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 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? PRO = Patient-reported outcome Definition from FDA Draft Guidance: “a measurement of any aspect of a patient’s health status that comes directly from the patient (i.e., without the interpretation of the patient’s responses by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 http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm071975.pdf Or Google “FDA draft guidance patient reported-outcomes” Definition from Wikipedia: “PRO is an umbrella term that covers a whole range of potential types of measurement but is used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? 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? 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 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-and-research/departments-programs-and-labs/departments-and-divisions/symptom-research/symptom-assessment-tools/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 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.htm American Thoracic Society Quality of Life Resource http://www.atsqol.org/sections/instruments/index.html

EORTC QLQ-C30

EQ-5D

Brief Pain Inventory Short Form

Wong-Baker FACES Pain Scale

How do we measure PROs? MODES OF ADMINISTRATION Paper In clinic Take-home Interview (in person) Interview (telephone) ePROs (electronic data capture of PROs) 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 http://www.invivodata.com/media/swf/Demo.swf

Why do we measure PROs the way that we do? Much work goes into instrument development 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? Independent groups developed instruments to fit their own needs Instruments vary in level of detail and intended population

How are these measures created? May involve some or all of these steps: Conceptual framework Item generation (literature, expert opinion, patient focus groups, online chat rooms/blogs, etc.) Cognitive interviews Feasibility testing Validation study

Median Survival (Months) Median (95% CI) 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 QOL CD 9.3 (8.1, 10.6) 0.0001 QOL nCD 16.8 (16.1, 17.4) nCD 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 So is single-item fatigue! Even after adjusting for overall QOL and performance status! 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! 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.”

Black Cohosh (n=58) Placebo (n=420) Soy (n=78) Vitamin E (n=53) Clonidine (n=75) Fluoxetine (n=36) Ven (vs MPA) (n=94) Venlafaxine (n=48) MPA 400 mg (n=94) Megestrol (n=74) 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 administered as specified in protocols? May see things like: 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? Avoid bias Increase compliance / patient willingness Consistency across sites, patients, visits

Why is the CRA role so important? I wouldn’t have any data without CRAs! Data quality and quantity is directly impacted by the CRA Follow protocol Administration guidelines and test schedule Check duplication quality of questionnaires Missing pages? Professional-looking copies => better patient compliance Answer patient questions Even with ePROs Administration Patient questions

Are there respondent burden issues? 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 dueck@mayo.edu