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

Abstract

Importance: To integrate the patient perspective into adverse event reporting, the National Cancer Institute developed a patient-reported outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE).

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

Design, setting, and participants: A total of 975 adults with cancer undergoing outpatient chemotherapy and/or radiation therapy enrolled in this questionnaire-based study between January 2011 and February 2012. Eligible participants could read English and had no clinically significant cognitive impairment. They completed PRO-CTCAE items on tablet computers in clinic waiting rooms at 9 US cancer centers and community oncology practices at 2 visits 1 to 6 weeks apart. A subset completed PRO-CTCAE items during an additional visit 1 business day after the first visit.

Main outcomes and measures: 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: A total of 940 of 975 (96.4%) and 852 of 940 (90.6%) participants completed PRO-CTCAE items at visits 1 and 2, respectively. At least 1 symptom was reported by 938 of 940 (99.8%) participants. Participants' median age was 59 years; 57.3% were female, 32.4% had a high school education or less, and 17.1% had an ECOG PS of 2 to 4. All PRO-CTCAE items had at least 1 correlation in the expected direction with a QLQ-C30 scale (111 of 124, P<.05 for all). Stronger correlations were seen between PRO-CTCAE items and conceptually related QLQ-C30 domains. Scores for 94 of 124 PRO-CTCAE items were higher in the ECOG PS 2 to 4 vs 0 to 1 group (58 of 124, P<.05 for all). Overall, 119 of 124 items met at least 1 construct validity criterion. Test-retest reliability was 0.7 or greater for 36 of 49 prespecified items (median [range] intraclass correlation coefficient, 0.76 [0.53-.96]). Correlations between PRO-CTCAE item changes and corresponding QLQ-C30 scale changes were statistically significant for 27 prespecified items (median [range] r=0.43 [0.10-.56]; all P≤.006).

Conclusions and relevance: Evidence demonstrates favorable validity, reliability, and responsiveness of PRO-CTCAE in a large, heterogeneous US sample of patients undergoing cancer treatment. Studies evaluating other measurement properties of PRO-CTCAE are under way to inform further development of PRO-CTCAE and its inclusion in cancer trials.

Figure 1. Pearson Correlations between 124 PRO-CTCAE Item Scores and EORTC QLQ-C30 HRQOL Summary Score* at Visit 1

Abbreviations: PRO-CTCAE, Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events; EORTC QLQ-C30, European Organisation for Research and Treatment of Cancer Core Quality of Life Questionnaire; HRQOL, Health-related quality of life; CTCAE, Common Terminology Criteria for Adverse Events *See eTable 3 for all computed Pearson correlations between PRO-CTCAE items and EORTC QLQ-C30 functioning, global, and symptom scales.

Figure 1. Pearson Correlations between 124 PRO-CTCAE Item Scores and EORTC QLQ-C30 HRQOL Summary Score* at Visit 1

Abbreviations: PRO-CTCAE, Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events; EORTC QLQ-C30, European Organisation for Research and Treatment of Cancer Core Quality of Life Questionnaire; HRQOL, Health-related quality of life; CTCAE, Common Terminology Criteria for Adverse Events *See eTable 3 for all computed Pearson correlations between PRO-CTCAE items and EORTC QLQ-C30 functioning, global, and symptom scales.

Figure 2. Standardized Response Means across 27 PRO-CTCAE Items by Patient-Reported Global Impression of Change Category*

Abbreviation: PRO-CTCAE, Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events *Figure 2 includes 27 frequency, severity, and interference items selected prior to initiation of the responsiveness analysis. The set of 20 “core” symptomatic AEs was reviewed and symptomatic AEs were selected if they had high potential to be meaningfully related to global changes in quality of life, physical condition, and/or emotional state (i.e., the Global Impression of Change items which were administered at the second visit). Of the 20 reviewed symptomatic AEs, 13 were included based on this criterion (see eTable 2). The symptomatic AEs which were excluded were felt to be related to initiation or changes in specific treatments (dry mouth, problems with tasting food/drink, rash) so may not exhibit change in a heterogeneously treated sample of patients; require a longer duration of follow-up to exhibit change (arm/leg swelling, hair loss); or be related to cognitive condition (headache, problems with concentration) which was not assessed in the Global Impression of Change items.