1. Validation Study of the Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE)
Amylou C. Dueck (Mayo Clinic) – Task 7 Lead

2. Process Weekly “Task 7” teleconferences since March 2009
Regular attendees
All sites plus NCI and FDA
Experts in validation studies
Oncologists, psychometricians, statisticians
Patient advocates
Adhoc experts
Example: Arthur Stone (advice on design of recall substudy)
Agenda and task documents available on the PRO-CTCAE Wiki
Click on “Task 7”

3. Process (con’d 1)
Literature search on validation of similar multi-symptom tools
Developed a concept document
Underwent review by a working group of the NCI’s Symptom/Quality of Life (SxQOL) Committee
Literature search on validation of similar multi-symptom tools
Memorial Symptom Assessment Scale (MSAS)
MD Anderson Symptom Inventory (MDASI)
EORTC QLQ-C30 + modules
PROMIS
Developed a concept document
Established the overall design of the study
Defined disease cohorts
Identified core items (based on review of data from multiple sources)
Assigned items to each cohort (included discussion of patient burden)
Selected clinical anchors
Developed the recall substudy (based on literature review and expert input)
Developed a comprehensive statistical analysis plan
Underwent review by a working group of the NCI’s Symptom/Quality of Life (SxQOL) Committee
Provided written responses to all inquiries 3

4. Process (con’d 2)
Developed interactive voice response (IVR) telephone platform with Perceptive Informatics (recall substudy)
Developed protocol document
Planned activation June 2010
Protocol modification underway to incorporate NCCCP sites
Participated in the development of an interactive voice response (IVR) telephone platform with Perceptive Informatics for the recall substudy
Selected items
Reviewed scripts & patient materials
Tested platform within the testing and live environments
Provided feedback on training materials for site staff 4

5. Objectives of Validation Study
To assess measurement properties of newly developed PRO-CTCAE items:
Validity
Reliability
Sensitivity
Recall period
N=900 to be accrued at 10 sites
Mayo, Memorial Sloan-Kettering, MD Anderson, Duke, Dana-Farber, 5 NCCCP Sites

6. Features of Validation Study
Rigorous assessment of measurement properties on an item-by-item basis
Follows FDA guidance document even though PRO-CTCAE items are intended for adverse event monitoring instead of as primary endpoints
Planned accrual of a diverse patient population
Six disease cohorts with a range of chemotherapies and/or radiation therapy
ECOG performance status 0-4
Targeting minority patients through NCCCP participation

7. Eligibility (Inclusions)
≥18 years of age
Disease and treatment matching 1 of the 6 following cohorts:
Adjuvant breast cancer on chemotherapy
Lymphoma/myeloma on chemotherapy
Metastatic prostate/bladder cancer on chemotherapy
Metastatic or locally advanced lung cancer on chemotherapy OR receiving daily radiation therapy for ≥21 more days (concurrent chemotherapy allowed)
Metastatic colorectal cancer on chemotherapy
Head/neck/gastroesophageal cancer receiving daily radiation therapy for ≥21 more days (concurrent chemotherapy allowed)
Patient is expected to return to clinic in 1-6 weeks
English speaking
NOTE: CAN BE ANY ECOG PS
We are particularly interested in accruing patients with ECOG PS 2-4!

8. Eligibility (Exclusion)
Clinically significant cognitive or memory impairment in the opinion of clinical or research staff

9. Schema Group A (N~100) Group B (N~100) Group C (N~700)
Patients receiving daily radiation for ≥21 more days in the Lung or Head/Neck/Gastroesophageal cohorts
Primary validation study plus recall and test-retest reliability substudies
Group B (N~100)
Patients with 4-5 planned weekly clinic visits
Primary validation study plus recall substudy
Group C (N~700)
All other eligible patients
Primary validation study (only requires two clinic visits 1-6 weeks apart)
Rationale: Keep the study simple for most patients (Group C) but target accrual of patients with more frequent clinic visits (Groups A & B) for the recall and test-retest reliability substudies

10. [ Patient compensation: $10 / visit ]
Schema (Group C)
[ Patient compensation: $10 / visit ]

11. * Clinical Anchors ECOG Performance Status
Patient treatment information
RT yes/no
Surgery yes/no
Chemotherapy yes/no + regimen
Patient medication information (yes/no for each)
Hormonal therapy
Opioid (narcotic) pain meds
Laxatives
Nausea meds
Sleep aids
Anti-diarrhea meds
Antacids
Anxiety meds
Inhalers
Depression meds.

12. Schema (Groups A & B) [ Patient compensation: $20 / visit ]

13. Statistics / Power
Primary: Assess convergent validity of each PRO-CTCAE item
Compare each item between patients with ECOG PS 0-1 vs 2-4 at the Visit 1 time point using t-tests
Adjust for multiplicity using Hochberg’s step-up method
Power
Core items: 99% for large effect size, 63-90% for moderate effect size
Non-core items: 48-99% for large effect size, 9-65% for moderate effect size

14. Other Planned Analyses
Assess the test-retest reliability of selected PRO-CTCAE items
Assess the responsiveness (sensitivity to change) and clinical significance of each PRO-CTCAE item
Investigate cut-points for notification of severe PRO-CTCAE symptoms

15. Other Planned Analyses (con’d)
Compare clinician- and patient-reported CTCAE items
Compare daily, 7-day, 2-week, 3-week, and 4-week recall periods
Explore construction of an overall grade for symptoms with multiple items
Assess measurement properties within ethnic/racial and education level subgroups

16. ASCO Poster Information
Title: Validation study of the patient-reported outcomes version of the common terminology criteria for adverse events (PRO-CTCAE)
Presenting author: Dueck AC
Session: Trials in Progress Poster Session
Date: Monday, June 07, 2010
Time: 8:00 AM - 12:00 PM
Presentation Order: 175
Poster Board #: 47E
Location: S Hall A2