Patient-Reported Outcomes: Introducion and Overview

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Patient-Reported OutcomesIntroducion and
Overview

• Pythia Nieuwkerk, PhD
• Department of Medical Psychology
• Academic Medical Center, Amsterdam

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Outline presentation

• What are patientreported 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

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What is a Patient-Reported Outcome?

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

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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

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WHO-based consensus of Quality of Life
Multi-dimensional
Physical Functioning
Social Functioning
Mental Functioning
Affected by disease/treatment
Subjective
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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.

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How do PROs complement traditional clinical
outcome measures?
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WILSON-CLEARY MODEL OF HEALTH OUTCOMES
Characteristics of Individual
Biological and Physiological Variables
Symptoms
Functional Status
General Health Perceptions
Quality of Life
Characteristics of Environment
Wilson Cleary JAMA (1995)
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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.

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

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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

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How can we measure PROs?
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www.proqolid.org
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Type of health outcomes instrument
HEALTH PROFILE Health states and impact on daily
functioning and well-being
Generic measure
Disease-specific measure
SF-36 WHOQOL-100
MOS-HIV EORTC QLQ C30
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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)

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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

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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

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SF-36 Physical Health
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SF-36 Mental Health
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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)

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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

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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

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RELATIVE DISEASE BURDEN Generic PROs allow for
cross-disease comparison of disease impact
Ware Kosinski, 2001
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Generic versus Disease specific PROs

• Disease specific PRO
• Focus on the impact of a particular condition on
  the patients functioning and experience
• Responsive to disease-related changes
• Cannot be used across populations with other
  diseases

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WILSON-CLEARY MODEL OF HEALTH OUTCOMES
Characteristics of Individual
Biological and Physiological Variables
Symptoms
Functional Status
General Health Perceptions
Quality of Life
Characteristics of Environment
Wilson Cleary JAMA (1995)
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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

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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.

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How are PROs used in clinical research?
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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

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(No Transcript)
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The EORTC QLQ-C30
Physical functioning
Role functioning
Functional scales
Cognitive functioning
Emotional functioning
Social functioning
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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
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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
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The EORTC QLQ-C30
Standardized score
Physical functioning
Role functioning
Range 0 - 100
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
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The EORTC QLQ-C30
Standardized score
Physical functioning
Role functioning
Range 0 - 100
A higher score indicates a higher level of
functioning
Functional scales
Cognitive functioning
Emotional functioning
Social functioning
Fatigue
Nausea and Vomiting
Pain
Symptoms
A higher score indicates a higher level of
symptoms
Dyspnea
Insomnia
Appetite loss
Constipation
Diarrhea
Financial difficulties
A higher score indicates a higher level of QoL
Global health status scale
Global health status
Overall QoL
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Profiles
100 Good QOL
0 Poor QOL
71
96
Physical functioning
63
93
Role functioning
83
94
Cognitive functioning
Functional scales
62
Emotional functioning
77
71
Social functioning
91
64
Global health status
71
O No symptoms
100 Many symptoms
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38
Fatigue
2
10
Nausea and Vomiting
14
31
Pain
6
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Dyspnea
Symptoms scales
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14
Insomnia
4
20
Appetite loss
11
2
Constipation
4
7
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
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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

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Changes in HRQL from start to 18 months of
antiretroviral therapy for HIV-infection
Cognitive function
Physical function
Social function
Health distress
General health
Role function
Mental health
Overall QoL
Vitality
Pain
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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

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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
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Physical Health summary score (MOS-HIV)
de Boer-van der Kolk CID 2010
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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 261355, 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

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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

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VITAL study Prevention of Coronary Heart
Disease

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

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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)

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Risk Passport
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Subjects
(n 201, from outpatient clinics)

• Inclusion Criteria
• gt 18 yrs
• Indication for statin therapy- primary
  prevention- secondary prevention

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Study endpoints

• Primary endpoints
• LDL cholesterol levels
• Adherence to statins
• Anxiety
• Secondary endpoint
• Quality of Life (QOL)

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PROs

• Adherence to statins
• Please estimate the percentage of prescribed
  lipid lowering medication that you have taken
  during the last month
• 9 point scale (lt30 to 100)
• Anxiety (HADS)
• Quality of Life (SF-12)

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Routine care
Questionnaire Weight, RR LDL cholesterol
Questionnaire Weight, RR LDL cholesterol
Questionnaire Weight, RR LDL cholesterol
Questionnaire Weight, RR LLDL cholesterol
0 3 9 18(month)
Questionnaire Weight, RR LDL cholesterol risk
counseling risk calculation
Questionnaire Weight, RR LDL cholesterol risk
counseling risk calculation
Questionnaire Weight, RR LDL cholesterol risk
counseling risk calculation
Questionnaire Weight, RR LLDL cholesterol risk
counseling risk calculation
Extended care
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Result LDL cholesterol
Primary prevention
Secondary prevention
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Results Anxiety and adherence
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Results HRQL
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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.