patient-reported outcomes: introducion and overview

Patient-Reported Outcomes:

Introducion and Overview

Pythia Nieuwkerk, PhDDepartment of Medical Psychology

Academic Medical Center, Amsterdam

Outline presentation

• What are patient–reported outcomes (PROs)?– How do PROs complement traditional

clinical outcome measures?

• How can we measure PROs?– Type of measures

• How are PROs used in clinical research?– Examples

What is a Patient-Reported Outcome?

• A PRO is any report of the status of a patient’s health condition that comes directly from the patient– without interpretation of the patient’s

response by a clinician or anyone else.1

• The term PRO addresses the source of the report, and not the concept or content of the report.2

1. FDA, 2009, 2. Patrick et al. 2007

What concepts do PRO instruments measure?

• Concepts measured by PROs differ in their degree of complexity:– From simple

•eg, presence of a symptom

– To more complex concepts •eg, ability to carry out activities of

daily living

– To even more complex concepts •eg, health-related quality of life

What is health-related quality of life?

Health:

A state of complete physical, social, and mental well-being, not merely the absence of disease or infirmity

WHO, 1948

WHO-based consensus of “Quality of Life”

MentalMentalFunctioningFunctioning

PhysicalPhysicalFunctioningFunctioning

Social Functioning

Multi-dimensionalMulti-dimensional

SubjectiveAffected by disease/treatment

Subjectivity and Objectivity

• HRQoL is not subjective in the usual sense of the term

• It can be measured accurately in an individual, and in a group

• It is “subjective” in that it:– derives from the individual

patient.– represents what is important to

the individual patient.

How do PROs complement traditional clinical

outcome measures?

WILSON-CLEARY MODEL OF HEALTH OUTCOMES

Characteristics of Individual

Biological and

Physiological

Variables

SymptomsFunctional

Status

General Health

Perceptions

Quality of Life

Characteristics of Environment

Wilson & Cleary JAMA (1995)

Motivations for PRO/QOL research

• Changing the concept of treatment model– Switching from biomedical model

to patient-centered model– Living longer and comfortable,

especially for cancer patients, elderly population, etc.

Number of papers on “quality of life” published each year (PubMed)

1970 1975 1980 1985 1990 1995 2000 2005

Motivations for PRO/QOL research

• Some treatment effects are known only to the patient– eg, pain intensity and fatigue

• Capturing different aspects of health outcomes extended beyond biomedical / clinical indicators – eg, symptoms and functioning,

comprehensive assessment of impact of disease and treatment

When are PROs most relevant

• When no survival gain is expected (e.g. palliative treatments)

• When no significant differences in survival are expected

• Where survival is gained at the expense of major toxicity and treatment burden

How can we measure PROs?

www.proqolid.orgwww.proqolid.org

Type of health outcomes instrument

HEALTH PROFILEHealth states and impact on

daily functioning and well-being

Generic measure

Disease-specificmeasure

SF-36WHOQOL-100

MOS-HIV EORTC QLQ C30

Generic instrument- SF-36

Health profile: 8 domains

• Physical functioning (10 items)

• Role limitations/physical (4 items)

• Role limitations/emotional (3 items)

• Social functioning (2 items)

• Emotional well-being (5 items)

• Energy/fatigue (4 items)

• Pain (2 items)

• General health perceptions (5 items)

Does your health now limit you

in walking more than a mile? (If so, how much?)

No, not limited at all

Yes, limited a little

Yes, limited a lot

How much of the time during the

past 4 weeks have you been happy?

None of the timeA little of the

timeSome of the timeMost of the timeAll of the time

Physical Health

Physical functionPhysical function

Role function-physical

PainPain General Health

General Health

SF-36 Physical Health

SF-36 Mental Health

Mental HealthMental Health

Emotional Well-BeingEmotional Well-Being

Role function-emotional

EnergyEnergy Social functionSocial

function

Generic instrument – WHOQOL-100

Health profile: 6 domains

• Physical health (12 items)

• Psychological health (20 items)

• Level of independence (16 items)

• Social relationship (12 items)

• Environment (32 items)

• Spirituality, religiousness & personal beliefs (4 items)

Same domain, different content

Social domain:

Social functioning versus social well being

• Social functioning: limitations due to disease/treatment (SF36, EORTC-QLQ-C30)

– More likely to respond to medical treatment

• Social wellbeing: closeness with family and friends (FACT-G)

– More likely to respond to psychosocial interventions

Generic versus Disease specific PROs

Generic PRO• Intended for use across broad

chronic disease populations• Allow comparisons across these

groups • Disadvantage: may not permit

adequate disease-specific focus–Disease caused symptoms–Treated related symptoms

RELATIVE DISEASE BURDEN: Generic PROs allow for cross-disease

comparison of disease impact

30 34 36 40 50 55

Average Adult

Average Well Adult

SF-36’s Physical Component Summary (PCS)

Type-2 Diabetes

Depression

Congestive Heart Failure

Chronic Lung

DiseaseAsthma

Ware & Kosinski, 2001Ware & Kosinski, 2001

Generic versus Disease specific PROs

Disease specific PRO• Focus on the impact of a particular

condition on the patient’s functioning and experience

• Responsive to disease-related changes

• Cannot be used across populations with other diseases

WILSON-CLEARY MODEL OF HEALTH OUTCOMES

Characteristics of Individual

Biological and

Physiological

Variables

SymptomsFunctional

Status

General Health

Perceptions

Quality of Life

Characteristics of Environment

Wilson & Cleary JAMA (1995)

Combining PRO measures

Disease-specific and Generic PROs are complementary:

• When both are included in a study, it is possible to capture:– Disease-specific concepts– Generic concepts, compare to norm:

(relative) burden of illness / benefit of treatment

Measuring PROs/HRQL

• No standard scale, need to specify what we want to measure– What is your research question?– Who are your patients?– What do you anticipate what will happen?

• Appropriateness of the measure to the question or issue of concern.

• Correspondence between the content of the measure and goals of the study.

How are PROs used in clinical research?

• Characterizing the burden of disease and treatment

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

• Predicting patient outcomes

• Evaluating the effectiveness of interventions

Study Goals

Functional scales

Physical functioning

Role functioning

Cognitive functioning

Social functioning

Emotional functioning

The EORTC QLQ-C30

Functional scales

Role functioning

Social functioning

Fatigue

Nausea and Vomiting

Dyspnea

Insomnia

Appetite loss

Constipation

Diarrhea

Financial difficulties

Symptoms

The EORTC QLQ-C30

Functional scales

Role functioning

Social functioning

Fatigue

Nausea and Vomiting

Dyspnea

Insomnia

Appetite loss

Constipation

Diarrhea

Symptoms

Global health status

Overall QoL

Global health status scale

The EORTC QLQ-C30

Functional scales

Role functioning

Social functioning

Fatigue

Nausea and Vomiting

Dyspnea

InsomniaAppetite loss

Constipation

Diarrhea

Symptoms

Overall QoL

ge 0 - 100

Standardized score

The EORTC QLQ-C30

Functional scales

Role functioning

Social functioning

Fatigue

Nausea and Vomiting

Dyspnea

Insomnia

Appetite loss

Constipation

Diarrhea

Symptoms

Overall QoL

ge 0 - 100

Standardized score

The EORTC QLQ-C30

A higher score

indicates a higher

level of functioning

A higher score

indicates a higher

level of symptoms

A higher score

indicates a

higher

level of QoL

0 = Poor QOL0 = Poor QOL71

Role functioning

Social functioning

Fatigue

Nausea and Vomiting

Dyspnea

Insomnia

Appetite loss

Constipation

Diarrhea

Healthy women (50-59 years) (Schwarz et al. Eur J Cancer, 2001)

Metastatic breast cancer baseline (Bottomley et al 2003)

Metastatic breast cancer at cycle 2 of doxorubicin/cyclophosphamide

100 = Many 100 = Many symptomssymptoms

O= No O= No symptomssymptoms

100 = 100 = Good QOLGood QOL

Profiles

Study Goals

Changes in HRQL from start to 18 months of antiretroviral therapy for HIV-infection

asymptomatic

symptomatic

• Ccharacterizing the burden of disease and treatment

Study Goals

Predicting survival in HIV infection

• 560 HIV infected patients starting HAART.• Completed the MOS HIV between 1998-2000.• All cause mortality established in March

2008.• 66 patients (11.8%) died during follow-up.• Physical Health Summary score (MOS HIV)

significant predictor of survival, independent of other (clinical) parameters.

de Boer-van der Kolk: CID 2010de Boer-van der Kolk: CID 2010

Physical Health summary score (MOS-HIV)

de Boer-van der Kolk: CID 2010de Boer-van der Kolk: CID 2010

Predicting Outcomes

• Baseline HRQL has been shown to be an independent predictor for overall survival– Overview of 36 trials that assessed baseline

PROs and mortality (Gotay, JCO 26:1355, 2009) • PRO is a complex biomarker that can be

highly predictive– Help signal those patients who are in need of

medical attention– Can be an early warning useful for clinical

decision making– Can be used as a stratification variable in

research

Study Goals

VITAL study VITAL study Prevention of Coronary Heart Prevention of Coronary Heart

DiseaseDisease

Intervention to enhance adherence Intervention to enhance adherence to statin therapy and life-style to statin therapy and life-style

recommendationsrecommendations

• Protocolized (nurse practitioner).

• Identification individual risk factors.

• Calculation Absolute Cardiovascular Risk (Framingham risk score)

• Graphical presentation personal risk Risk Passport.

• Life style counseling (stop smoking, weight reduction)

RRisk isk ccounselingounseling

RRisk Passportisk Passport

Your risk Target

Standard

10- year CVD risk

Inclusion CriteriaInclusion Criteria• > 18 yrs• Indication for statin

therapy- primary preventionsecondary prevention

Subjects

(n = 201, from outpatient clinics)

Study endpoints

• Primary endpointsPrimary endpoints– LDL cholesterol levelsLDL cholesterol levels– Adherence to statinsAdherence to statins– AnxietyAnxiety

• Secondary Secondary endpointendpoint– Quality of Life (QOL)Quality of Life (QOL)

• Adherence to statins:Adherence to statins:Please estimate the percentage of Please estimate the percentage of prescribed lipid lowering medication prescribed lipid lowering medication that you have taken during the last that you have taken during the last monthmonth– 9 point scale (<30% to 100%)9 point scale (<30% to 100%)

• Anxiety (HADS)Anxiety (HADS)• Quality of Life (SF-12)Quality of Life (SF-12)

00 33 99 1818(month)(month)

QuestionnaireWeight, RR

LDL cholesterol

risk counselingrisk counselingrisk calculationrisk calculation

LDL cholesterol

risk counselingrisk calculation

LDL cholesterol

LLDL cholesterol

Extended careExtended care

LDL cholesterol

LLDL cholesterol

Routine careRoutine care

Result: LDL cholesterol

0 2 4 6 8 10 12 14 16 18

months from start intervention

0 2 4 6 8 10 12 14 16 18

Primary preventionPrimary prevention Secondary preventionSecondary prevention

Extended careExtended care Routine careRoutine care

Results: Anxiety and adherence

0 2 4 6 8 10 12 14 16 18

Results: HRQL

0 2 4 6 8 10 12 14 16 18

Summary

• PROs can be used to assess the impact of disease and treatment from the patient perspective.

• Various PRO measures are available from which you can choose depending on your study goals.

• PROs can complement traditional clinical outcome measures when applied in clinical research.

patient-reported outcomes: introducion and overview

individual patient

patientreported outcomes

patients health condition

complex concepts

clinical research

biomedical clinical

patientcentered modelliving

biomedical model

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