everything you ever wanted to know about pros (and perhaps even more) amylou c. dueck, phd mayo...
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Everything You Ever Everything You Ever Wanted to Know Wanted to Know
About PROsAbout PROs(and Perhaps Even More)(and Perhaps Even More)
Amylou C. Dueck, PhDAmylou C. Dueck, PhDMayo Clinic Arizona &Mayo Clinic Arizona &
NCCTGNCCTG
CRA Workshop for Cancer Control StudiesCRA Workshop for Cancer Control StudiesNovember 14, 2009November 14, 2009
OutlineOutline What are PROs?What are PROs? What are the different types of PROs?What are the different types of PROs? Why do we measure PROs?Why do we measure PROs? How do we measure PROs?How do we measure PROs? Why do we measure PROs the way that we do?Why do we measure PROs the way that we do? Why are there different instruments measuring the same Why are there different instruments measuring the same
thing?thing? How are these measures created?How are these measures created? What can PROs tell us?What can PROs tell us? Why is it so important that they be administered as specified Why is it so important that they be administered as specified
in protocols?in protocols? Why is the CRA role so important?Why is the CRA role so important? Are there respondent burden issues?Are there respondent burden issues?
What are PROs?What are PROs? PRO = Patient-reported outcomePRO = Patient-reported outcome
Definition from FDA Draft Guidance:Definition from FDA Draft Guidance: ““a measurement of any aspect of a patient’s health status that a measurement of any aspect of a patient’s health status that
comes directly from the patient (i.e., without the interpretation of comes directly from the patient (i.e., without the interpretation of the patient’s responses by a physician or anyone else).”the patient’s responses by a physician or anyone else).”
http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm071975.pdf
Or Google “FDA draft guidance patient reported-outcomes”Or Google “FDA draft guidance patient reported-outcomes”
Definition from Wikipedia:Definition from Wikipedia: ““PRO is an umbrella term that covers a whole range of potential PRO is an umbrella term that covers a whole range of potential
types of measurement but is used specifically to refer to types of measurement but is used specifically to refer to questionnaires completed by the patient.”questionnaires completed by the patient.”
http://en.wikipedia.org/wiki/Patient-reported_outcomehttp://en.wikipedia.org/wiki/Patient-reported_outcome
What are the different types of What are the different types of PROs?PROs?
Health-related quality of life (HRQOL)Health-related quality of life (HRQOL) Quality of life (QOL)Quality of life (QOL) SymptomsSymptoms FunctioningFunctioning SatisfactionSatisfaction Decision-making / preferencesDecision-making / preferences Treatment complianceTreatment compliance Health utilitiesHealth utilities Others???Others???
Why do we measure PROs?Why do we measure PROs?
PROs are key to providing a better PROs are key to providing a better understanding of treatment outcomes, beyond understanding of treatment outcomes, beyond the data obtained from clinical assessmentsthe data obtained from clinical assessments
PROs have become to gold standard for PROs have become to gold standard for assessing subjective experiences of patientsassessing subjective experiences of patients
To get the patient’s perspective!To get the patient’s perspective!
How do we measure PROs?How do we measure PROs?INSTRUMENTSINSTRUMENTS
European Organisation for Research and Treatment of Cancer European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30)Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Disease modules such as the Breast (BR23)Disease modules such as the Breast (BR23) http://groups.eortc.be/qol/index.htmhttp://groups.eortc.be/qol/index.htm
http://www.mdanderson.org/education-and-research/departments-http://www.mdanderson.org/education-and-research/departments-programs-and-labs/departments-and-divisions/symptom-research/programs-and-labs/departments-and-divisions/symptom-research/symptom-assessment-tools/index.htmlsymptom-assessment-tools/index.html Brief Pain Inventory (BPI)Brief Pain Inventory (BPI) Brief Fatigue Inventory (BFI)Brief Fatigue Inventory (BFI) MD Anderson Symptom Inventory (MDASI)MD Anderson Symptom Inventory (MDASI)
Functional Assessment of Cancer Therapy General (FACT-G)Functional Assessment of Cancer Therapy General (FACT-G) Disease specific (FACT-B), disease/symptom specific (FBSI), Disease specific (FACT-B), disease/symptom specific (FBSI),
symptom specific (FACT-An), treatment specific (FACT-Taxane)symptom specific (FACT-An), treatment specific (FACT-Taxane) http://www.facit.org/http://www.facit.org/
How do we measure PROs?How do we measure PROs?INSTRUMENT REPOSITORIESINSTRUMENT REPOSITORIES
Databases of instrumentsDatabases of instruments QOLIDQOLID
http://www.proqolid.org/http://www.proqolid.org/ OLGAOLGA
http://www.olga-qol.com/index.htmlhttp://www.olga-qol.com/index.html Australian Centre on Quality of LifeAustralian Centre on Quality of Life
http://acqol.deakin.edu.au/instruments/index.htmhttp://acqol.deakin.edu.au/instruments/index.htm American Thoracic Society Quality of Life ResourceAmerican Thoracic Society Quality of Life Resource
http://www.atsqol.org/sections/instruments/http://www.atsqol.org/sections/instruments/index.htmlindex.html
EORTC QLQ-C30EORTC QLQ-C30
EQ-5D
Brief Pain Inventory Short Form
Wong-Baker FACES Pain ScaleWong-Baker FACES Pain Scale
How do we measure PROs?How do we measure PROs?MODES OF ADMINISTRATIONMODES OF ADMINISTRATION
PaperPaper In clinicIn clinic Take-homeTake-home
Interview (in person)Interview (in person) Interview (telephone)Interview (telephone) ePROs (electronic data capture of PROs)ePROs (electronic data capture of PROs)
Digital penDigital pen Wireless tabletWireless tablet Smart phoneSmart phone Telephone = Interactive Voice Response System (IVRS)Telephone = Interactive Voice Response System (IVRS) WebWeb
PaperPaper
WebWeb
IVRS: http://www.perceptive.com/files/flash/diary2.swfIVRS: http://www.perceptive.com/files/flash/diary2.swf
Wireless tabletWireless tablet
http://www.invivodata.com/media/swf/Demo.swfhttp://www.invivodata.com/media/swf/Demo.swf
Why do we measure PROs the way Why do we measure PROs the way that we do?that we do?
Much work goes into instrument developmentMuch work goes into instrument development Need to make sure that the questionnaire is Need to make sure that the questionnaire is
measuring what you think it is measuringmeasuring what you think it is measuring Need to make sure that patients are interpreting Need to make sure that patients are interpreting
questions as intendedquestions as intended Need to make sure that the instrument is sensitive Need to make sure that the instrument is sensitive
to change (but also produces similar results if to change (but also produces similar results if nothing has changed)nothing has changed)
Need to know the size of a clinically meaningful Need to know the size of a clinically meaningful change or differencechange or difference
Why are there different instruments Why are there different instruments measuring the same thing?measuring the same thing?
Independent groups developed instruments to Independent groups developed instruments to fit their own needsfit their own needs
Instruments vary in level of detail and Instruments vary in level of detail and intended populationintended population
How are these measures created?How are these measures created?
May involve some or all of these steps:May involve some or all of these steps: Conceptual frameworkConceptual framework Item generation (literature, expert opinion, patient Item generation (literature, expert opinion, patient
focus groups, online chat rooms/blogs, etc.)focus groups, online chat rooms/blogs, etc.) Cognitive interviewsCognitive interviews Feasibility testingFeasibility testing Validation studyValidation study
What can PROs tell us?What can PROs tell us?
Median Survival Median Survival (Months)(Months)
Median (95% CI)Median (95% CI)
Log-rankLog-rankP-valueP-value
QOL CDQOL CD 9.3 (8.1, 10.6)9.3 (8.1, 10.6)0.00010.0001
QOL nCDQOL nCD 16.8 (16.1, 17.4)16.8 (16.1, 17.4)
nCD
CD
Single-item overall QOL at baseline is prognostic of survival in cancer patients! Even after adjusting for performance status!
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 So is single-item fatigue! Even after adjusting for overall QOL and adjusting for overall QOL and
performance status!performance status!
nCF
CF
0
10
20
30
40
50
60
70
80
90
100
0 1 2 3 4 5
Survival Time(Years)
% A
live
>83.9 (NA)
31.5 (25.9, 42.4)
Median Survival (Months)
Median (95% CI)
Fatigue nCF 0.0001Fatigue CF
Log-rankP-value
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 Some things are just better measured by the patient!measured by the patient!
Hot flash studies (women and men)Hot flash studies (women and men) ““Aren’t hot flashes better measured by a device which Aren’t hot flashes better measured by a device which
measures skin conductance? How do you know that the patient measures skin conductance? How do you know that the patient is really having a hot flash?”is really having a hot flash?”
And in response, the famous words of one NCCTG And in response, the famous words of one NCCTG investigator: “I wouldn’t want to be the one to tell a woman investigator: “I wouldn’t want to be the one to tell a woman that she’s not having a hot flash.”that she’s not having a hot flash.”
Mean Hot Flash Score Reduction Randomized Studies
0
20
40
60
80
100
0 1 2 3 4 5 6
Week
% R
edu
ctio
n (
Mea
n) Placebo (n=420)
Soy (n=78)
Clonidine (n=75)
Megestrol (n=74)
Fluoxetine (n=36)
Venlafaxine (n=48)
Vitamin E (n=53)
Black Cohosh (n=58)
Ven (vs MPA) (n=94)
MPA 400 mg (n=94)
MPA 500 mg X 3(n=7)
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 Why is it so important that they be administered as specified in protocols?administered as specified in protocols?
May see things like:May see things like: Administer baseline patient assessment prior to notifying Administer baseline patient assessment prior to notifying
patient of his/her randomization assignmentpatient of his/her randomization assignment Administer onstudy patient assessment prior to discussing Administer onstudy patient assessment prior to discussing
outcome of disease assessmentoutcome of disease assessment Administer in a private room or a quite area in a waiting Administer in a private room or a quite area in a waiting
room with adequate privacyroom with adequate privacy Why?Why?
Avoid biasAvoid bias Increase compliance / patient willingnessIncrease compliance / patient willingness Consistency across sites, patients, visitsConsistency across sites, patients, visits
Why is the CRA role so important?Why is the CRA role so important? I wouldn’t have any data without CRAs!I wouldn’t have any data without CRAs! Data quality and quantity is directly impacted by the Data quality and quantity is directly impacted by the
CRACRA Follow protocolFollow protocol
Administration guidelines and test scheduleAdministration guidelines and test schedule Check duplication quality of questionnairesCheck duplication quality of questionnaires
Missing pages?Missing pages? Professional-looking copies => better patient complianceProfessional-looking copies => better patient compliance
Answer patient questionsAnswer patient questions Even with ePROsEven with ePROs
AdministrationAdministration Patient questionsPatient questions
Are there respondent burden issues?Are there respondent burden issues?
YES!!!YES!!! We’ve all filled out questionnaires from time We’ve all filled out questionnaires from time
to time – how long does the survey have to be to time – how long does the survey have to be for you to say “FORGET IT!”???for you to say “FORGET IT!”???
For cancer patients: For cancer patients: ≤50 items≤50 items
