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

Validation Study of the Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-

CTCAE)

• 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

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

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

• To assess measurement properties of newly developed PRO-CTCAE items:

ValidityReliabilitySensitivity

Recall period

• N=900 to be accrued at 10 sites–Mayo, Memorial Sloan-Kettering, MD Anderson, Duke,

Dana-Farber, 5 NCCCP Sites

Objectives of Validation Study

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)

– 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

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