Amylou C. Dueck (Mayo Clinic) – Task 7 Lead

1. Validation Study of the Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) AmylouC. 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 • https://wiki.nci.nih.gov/x/cKul • 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

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

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

11. 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. * Clinical Anchors

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