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

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”

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

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

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

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

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!

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

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

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

* 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.

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

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

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

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

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