patient-reported outcomes: introducion and overview pythia nieuwkerk, phd department of medical...
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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)
0
1000
2000
3000
4000
5000
6000
7000
8000
9000
10000
11000
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
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
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
Physical functioning
Role functioning
Cognitive functioning
Social functioning
Emotional functioning
Fatigue
Pain
Nausea and Vomiting
Dyspnea
Insomnia
Appetite loss
Constipation
Diarrhea
Financial difficulties
Symptoms
The EORTC QLQ-C30
Functional scales
Physical functioning
Role functioning
Cognitive functioning
Social functioning
Emotional functioning
Fatigue
Pain
Nausea and Vomiting
Dyspnea
Insomnia
Appetite loss
Constipation
Diarrhea
Financial difficulties
Symptoms
Global health status
Overall QoL
Global health status scale
The EORTC QLQ-C30
Functional scales
Physical functioning
Role functioning
Cognitive functioning
Social functioning
Emotional functioning
Fatigue
Pain
Nausea and Vomiting
Dyspnea
InsomniaAppetite loss
Constipation
Diarrhea
Financial difficulties
Symptoms
Global health status
Overall QoL
Global health status scale
Ran
ge 0 - 100
Standardized score
The EORTC QLQ-C30
Functional scales
Physical functioning
Role functioning
Cognitive functioning
Social functioning
Emotional functioning
Fatigue
Pain
Nausea and Vomiting
Dyspnea
Insomnia
Appetite loss
Constipation
Diarrhea
Financial difficulties
Symptoms
Global health status
Overall QoL
Global health status scale
Ran
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
63
83
62
71
38
10
31
28
34
20
11
7
64
14
2
14
6
14
4
2
4
71
96
93
94
77
91
Physical functioning
Role functioning
Cognitive functioning
Emotional functioning
Social functioning
Fatigue
Pain
Nausea and Vomiting
Dyspnea
Insomnia
Appetite loss
Constipation
Diarrhea
Global health status
Fun
ctio
nal s
cale
s
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
Sym
ptom
s sc
ales
• 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
Changes in HRQL from start to 18 months of antiretroviral therapy for HIV-infection
-5
0
5
10
15
20
25
30
Me
an
Qo
L c
ha
ng
e-s
co
re
asymptomatic
symptomatic
Ph
ysic
al f
un
ctio
n
Ro
le f
un
ctio
n
So
cial
fu
nct
ion
Co
gn
itiv
e fu
nct
ion
Pai
n
Vit
alit
y
Hea
lth
dis
tres
s
Gen
eral
hea
lth
Men
tal
hea
lth
Ove
rall
Qo
L
• Ccharacterizing 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
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
• 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
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
0
5
10
15
20
25
Your risk Target
risk
Standard
risk
10- year CVD risk
Inclusion CriteriaInclusion Criteria• > 18 yrs• Indication for statin
therapy- primary prevention- secondary 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)
PROs
• 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
QuestionnaireWeight, RR
LDL cholesterol
risk counselingrisk calculation
QuestionnaireWeight, RR
LDL cholesterol
risk counselingrisk counselingrisk calculationrisk calculation
QuestionnaireWeight, RR
LLDL cholesterol
risk counselingrisk counselingrisk calculationrisk calculation
Extended careExtended care
QuestionnaireWeight, RR
LDL cholesterol
QuestionnaireWeight, RR
LDL cholesterol
QuestionnaireWeight, RR
LDL cholesterol
QuestionnaireWeight, RR
LLDL cholesterol
Routine careRoutine care
Result: LDL cholesterol
0 2 4 6 8 10 12 14 16 18
months from start intervention
0
1
2
3
4
5
LD
L-c
mm
ol/L
0 2 4 6 8 10 12 14 16 18
months from start intervention
0
1
2
3
4
5
LD
L-c
mm
ol/L
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
months from start intervention
0
1
2
3
4
5
6
7
An
xie
ty (
HA
DS
)
0 2 4 6 8 10 12 14 16 18
months from start intervention
0
1
2
3
4
55
6
7
8
9
1010
0
5
10
Ad
he
ren
ce
to
sta
tin
s (
%)
las
t m
on
th
Extended careExtended care Routine careRoutine care
Results: HRQL
0 2 4 6 8 10 12 14 16 18
months from start intervention
0
10
20
30
40
50
Me
nta
l He
alt
h S
um
ma
ry s
co
re
0 2 4 6 8 10 12 14 16 18
months from start intervention
0
10
20
30
40
50
Ph
ys
ica
l He
alt
h S
um
ma
ry s
co
re
Extended careExtended care Routine careRoutine care
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.
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