Patient-Reported Outcomes:
Introducion and Overview
Pythia Nieuwkerk, PhD
Department 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”
Multi-dimensional
Physical
Functioning
Social
Functioning
Mental
Functioning
Affected by disease/treatment
Subjective
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
Symptoms
Functional
Status
General
Health
Perceptions
Characteristics of Environment
Wilson & Cleary JAMA (1995)
Quality of
Life
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)
11000
10000
9000
8000
7000
6000
5000
4000
3000
2000
1000
0
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.org
Type of health outcomes instrument
HEALTH PROFILE
Health states and impact on
daily functioning and well-being
Generic
measure
SF-36
WHOQOL-100
Disease-specific
measure
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 time
A little of the time
Some of the time
Most of the time
All of the time
SF-36 Physical Health
Physical Health
Physical
function
Role
functionphysical
Pain
General
Health
SF-36 Mental Health
Mental Health
Emotional
Well-Being
Role
functionemotional
Energy
Social
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
Type-2
Diabetes
Depression
Congestive
Heart
Failure
Chronic
Lung
Disease
30
34 36
Asthma
40
Average
Adult
Average
Well
Adult
50
55
SF-36’s Physical Component Summary (PCS)
Ware & 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
Symptoms
Functional
Status
General
Health
Perceptions
Characteristics of Environment
Wilson & Cleary JAMA (1995)
Quality of
Life
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?
Study Goals
• 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
The EORTC QLQ-C30
Physical functioning
Role functioning
Functional scales
Cognitive functioning
Emotional functioning
Social functioning
The EORTC QLQ-C30
Physical functioning
Role functioning
Functional scales
Cognitive functioning
Emotional functioning
Social functioning
Fatigue
Nausea and Vomiting
Pain
Symptoms
Dyspnea
Insomnia
Appetite loss
Constipation
Diarrhea
Financial difficulties
The EORTC QLQ-C30
Physical functioning
Role functioning
Functional scales
Cognitive functioning
Emotional functioning
Social functioning
Fatigue
Nausea and Vomiting
Pain
Symptoms
Dyspnea
Insomnia
Appetite loss
Constipation
Diarrhea
Financial difficulties
Global health
status scale
Global health status
Overall QoL
The EORTC QLQ-C30
Physical functioning
Standardized score
Role functioning
Functional scales
Cognitive functioning
Emotional functioning
Social functioning
Nausea and Vomiting
Pain
Symptoms
Dyspnea
Insomnia
Appetite loss
Constipation
Diarrhea
Financial difficulties
Global health
status scale
Global health status
Overall QoL
Range 0 - 100
Fatigue
The EORTC QLQ-C30
Physical functioning
Standardized score
Role functioning
Functional scales
A higher score
Cognitive functioning
indicates a higher
Emotional functioning
level of functioning
Social functioning
Nausea and Vomiting
Pain
Symptoms
Dyspnea
Insomnia
Appetite loss
Constipation
Range 0 - 100
Fatigue
A higher score
indicates a higher
level of symptoms
Diarrhea
Financial difficulties
A higher score
indicates a
Global health
status scale
Global health status
Overall QoL
higher
level of QoL
Functional scales
100 =
96 Good QOL
71
Physical functioning
63
Role functioning
93
83
Cognitive functioning
62
Emotional functioning
71
64
Global health status
14
38
Fatigue
Nausea and Vomiting
2
10
14
Pain
6
Dyspnea
4
Appetite loss
Diarrhea
28
34
14
Insomnia
Constipation
31
2
20
11
4
7
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
94
77
Social functioning
O= No
symptoms
Symptoms scales
Profiles
0 = Poor QOL
91
71
100 = Many
symptoms
Study Goals
• 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
-5
Overall QoL
Mental health
General health
Health distress
Vitality
Pain
Cognitive function
Social function
Role function
Physical function
Mean QoL change-score
Changes in HRQL from start to 18
months of antiretroviral therapy for
HIV-infection
30
25
20
15
asymptomatic
10
symptomatic
5
0
Study Goals
• 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
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 2010
Physical Health summary score (MOS-HIV)
de 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
• 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
VITAL study
Prevention of Coronary Heart
Disease
Intervention to enhance adherence to
statin therapy and life-style
recommendations
Risk counseling
• 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)
Risk Passport
25
20
15
10-year CVD risk
10
5
0
Your risk
Target
Standard
risk
risk
Subjects
(n = 201, from outpatient clinics)
Inclusion Criteria
• > 18 yrs
• Indication for statin
therapy
- primary prevention
- secondary prevention
Study endpoints
• Primary endpoints
– LDL cholesterol levels
– Adherence to statins
– Anxiety
• Secondary endpoint
– Quality of Life (QOL)
PROs
• Adherence to statins:
Please estimate the percentage of
prescribed lipid lowering medication
that you have taken during the last
month
– 9 point scale (<30% to 100%)
• Anxiety (HADS)
• Quality of Life (SF-12)
Routine care
Questionnaire
Weight, RR
LDL cholesterol
0
Questionnaire
Weight, RR
LDL cholesterol
3
Questionnaire
Weight, RR
LDL cholesterol
Questionnaire
Weight, RR
LLDL cholesterol
9
18
(month)
Questionnaire
Weight, RR
LDL cholesterol
Questionnaire
Weight, RR
LDL cholesterol
Questionnaire
Weight, RR
LDL cholesterol
Questionnaire
Weight, RR
LLDL cholesterol
risk counseling
risk calculation
risk counseling
risk calculation
risk counseling
risk calculation
risk counseling
risk calculation
Extended care
Result: LDL cholesterol
Secondary prevention
Primary prevention
5
5
4
LDL-c mmol/L
LDL-c mmol/L
4
3
2
1
0
3
2
1
0
2
4
6
8
10 12 14
months from start intervention
Extended care
16
18
Routine care
0
0
2
4
6
8
10 12 14
months from start intervention
16
18
Results: Anxiety and adherence
7
5
4
3
10
2
1
0
0
2
4
6
8
10
12
14
16
months from start intervention
Extended care
Routine care
18
Adherence to statins (%) last month
Anxiety (HADS)
6
9
8
7
6
5
4
3
2
1
0
0
2
4
6
8
10 12 14
months from start intervention
16
18
Results: HRQL
40
30
20
10
0
0
2
4
6
8
10 12 14
months from start intervention
Extended care
16
Routine care
18
Physical Health Summary score
Mental Health Summary score
50
50
40
30
20
10
0
0
2
4
6
8
10 12 14
months from start intervention
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.