receiving chemotherapy
Photo by Rhoda Baer
Results of a multicenter study indicate that a tool cancer patients can use to report adverse events (AEs) is as accurate as other, established patient-reported and clinical measures.
The tool is the National Cancer Institute’s Patient Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE).
Study investigators were able to validate 119 of 124 PRO-CTCAE questions against 2 established measurement tools.
The 5 questions that were not validated could not be evaluated due to underrepresentation in the study population.
This research was published in JAMA Oncology.
“In most cancer clinical trials, information on side effects is collected by providers who have limited time with their patients, and current patient questionnaires are limited in scope and depth,” said study author Amylou Dueck, PhD, of the Mayo Clinic in Scottsdale, Arizona.
“PRO-CTCAE is a library of items for patients to directly report on the level of each of their symptoms, to enhance the reporting of side effects in cancer clinical trials, which is normally based on information from providers. The study itself is unprecedented, as more than 100 distinct questions about symptomatic adverse events were validated simultaneously.”
To assess the PRO-CTCAE, Dr Dueck and her colleagues recruited 975 cancer patients from 9 clinical practices across the US, including 7 cancer centers.
The patients had a range of cancers and were undergoing outpatient chemotherapy and/or radiation therapy. The investigators said these participants reflected the geographic, ethnic, racial, and economic diversity in cancer clinical trials.
The patients were asked to fill out the PRO-CTCAE questionnaire before appointments. The investigators then compared patient reports to clinician-reported Eastern Cooperative Oncology Group (ECOG) performance status and the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (QLQ-C30).
A majority of patients completed items on the PRO-CTCAE questionnaire at their first visit (96.4%, 940/975) and second visit (90.6%, 852/940).
Most patients (99.8%, 938/940) reported having at least 1 symptomatic AE, with 81.7% (768/940) reporting at least 1 AE as frequent, severe, and/or interfering “quite a bit” with daily activities.
To gauge the accuracy of the PRO-CTCAE, the investigators assessed construct validity, test-retest reliability, and responsiveness of PRO-CTCAE items.
Construct validity
The investigators explained that construct validity reflects the association between a new measurement tool and an established measure.
Construct validity is often investigated through convergent validity, which determines whether the new tool moves in the same direction as an established instrument, and known-groups validity, which determines whether the tool can distinguish between groups of patients who are thought to be distinct.
When the investigators considered all QLQ-C30 functioning/global scales, they found that all 124 items on the PRO-CTCAE questionnaire were associated in the expected direction with 1 or more scales. One hundred and fourteen of the PRO-CTCAE items demonstrated a meaningful correlation (Pearson r≥0.1), and 111 of them were statistically significant (P<0.05 for all).
Scores for 94 of 124 PRO-CTCAE items were higher among patients with an ECOG performance status of 2 to 4 (17.1% of patients) than among patients with a score of 0 to 1. The difference was significant for 58 of the items (P<0.05 for all).
Test-retest reliability and responsiveness
The investigators said they estimated test-retest reliability using the intraclass correlation coefficient (ICC), based on a 1-way analysis of variance model with an ICC of 0.7 or greater interpreted as high.
Test-retest reliability was 0.7 or greater for 36 of 49 prespecified PRO-CTCAE items. The median ICC was 0.76 [range, 0.53-0.96).
The investigators assessed the responsiveness of PRO-CTCAE items by comparing any change from the first visit to the second visit in 27 items that were selected a priori.
Correlations between PRO-CTCAE item changes and corresponding QLQ-C30 scale changes were significant for all 27 items (P≤0.006 for all).
“This is a landmark study demonstrating that meaningful information about adverse events can be elicited from patients themselves, which is a major step for advancing the patient-centeredness of clinical trials,” said study author Ethan Basch, MD, of the Lineberger Cancer Center of the University of North Carolina in Chapel Hill.
