assessing patient-reported outcomes

Assessing Patient-Reported Outcomes:

Health related Quality of Life (HRQOL)

Juhee Cho, Ph.D

Department of Health Science & Technology, SAIHST

Sungkyunkwan University

What are Patient-Reported Outcomes (PROs)?

• A patient-reported outcome is the measurement of any aspect of a patient’s health status that comes directly from the patient (i.e., without the interpretation of the patient’s responses by a physician or anyone else).

Patient Outcomes Assessment

Why PROs are Important?• Unique perspective on treatment

effectiveness.• Physiological assessments often do not reflect

how a patient functions or feels (e.g., FEV1)

• May be more reliable than informal interview

• Some treatment effects are known only to the patient

• patient’s symptoms (e.g., fatigue, depression)• how well the patient feels• how well the patient functions• how the patient perceives care/treatment

Question

• PROs and HRQoL is of diminishing importance in the era of emerging targeted therapies?

– True?

– False?

Why?

• Cancer often an incurable illness

• Improvement in patient’s HRQoL is an expectation of appropriate therapy

• Palliation is often the goal

• HRQoL is the product of Patient Reported Outcomes

PROs are Important Endpoints

• PROs are used in clinical trials to

– Describe patients & disease severity

– Trial eligibility

– Treatment effects

– Converge with other outcomes

– Risk/Benefit Evaluation

PRO Domain Hierarchy

Mental Health

Physical Health Symptoms

Pain

Other

Social Health

Role Participation

Social Support

Fatigue

Positive Psychological Functioning

Cognitive Function

Anxiety

Anger/Aggression

Depression

Alcohol & Substance Use

Negative Impacts of illness

Emotional Distress

Subjective Well-Being (positive effect)

Positive Impacts of Illness

Meaning and Coherence (spirituality)

Mastery and Control (self-efficacy)

Performance

Satisfaction

HealthPRO

Satisfaction

Satisfaction

Satisfaction

Function/Disability

Upper Extremities (ADL): walking, arising, etc.

Central (ADL): neck & back (twisting, bending)

Activities: IADL (e.g. errands)

Lower Extremities (ADL): grip, buttons, etc

1. What is HRQOL?

2. What Should You Measure?

3. How Should You Measure it?

4. How is it incorporated into clinical research

Health-Related Quality of Life (HRQOL) Assessment

Health Related Quality of Life (HRQoL)

• Includes a number of domains– Physical functioning: ranges from normal

to complete impairment

– Psychological well-being (depression, anxiety, fear of recurrence)

– Social functioning

HRQoL Dimensions

Physical Functioning Spirituality

Occupational/Role Functioning Future Orientation

Social Functioning Sexuality/Intimacy

Emotional Well-being Health Concerns

Symptom Status Family Well-Being

Financial Concerns Satisfaction w/Care

Global/Overall Perception of Quality of Life

P. Ganz, personal communicationt

HRQOL

FunctionalStatus

GlobalRatings

Symptoms

Quality of Life

What Should You Measure?

HRQOL Assessment

Definitions

• Instrument = Questionnaire

• “Item” = Question

• “Domain” = Dimension= Area of Behavior or Experience

• “Cross-Sectional Design”Compares 2 or More Populations at One Point in Time

• “Longitudinal Design”Assesses Changes in HRQOL Over Time in 1 or More Populations

Types of QOL Instruments

• Health profiles-descriptive questionnaires-measures by a simple metric different aspects of HRQoL across multiple domains

• Generic, multi-dimensional

• Disease-specific, multi-dimensional

• Condition-specific, multi-dimensional

HRQOLHRQOL

SymptomsFunctional

Status

GlobalRatings

uMeasure of Functioning

Focus May be Genericor Disease-Specific

Functional Status

Domain Specific

Linear Analog Self-AssessmentPlace an “X” at a point on the line that best represents how you have felt over the past two weeks.

Your Mood

Happy MiserableX

Simple Average

Sum or Mean of Item or Subscale Scores to Yield a Global Score

This Approach Weights each Item Proportional to its Variance in the

Population Under Study

Example: Quality of Life Index

Aggregated Scores

Symptoms

•Focus:

– Disease (e.g., asthma, CHF, cancer, lung cancer)

– Type of symptom (e.g., pain)

•Dimension(s):

– Frequency

– Severity

– Distress

– Interference with activities

Single Assessment of Overall Health or HRQOL

Global Ratings

Example: E-V-G-F-PHow would you describe your overall state of health [CHECK ONE]?

Excellent

Very Good

Good

Fair

Poor

Why Should You Measure It?

HRQOL Assessment

Operational Definition

HRQOL Assessment Adds Value IF HRQOL Data Can Influence

Overall Conclusions of the Study

HRQOL: Value Added

Nature of the Value Added Depends on Overall Study Goals

• evaluating the effectiveness of interventions

• characterizing treatment-specific outcomes for use in shared decision making

• characterizing the burden of illness

• predicting patient outcomes

• quality-adjusting survival for resource allocation and other policy decisions

Study Goals

Question

HRQoL is relevant to which type(s) of clinical trials:

a. Phase I

b. Phase Ib/II

c. Randomized phase II trial

d. Prospective randomized trial

e. All of the above

Depends On

1. Phase of the Trial

2. Natural History of Disease

Evaluating Effectiveness

Type of Clinical Trial and PRO

• Phase I: not critical-goal is primarily to define MTD or optimal biologic dose

• Phase II: can be used but not essential

– An opportunity to collect pilot data for use in phase III trial

• Phase III-HRQOL data is essential in this

context

Tailoring study design to thenatural history of the disease

3 paradigms:

– Chronic and/or recurrent, non-lethal diseases

– Lethal but curable diseases

– Lethal, incurable diseases

Information Patients Need

Nature of Alternative TreatmentsLikely Outcomes from Treatments

Descriptive Information forEach of the Possible Outcomes

simple, transparent measures

Supporting SharedDecision Making

Characterizing theBurden of Illness

To “Benchmark” Study Populationgeneric health status measures

To Identify Patient Needsdomain-specific measures

symptom-specific measures

Predicting Outcomes

Baseline HRQoL has been Shown to be an independent Predictor for

survival & response to therapy

Breast Cancer

Lung Cancer

functional status & resource use (chronic illness)

How Should You Measure It?

Identify the Respondent

patientsurrogate

provider (MD, RN, other)

HRQoL Assessment

How Should You Measure It?

Choose the Domains to be Measured

disease or domain-specific instrumentgeneric instrument

global assessment of QoL

uIdentify the Respondent

HRQoL Assessment

How Should You Measure It?

Consider the Need for Interpretability

health state descriptionstranslating numeric into clinical differences

uIdentify the RespondentuChoose the Domains to be Measured

HRQoL Assessment

How Should You Measure It?

Choose a Mode of Administration

in person, by phone, mailedcomputer assisted (in person or phone)

self-administered (forms, computer)

uIdentify the RespondentuChoose the Domains to be MeasureduConsider Need for Interpretability

HRQoL Assessment

HRQoL Instruments

• Multi-dimensional HRQoL instruments are available that cover the basic HRQoL domains

– Generic

– Cancer-specific

– Domain-specific

HRQoL Instruments

• Generic types

– Intended for use across broad chronic disease populations

• Allow comparisons across these groups

• Disadvantage: may not permit adequate cancer-specific focus

– Disease caused symptoms

– Treated related symptoms

도 HADS POMS SF-36 QL index SIP NHP ferrans래

.우울사

신치료

상태, 변

다 한 Health outcome 사 .

만 질 health outcome

다 한 Health outcome 사 .

반건강 사

반QoL 사

항수

14 항 65 항 36 항 5 항 136 항 45 항 64 항

상시간

2-3 − 건강한사람: 3-5, 5-7

− : 20

5-10 1 20-30 5-15 8-10

수 0~3(수 우울,

)

0~4(수심리 )

0~100지가능

하 , 수다.

3 point categorical scaling.

수가낮수낮 편.

한버

Validation Validation Validation Validation

비고 짧 시간에숙달 술없 도하게검사가능.

도 고, 다 어에피험가 답에어 움 느낀다는단 .

가 범하게쓰 는도 .하지만말들에게는

쓸수없다.

사 간편하다.건강한사람에게는쓸수없다.

다차원특 지니고 나

항많

사및 시실 지못함

건강및 능수행 만 , 사 경만 , 심리만 및가계 만등 하역

Generic HRQOL Tools

HRQoL Instruments• Cancer-specific instruments

– Responsive to disease-related changes

– Cannot be used across populations with chronic disease

• Several are in common use because they are reliable and have been validated:

– Functional Living Index-Cancer: Shipper;JCO (1984); 2:427-483

• Modular instruments: combine a generic or “core” instrument with cancer-type specific questions

– FACT-C Gunnars, Acta Oncologica (2001);40:175-84.

– EORTC QLQ-C30, Aaronson JNCI (1993);85:365-367.

도 CARES FACT-G FLIC EORTC QLQ-30 RSCL

신 , 신체 사(clinical & research)

functional state, well being

치료법에라 functional res

ponse 차 가는지사

Clinical trial 에health ou

tcome 사

Clinical research에참여한상사 .

항수

Original: 93-132항Short form: 38-57항

27 항 22 항 30 항 38 항

상시간

Long form 18 5 하 10 하 15 하 10 하

수 0~4 5 척도 5 리커트척도, 수가 수 삶질

7 척도 VAS 4 척도, 7 척도 4 척도.

한버

Validation Validation

비고 상생 과재에 , 재 , 결생 , , 가포함 질병과치료

한 상생내 포함

신체 역, 사 /가역, , 능 역 역에걸쳐포 평가

생에 반 능수 평가, 신체심리 및사능등 포

global health status 항 과 능평가항 주 상항, 에한다 가지 상항 과 가지각하는재 담항지포함하여평

가.

psychological 측과everyday activity 측 하고, 여러상 사

Generic HRQOL Tools for Cancer

HRQoL Instruments

• Domain Specific Instruments

– Designed to address one specific aspect of HRQoL

– Examples:

• Multi-dimensional Fatigue Inventory (MFI)

• McGill Pain Questionnaire

Uses of HRQoL Instruments

• Outcome measure

– RCT evaluating treatment outcomes

– To qualify quantity of survival (e.g.,cost-effectiveness)

– Assess late physical/psychological problems

• Predictor

• Intervention

• Collaboration

• Cross-cultural validation

– Permission from developer

– Translation-back translation

– Pilot study

– Confirm

– Filed testing

– Psychometric validation

Cross-cultural aspect

English Chinese United StatesPhysical Mental Physical Mental Physical Mental

PF 0.60 0.14 0.75 0.03 0.85 0.12

RP 0.85 0.12 0.78 0.25 0.81 0.27

BP 0.46 0.53 0.53 0.51 0.76 0.28

GH 0.14 0.74 0.32 0.66 0.69 0.37

VT 0.15 0.84 0.16 0.83 0.47 0.64

SF 0.49 0.56 0.48 0.56 0.42 0.67

RE 0.77 0.18 0.62 0.36 0.17 0.78

MH 0.12 0.83 0.10 0.86 0.17 0.87

SF-36 Factor Analysis in Singapore vs. US

Other Considerations

• Is the proposed analysis too taxing for the subject?

– must questionnaire be completed serially in light of possible attrition

– Is a proxy needed?

• Will population include children, low literacy, non-English speaking, visually impaired, or cognitively impaired adults?

HRQOL Assessment

Other Considerations (cont’d)

• Timing of assessments– consistency across patients/groups critical– responses influenced by recent experiences

• Missing data– avoid at all costs– generally cannot be assumed to be at random– specify methods for dealing in advance!

• Multiple comparisons– specify primary endpoints in advance

HRQOL Assessment

Make Your Final Choice

• Psychometric (responsive, valid, reproducible) properties

• Validated in your population

• Known and used in your field

HRQOL Assessment

근간 생 가

• 검진 진단 가

• 간 해 학 해

• 간 에 한병태생리 연 발

• 상진단술

• 청학 진단법 발달

• 수술방법및수술 발

하지만…다 에비해…

• 재발 & 낮 생

• 수술후간 에 한사망 험

• 여러가지합병 발생

치료가능성보다는치료 합병증을 최소화하면서

정상적인 생활을 위한간암환자의 삶의 질 측면이중요하게 인식되고 있음

삶 질평가도 (Liver cancer specific module)

CLINICAL GASTROENTEROLOGY AND HEPATOLOGY 2010;8:559–564

Physical issue

• Lower physical well-being• Lower overall HRQOL• Pain• Sleep problem• Fatigue• Nausea• Sexual problems• Loss of appetite and weight• Difficulties digesting food• Decreased ability to perform usual activities

CLINICAL GASTROENTEROLOGY AND HEPATOLOGY 2010;8:559–564

Quality of Life Research 2007;16:203-215

Physical well-being

Functional well-being

Overall quality of life

Treatment issue (TACE, RT)

Annals of Oncology 2006;17:304-312

Hepatobiliary cancer subscale

Functional Assessment of Cancer Therapy-Hepatobiliary

FACT-Hapatobiliary Symptom Index

Clinical level issueBetter Child-Puch

Classification

Higher albumin levels

Lower serum bilirubin levels

Lower serum cholinesterase levels

Advance stage

Tumor recurrence

CLINICAL GASTROENTEROLOGY AND HEPATOLOGY 2010;8:559–564

Worse HRQOL

Better HRQOL

Psychological issue

Psycho-oncology 2013;22:2372–2378

Psycho-oncology 2013;22:2372–2378

상 우울집단별 나뉘어보간 비

18.4% 가

Psycho-oncology 2013;22:2372–2378

연 참여 반 및 상 사항보 하여도 에비해간 가

3.5배 우울하다고느꼈

삶 질연 한

• 최근 연구의 부재

• 대부분의 신체적 문제와 삶의 질에 관한연구임

• 심리사회적 문제에 따른 삶의 질 영향에 관한연구가 필요함

• 신체적 문제와 심리적 문제의 관련성과이들이 환자의 삶의 질에 어떠한 영향을미치는지에 대한 연구가 필요함

Methodological Challenges

• The variety of questionnaires available

• Choice of time points

• Incomplete data (data attrition)

• Lack of pre-defined endpoints

• Response-shift over time of patient perceptions of HRQoL

• Psychological defenses tend to conserve perception of good HRQoL

1. Integration of QOL outcomes in cancer clinical trials is challenging

2. Anticipation of design, data collection, and analysis will decrease some problems

3. Additional resources are required to incorporate QOL outcomes successfully-budget for them!

CONCLUSIONS:

Despite the Uphill Climb…we’re getting there