates 0 0 0

Responder analysis 0 0 0

Respondent Burden

Time needed to complete 0 ++ ++

Reading and comprehension levels 0 0 0

Special requirements 0 0 0

Degree of missing data 0 0 0

Properties of HRQL Measures in Anemia in Properties of HRQL Measures in Anemia in CKDCKD (continued)(continued)

Conceptual and Measurement Model KDQ SF-36 KDQOL-SF

Alternate modes of administration

Self-report ++ ++ ++

Interviewer-administered 0 ++ 0

Cultural and language adaptations or translations

# of available countries with cultural and linguistic translations

? 22 22

# of available translations with evaluations of measurement properties

? 6 6

RESULTS OF CESG ITT ANALYSES: RESULTS OF CESG ITT ANALYSES: TREATMENT VERSUS PLACEBO OVER TIMETREATMENT VERSUS PLACEBO OVER TIME

* Statistically significant after application of Bonferroni adjustment

MEASUREMEASURE Mixed Model p-valueMixed Model p-value LOCF p-valueLOCF p-value

Exercise CapacityExercise Capacity

Treadmill Stress Test Treadmill Stress Test 0.0001*0.0001* 0.0001*0.0001*

6-Minute Walk6-Minute Walk 0.04980.0498 0.05080.0508

Physical Function Physical Function

SIP Physical SummarySIP Physical Summary 0.0015*0.0015* 0.0004*0.0004*

Ambulation Ambulation 0.00770.0077 0.01270.0127

Body Care & Movement Body Care & Movement 0.00680.0068 0.0016*0.0016*

SIP Home Management SIP Home Management 0.02910.0291 0.03870.0387

SymptomsSymptoms

KDQ Fatigue KDQ Fatigue 0.0001*0.0001* 0.0001*0.0001*

KDQ Energy SymptomKDQ Energy Symptom 0.01180.0118 0.03140.0314

KDQ Weakness SymptomKDQ Weakness Symptom 0.01100.0110 0.01870.0187

KDQ Physical SymptomsKDQ Physical Symptoms 0.0001*0.0001* 0.0001*0.0001*

KDQ Shortness of Breath SymptomKDQ Shortness of Breath Symptom 0.79690.7969 0.79610.7961

6 Month Change

SIP Physical Summary

KDQ Fatigue

SIP Home Management

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Group B

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KDQ Physical Symptoms

Minutes walked

Distance Walked

CHANGES IN HRQL SCORES IN HIGH AND CHANGES IN HRQL SCORES IN HIGH AND LOW HGB GROUPLOW HGB GROUP

Source: Drueke et al 2006

*Threshold indicates established clinically meaningful difference as defined in literature, or minimally important effect size of ½ SD baseline value

PHYSICAL FUNCTION SUPPORTING PHYSICAL FUNCTION SUPPORTING EVIDENCEEVIDENCE

MEASUREMEASURE STUDYSTUDY DESIGNDESIGN THRESHOLD*THRESHOLD* CHANGECHANGE P-valueP-value

Physician-assessed Physician-assessed KarnofskyKarnofsky Evans (19900Evans (19900 Single-armSingle-arm 1010 5.05.0 <0.001<0.001

Delano (1989)Delano (1989) Single-armSingle-arm 1010 10.610.6 Not evaluatedNot evaluated

Harris (1991)Harris (1991) Single-armSingle-arm 1010 12.012.0 <0.0001<0.0001

Patient-reported Patient-reported KarnofskyKarnofsky Moreno (1996)Moreno (1996) ControlledControlled 1010 12.612.6 <0.0001<0.0001

Moreno (2000)Moreno (2000) Single-armSingle-arm 1010 2.82.8 <0.01<0.01

SIP Physical FunctionSIP Physical Function McMahon (1992)McMahon (1992) Cross-overCross-over 5.15.1 7.47.4 <0.01<0.01

Moreno (1996)Moreno (1996) ControlledControlled 6.86.8 5.85.8 <0.0001<0.0001

McMahon (2000)McMahon (2000) Cross-overCross-over 3.03.0 2.72.7 <0.01<0.01

KDQ Physical SymptomsKDQ Physical Symptoms Muirhead (1992)Muirhead (1992) RCTRCT 0.50.5 0.90.9 <0.005<0.005

Foley (2000)Foley (2000) RCTRCT 0.50.5 1.11.1 Not evaluatedNot evaluated

Furuland (2003)Furuland (2003) RCTRCT 0.50.5 0.70.7 <0.05<0.05

SF-36 Physical SF-36 Physical FunctioningFunctioning Beusterien (1996)Beusterien (1996) ControlledControlled 88 3.73.7 <0.05<0.05

Besarab (1998)Besarab (1998) RCTRCT 88 Not evaluableNot evaluable <0.05<0.05

Other: “Physical Activity”Other: “Physical Activity” Barany (1990)Barany (1990) Single-armSingle-arm 11 11 <0.05<0.05

Other: “Physical Activity”Other: “Physical Activity” Barany (1993)Barany (1993) ControlledControlled 0.040.04 0.060.06 <0.01<0.01

Clinically Meaningful or Statistically significant Not Clinically Meaningful or Statistically significant

*Threshold indicates established clinically meaningful difference as defined in literature, or minimally important effect size of ½ SD baseline value

ENERGY SUPPORTING EVIDENCEENERGY SUPPORTING EVIDENCE

MEASUREMEASURE STUDYSTUDY DESIGNDESIGN THRESHOLD*THRESHOLD* CHANGECHANGE P-valueP-value

KDQ FatigueKDQ Fatigue Muirhead (1992)Muirhead (1992) RCTRCT 0.70.7 0.80.8 <0.05<0.05

Foley (2000)Foley (2000) RCTRCT 0.710.71 0.040.04 <0.01<0.01

Fatigue SymptomsFatigue Symptoms Evans (1990)Evans (1990) Single-armSingle-arm 0.190.19 0.260.26 <0.001<0.001

Harris (1991)Harris (1991) Single-armSingle-arm 0.870.87 1.661.66 <0.0001<0.0001

NHP: EnergyNHP: Energy Evans (1990)Evans (1990) Single-armSingle-arm Not evaluableNot evaluable 2727 <0.001<0.001

NHP: Energy (%)NHP: Energy (%) Auer (1990)Auer (1990) Single-armSingle-arm 0.240.24 0.50.5 <0.0005<0.0005

Auer (1992)Auer (1992) Single-armSingle-arm 0.220.22 0.520.52 <0.0001<0.0001

Clinically Meaningful or statistically significant Not clinically meaningful or statistically significant

† = Cycle ergometer tests vary in cycle speed, inclination, and termination ; ‡ = meters walked, * = L/min

EXERCISE CAPACITY SUPPORTING EXERCISE CAPACITY SUPPORTING EVIDENCEEVIDENCE

STUDY STUDY PROTOCOLPROTOCOL BASELINEBASELINE POSTPOST CHANGECHANGE P-valueP-value

VOVO2 2 (ml/kg/min)(ml/kg/min)

Mayer (1988)Mayer (1988) Cycle Ergometer TestCycle Ergometer Test†† 16.016.0 23.223.2 7.27.2 <0.02<0.02

Baraldi (1990)Baraldi (1990) Cycle Ergometer TestCycle Ergometer Test†† 24.124.1 32.632.6 8.58.5 <0.05<0.05

Grunze (1990)*Grunze (1990)* Cycle Ergometer TestCycle Ergometer Test†† 1.191.19 1.371.37 0.180.18 <0.05<0.05

Robertson (1990)Robertson (1990) Cycle Ergometer TestCycle Ergometer Test†† 15.315.3 17.817.8 2.52.5 <0.0005<0.0005

Lundin (1991)Lundin (1991) Cycle Ergometer TestCycle Ergometer Test†† 15.115.1 22.722.7 7.67.6 <0.003<0.003

Metra (1991)Metra (1991) Cycle Ergometer TestCycle Ergometer Test†† 21.421.4 26.626.6 5.25.2 <0.001<0.001

Lewis (1993)Lewis (1993) Weber Treadmill ProtocolWeber Treadmill Protocol 18.718.7 25.125.1 6.46.4 <0.05<0.05

Marrades (1996)Marrades (1996) Cycle Ergometer TestCycle Ergometer Test†† 25.425.4 33.133.1 7.77.7 0.0030.003

Treadmill Test (minutes walked)Treadmill Test (minutes walked)

Robertson (1990)Robertson (1990) Cycle Ergometer TestCycle Ergometer Test†† 6.456.45 7.607.60 1.151.15 <0.0005<0.0005

Lundin (1991)Lundin (1991) Maximal Treadmill TestMaximal Treadmill Test 6.06.0 9.19.1 3.13.1 <0.001<0.001

Hase (1993)Hase (1993) Bruce Treadmill Protocol Bruce Treadmill Protocol 4.634.63 6.406.40 1.771.77 <0.01<0.01

Lewis (1993)Lewis (1993) Weber Treadmill ProtocolWeber Treadmill Protocol 15.215.2 21.421.4 6.26.2 <0.05<0.05

Metra (1991)Metra (1991) Cycle Ergometer TestCycle Ergometer Test†† 9.629.62 11.911.9 2.322.32 <0.05<0.05

6-minute walk6-minute walk

Harris (1991)Harris (1991) 6 Minute Walk Test6 Minute Walk Test‡‡ 400400 600600 200200 <0.001<0.001

Statistically significant

FUTURE OF PRO MEASUREMENT: FUTURE OF PRO MEASUREMENT: NIH PROMISNIH PROMIS

Improve assessment of self- reported symptoms and Improve assessment of self- reported symptoms and domains of HRQL for application across a wide range of domains of HRQL for application across a wide range of chronic diseaseschronic diseases

Develop and test a large bank of items for measuring PROsDevelop and test a large bank of items for measuring PROs

Develop computer-adaptive testing (CAT) for efficient Develop computer-adaptive testing (CAT) for efficient assessment of PROsassessment of PROs

Create a publicly available, flexible, and sustainable system Create a publicly available, flexible, and sustainable system allowing researchers to access to item banks and CAT toolsallowing researchers to access to item banks and CAT tools

PROMIS DOMAIN HIERARCHYPROMIS DOMAIN HIERARCHY

Negative Impacts of illness

Anxiety

Anger/Aggression

Depression

Substance Abuse

Performance

Satisfaction

Physical Health

Satisfaction

Mental Health

Satisfaction

Social Health

Satisfaction

Self-reported Health

Satisfaction

Other

Cognitive Function

Emotional Distress

Role Participation

Social Support

•Self Concept•Stress Response•Spirituality/Meaning•Social Impact

Positive Impacts of Illness

Subjective Well-Being (positive affect)

Meaning and Coherence (spirituality)

Mastery and Control (self-efficacy)

Positive Psychological Functioning

Pain

Fatigue

Sleep/Wake Function**

Sexual Function

Symptoms

Upper Extremities: grip, buttons, etc (dexterity)

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

Activities: IADL (e.g. errands)

Lower Extremities: walking, arising, etc (mobility)Function/Disability

ItemRespons

eTheory(IRT)

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

0.0

0.5

1.0

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-3 -2 -1 0 1 2 3

Theta

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Short FormInstruments

CAT

Items fromInstrument

A

Item Pool

Items fromInstrument

B

Items fromInstrument

C

NewItems

Questionnaireadministered to largerepresentative sample

SecondaryData Analysis

CognitiveTesting

FocusGroups

Content ExpertReview

ITEM BANKSITEM BANKS

no pain

mild pain

moderate pain

severe pain

extreme pain

Pain Item Bank

Item1

Item2

Item3

Item4

Item5

Item6

Item7

Item8

Item9

Itemn

These items are reviewed by experts, patients, and methodologists to make sure:• Item phrasing is clear and understandable for those with low literacy• Item content is related to pain assessment and appropriate for target population• Item adds precision for measuring different levels of pain

An item bank is a large collection of items measuring a single domain, e.g., pain…

ITEM RESPONSE THEORY MODELSITEM RESPONSE THEORY MODELS

IRT models enable reliable and precise measurement of IRT models enable reliable and precise measurement of PROsPROs

– Fewer items needed for equal precisionFewer items needed for equal precision

– Makes assessment brieferMakes 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

– Allowing practical individual assessmentAllowing practical individual assessment

RANGE OF MEASUREMENT

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sit on the edge

of the bed

climb up several stairs

heavy work around the house

strenuous activities

usual physical activities

5 = Not at all5 = Not at all4 = Very little4 = Very little3 = Somewhat3 = Somewhat2 = Quite a lot2 = Quite a lot1 = Cannot do1 = Cannot do

5 = Without any difficulty5 = Without any difficulty4 = With a little difficulty4 = With a little difficulty3 = With some difficulty3 = With some difficulty2 = With much difficulty2 = With much difficulty1 = Unable to do1 = Unable to do

Are you able to …Does your health now limit you in ...

Disability

Physical Function

0.0

Ceiling effect

0.0

Ceiling effect

People with more fatigue

Items less likely to be endorsed

Items more likely to be endorsed

People with less fatigue

PEOPLE AND ITEMS DISTRIBUTED ON PEOPLE AND ITEMS DISTRIBUTED ON THE SAME METRIC: FATIGUETHE SAME METRIC: FATIGUE

THE ADVANTAGES OF CAT-BASED THE ADVANTAGES OF CAT-BASED ASSESSMENTASSESSMENT

Provide an accurate estimate of a person’s score with the Provide an accurate estimate of a person’s score with the minimal number of questionsminimal number of questions

– Questions are selected to match the health status of the Questions are selected to match the health status of the respondentrespondent

CAT minimizes floor and ceiling effectsCAT minimizes floor and ceiling effects

– People near the lower or upper extremes of a scale will receive People near the lower or upper extremes of a scale will receive items that are designed to assess their health statusitems that are designed to assess their health status

SUMMARY SUMMARY

Good availability of HRQL instruments for assessing Good availability of HRQL instruments for assessing outcomes in CKD patients with anemiaoutcomes in CKD patients with anemia

– Evaluating treatment effectsEvaluating treatment effects

– Monitoring health statusMonitoring health status

Good content coverage and psychometrically soundGood content coverage and psychometrically sound

– ReliabilityReliability

– ValidityValidity

– ResponsivenessResponsiveness

Future research needs to focus more on interpretation and Future research needs to focus more on interpretation and clinical significanceclinical significance

PROMIS may provide relevant and psychometrically sound PROMIS may provide relevant and psychometrically sound measures of pain, fatigue, physical functioning and other measures of pain, fatigue, physical functioning and other domainsdomains

CONCLUSIONCONCLUSION

Relevancy of HRQL data for regulatory and clinical decision Relevancy of HRQL data for regulatory and clinical decision making depends on the strength of the research evidence on making depends on the strength of the research evidence on added valueadded value

Safety and clinical efficacy data are insufficient for the Safety and clinical efficacy data are insufficient for the comprehensive understanding of medical treatmentscomprehensive understanding of medical treatments

HRQL is the ultimate outcome of health care interventions and HRQL is the ultimate outcome of health care interventions and is the key to assessing effectiveness beyond safety and is the key to assessing effectiveness beyond safety and efficacyefficacy

Patients, clinicians and regulatory agencies need HRQL data Patients, clinicians and regulatory agencies need HRQL data to make decisions about the benefit and risk of new therapiesto make decisions about the benefit and risk of new therapies

THE GOAL OF MEDICINE (C 1400)THE GOAL OF MEDICINE (C 1400)

““To cure sometimes, to relieve To cure sometimes, to relieve often, to comfort always”often, to comfort always”