Transcript Everything You Ever Wanted to Know About PROs (and Perhaps Even More) Amylou C.

Everything You Ever
Wanted to Know
About PROs
(and Perhaps Even More)
Amylou C. Dueck, PhD
Mayo Clinic Arizona &
NCCTG
CRA Workshop for Cancer Control Studies
November 14, 2009
Outline
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What are PROs?
What are the different types of PROs?
Why do we measure PROs?
How do we measure PROs?
Why do we measure PROs the way that we do?
Why are there different instruments measuring the same thing?
How are these measures created?
What can PROs tell us?
Why is it so important that they be administered as specified in
protocols?
Why is the CRA role so important?
Are there respondent burden issues?
What are PROs?
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PRO = Patient-reported outcome
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Definition from FDA Draft Guidance:
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“a 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).”
http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegula
toryInformation/Guidances/ucm071975.pdf
Or Google “FDA draft guidance patient reported-outcomes”
Definition from Wikipedia:
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“PRO is an umbrella term that covers a whole range of potential
types of measurement but is used specifically to refer to
questionnaires completed by the patient.”
http://en.wikipedia.org/wiki/Patient-reported_outcome
What are the different types of
PROs?
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Health-related quality of life (HRQOL)
Quality of life (QOL)
Symptoms
Functioning
Satisfaction
Decision-making / preferences
Treatment compliance
Health utilities
Others???
Why do we measure PROs?
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PROs are key to providing a better
understanding of treatment outcomes, beyond
the data obtained from clinical assessments
PROs have become to gold standard for
assessing subjective experiences of patients
To get the patient’s perspective!
How do we measure PROs?
INSTRUMENTS
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European Organisation for Research and Treatment of Cancer
Quality of Life Questionnaire Core 30 (EORTC QLQ-C30)
 Disease modules such as the Breast (BR23)
 http://groups.eortc.be/qol/index.htm
http://www.mdanderson.org/education-andresearch/departments-programs-and-labs/departments-anddivisions/symptom-research/symptom-assessmenttools/index.html
 Brief Pain Inventory (BPI)
 Brief Fatigue Inventory (BFI)
 MD Anderson Symptom Inventory (MDASI)
Functional Assessment of Cancer Therapy General (FACT-G)
 Disease specific (FACT-B), disease/symptom specific
(FBSI), symptom specific (FACT-An), treatment specific
(FACT-Taxane)
 http://www.facit.org/
How do we measure PROs?
INSTRUMENT REPOSITORIES
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Databases of instruments
 QOLID
 http://www.proqolid.org/
 OLGA
 http://www.olga-qol.com/index.html
 Australian Centre on Quality of Life
 http://acqol.deakin.edu.au/instruments/index.ht
m
 American Thoracic Society Quality of Life
Resource
 http://www.atsqol.org/sections/instruments/inde
x.html
EORTC QLQ-C30
EQ-5D
Brief Pain Inventory
Short Form
Wong-Baker FACES Pain Scale
How do we measure PROs?
MODES OF ADMINISTRATION
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Paper
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In clinic
Take-home
Interview (in person)
Interview (telephone)
ePROs (electronic data capture of PROs)
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Digital pen
Wireless tablet
Smart phone
Telephone = Interactive Voice Response System (IVRS)
Web
Paper
Web
IVRS: http://www.perceptive.com/files/flash/diary2.swf
Wireless tablet
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http://www.invivodata.com/media/swf/Demo.swf
Why do we measure PROs the way
that we do?
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Much work goes into instrument development
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Need to make sure that the questionnaire is
measuring what you think it is measuring
Need to make sure that patients are interpreting
questions as intended
Need to make sure that the instrument is sensitive
to change (but also produces similar results if
nothing has changed)
Need to know the size of a clinically meaningful
change or difference
Why are there different instruments
measuring the same thing?
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Independent groups developed instruments to
fit their own needs
Instruments vary in level of detail and intended
population
How are these measures created?
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May involve some or all of these steps:
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Conceptual framework
Item generation (literature, expert opinion, patient
focus groups, online chat rooms/blogs, etc.)
Cognitive interviews
Feasibility testing
Validation study
What can PROs tell us?
Single-item overall QOL at baseline is prognostic of survival in cancer
patients! Even after adjusting for performance status!
Median Survival
(Months)
Median (95% CI)
Log-rank
P-value
nCD
QOL CD
9.3 (8.1, 10.6)
0.0001
QOL nCD
16.8 (16.1, 17.4)
CD
Tan AD, Novotny PJ, et al. A patient-level meta-analytic investigation of the prognostic significance of baseline
quality of life (QOL) for overall survival (OS) among 3,704 patients participating in 24 North Central Cancer
Treatment Group (NCCTG) and Mayo Clinic Cancer Center (MC) oncology clinical trials. J Clin Oncol 26: 2008
(May 20 suppl; abstr 9515), ASCO 2008.
So is single-item fatigue! Even after
adjusting for overall QOL and
performance status!
100
90
80
nCF
% Alive
70
60
50
Median Survival
(Months)
Median (95% CI)
40
30
20
Fatigue CF
31.5 (25.9, 42.4)
10
Fatigue nCF
>83.9 (NA)
Log-rank
P-value
CF
0.0001
0
0
1
2
3
4
5
Survival Time(Years)
Sloan JA, Liu H, et al. A patient-level pooled analysis of the prognostic significance of baseline fatigue for overall
survival (OS) among 3,915 patients participating in 43 North Central Cancer Treatment Group (NCCTG) and Mayo
Clinic Cancer Center (MC) oncology clinical trials. J Clin Oncol 27:15s, 2009 (suppl; abstr 9599), ASCO 2009.
Some things are just better
measured by the patient!
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Hot flash studies (women and men)
“Aren’t hot flashes better measured by a device which
measures skin conductance? How do you know that the patient
is really having a hot flash?”
And in response, the famous words of one NCCTG
investigator: “I wouldn’t want to be the one to tell a woman
that she’s not having a hot flash.”
Mean Hot Flash Score Reduction
Randomized Studies
100
% Reduction (Mean)
Black Cohosh (n=58)
80
Placebo (n=420)
Soy (n=78)
Vitamin E (n=53)
Clonidine (n=75)
Fluoxetine (n=36)
60
Ven (vs MPA) (n=94)
Venlafaxine (n=48)
40
MPA 400 mg (n=94)
20
Megestrol (n=74)
MPA 500 mg X 3(n=7)
0
0
1
2
3
4
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6
Week
Loprinzi CL, Barton DL, et al. Mayo Clinic and North Central Cancer Treatment Group hot flash
studies: a 20-year experience. Menopause 2008; 15(4):655-660.
Why is it so important that they be
administered as specified in protocols?
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May see things like:
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Administer baseline patient assessment prior to notifying
patient of his/her randomization assignment
Administer onstudy patient assessment prior to discussing
outcome of disease assessment
Administer in a private room or a quite area in a waiting
room with adequate privacy
Why?
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Avoid bias
Increase compliance / patient willingness
Consistency across sites, patients, visits
Why is the CRA role so important?
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I wouldn’t have any data without CRAs!
Data quality and quantity is directly impacted by the
CRA
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Follow protocol
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Check duplication quality of questionnaires
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Administration guidelines and test schedule
Missing pages?
Professional-looking copies => better patient compliance
Answer patient questions
Even with ePROs
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Administration
Patient questions
Are there respondent burden issues?
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YES!!!
We’ve all filled out questionnaires from time
to time – how long does the survey have to be
for you to say “FORGET IT!”???
For cancer patients: ≤50 items
Questions?
Contact info:
Amylou Dueck
[email protected]