Validity and Reliability of the U.S. National Cancer Institute's Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE)

Abstract

Importance

Symptomatic adverse events (AEs) in cancer trials are currently reported by clinicians using the National Cancer Institute's (NCI) Common Terminology Criteria for Adverse Events (CTCAE). To integrate the patient perspective, the NCI developed a patient-reported outcomes version of the CTCAE (PRO-CTCAE) to capture symptomatic AEs directly from patients.

Objective

To assess the construct validity, test-retest reliability, and responsiveness of PRO-CTCAE items.

Design

Participants completed PRO-CTCAE items on tablet computers in clinic waiting rooms at two visits 1-6 weeks apart. A subset completed PRO-CTCAE items during an additional visit one business day after the first visit.

Setting

Nine U.S. cancer centers and community oncology practices.

Participants

975 adult cancer patients undergoing outpatient chemotherapy and/or radiation enrolled between January 2011 and February 2012. Eligibility required participants to read English and be without clinically significant cognitive impairment.

Main Outcome(s) and Measure(s)

Primary comparators were clinician-reported Eastern Cooperative Oncology Group Performance Status (ECOG PS) and the European Organisation for Research and Treatment of Cancer Core Quality of Life Questionnaire (QLQ-C30).

Results

940/975 (96%) and 852/940 (91%) participants completed PRO-CTCAE items at each visit. 938/940 (99.8%) participants (53% female, median age 59, 32% high school education or less, 17% ECOG PS 2-4) reported having at least one symptom. All PRO-CTCAE items had at least one correlation in the expected direction with a QLQ-C30 scale (111/124 P<.05). Stronger correlations were seen between PRO-CTCAE items and conceptually-related QLQ-C30 domains. Scores for 94/124 PRO-CTCAE items were higher in the ECOG PS 2-4 versus 0-1 group (58/124 P<.05). Overall, 119/124 items met at least one construct validity criterion. Test-retest reliability was acceptable for 36/49 pre-specified items (median intra-class correlation coefficient .76; range .53-.96). Correlations between PRO-CTCAE item changes and corresponding QLQ-C30 scale changes reached statistical significance for 27 pre-specified items (median r=.43, range .10-.56; all P≤.006).

Conclusions and Relevance

Evidence demonstrates favorable validity, reliability, and responsiveness of PRO-CTCAE in a large, heterogeneous U.S. sample of patients undergoing cancer treatment. Studies evaluating other measurement properties of PRO-CTCAE are underway to inform further development of PRO-CTCAE and its inclusion in cancer trials.