Feasibility of Patient Reporting of Symptomatic Adverse Events via the Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) in a Chemoradiotherapy Cooperative Group Multicenter Clinical Trial

Purpose

To assess the feasibility of measuring symptomatic adverse events (AEs) in a multicenter clinical trial using the National Cancer Institute's Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE).

Methods and Materials

Patients enrolled in NRG Oncology's RTOG 1012 (Prophylactic Manuka Honey for Reduction of Chemoradiation Induced Esophagitis-Related Pain during Treatment of Lung Cancer) were asked to self-report 53 PRO-CTCAE items representing 30 symptomatic AEs at 6 time points (baseline; weekly ×4 during treatment; 12 weeks after treatment). Reporting was conducted via wireless tablet computers in clinic waiting areas. Compliance was defined as the proportion of visits when an expected PRO-CTCAE assessment was completed.

Results

Among 226 study sites participating in RTOG 1012, 100% completed 35-minute PRO-CTCAE training for clinical research associates (CRAs); 80 sites enrolled patients, of which 34 (43%) required tablet computers to be provided. All 152 patients in RTOG 1012 agreed to self-report using the PRO-CTCAE (median age 66 years; 47% female; 84% white). Median time for CRAs to learn the system was 60 minutes (range, 30-240 minutes), and median time for CRAs to teach a patient to self-report was 10 minutes (range, 2-60 minutes). Compliance was high, particularly during active treatment, when patients self-reported at 86% of expected time points, although compliance was lower after treatment (72%). Common reasons for noncompliance were institutional errors, such as forgetting to provide computers to participants; patients missing clinic visits; Internet connectivity; and patients feeling “too sick.”

Conclusions

Most patients enrolled in a multicenter chemoradiotherapy trial were willing and able to self-report symptomatic AEs at visits using tablet computers. Minimal effort was required by local site staff to support this system. The observed causes of missing data may be obviated by allowing patients to self-report electronically between visits, and by using central compliance monitoring. These approaches are being incorporated into ongoing studies.

Introduction

Adverse events (AEs) are reported in cancer clinical trials using the US National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) (1). The CTCAE is a library of items representing 790 discrete AEs. Each AE is graded using a 5-point numerical scoring system, which is anchored to discrete clinical criteria (2). Approximately 10% of AEs in the CTCAE are symptoms (eg, nausea, sensory neuropathy) that in trials have historically been reported by clinical investigators (3). However, there is empiric evidence that collection of this information directly from patients improves the reliability and precision of symptomatic AE detection in trials 4, 5, 6, 7.

Recently, the NCI developed a library of patient-reported outcome (PRO) items to supplement the CTCAE, called the PRO-CTCAE (8). The PRO-CTCAE was developed by systematically identifying AEs in the CTCAE that are amenable to patient self-report, then creating PRO items for each of these using rigorous interdisciplinary methods (9), then by establishing the measurement properties of these items using qualitative (10) and quantitative (11) psychometric methods.

For each AE in the PRO-CTCAE, between 1 and 3 items are included to assess the frequency, severity, and/or interference with activities related to that AE (Table E1; available online at www.redjournal.org). The PRO-CTCAE can be administered to patients electronically using software hosted at the NCI, which has undergone usability testing and refinement (9).

Although it is established that PRO-CTCAE items are well understood by patients and accurately represent symptomatic AEs, the feasibility of implementation of PRO-CTCAE items in multicenter cancer clinical trials is not established. Specifically, the level of staff effort required to teach and remind patients to self-report using the PRO-CTCAE software and to manage these data, staff acceptance, and patient willingness and ability to longitudinally self-report during treatment are unknown. This information is essential for determining whether it is practical to use the PRO-CTCAE in future trials, and for providing information about barriers and strategies toward more broadly integrating the PRO-CTCAE into clinical trial workflow.