Linking the European Organisation for Research and Treatment of Cancer Item Library to the Common Terminology Criteria for Adverse Events

Abstract

Purpose: The European Organisation for Research and Treatment of Cancer (EORTC) Item Library is an interactive online platform currently composed of 950 unique items (questions) derived from 67 patient-reported outcome (PRO) questionnaires. PROs complement clinician adverse event (AE) reporting classifications like the Common Terminology Criteria for Adverse Events (CTCAE). This work aims to create a standardized framework using the CTCAE to systematically classify symptomatic AEs from the EORTC Item Library through linking individual items to corresponding AEs.

Methods: The EORTC Item Library items were searched for within the CTCAE (v5.0) and linked to an AE if they were described within the AE's title, description, or grading. Symptoms described in EORTC items but not located in the CTCAE were coded as missing symptoms. Other nonsymptom EORTC items, not described within the CTCAE were assigned a non-CTCAE descriptive classification. Further descriptive codes (eg, multiple issues) were allocated to enable descriptive analysis. Two raters independently coded 26.2% (n = 249) of the items. The remaining 701 items were coded by one rater and verified by the second, followed by discussion with two additional raters to reach consensus.

Results: Overall, 625 (65.8%) EORTC items were linked to 208 different AEs. Three hundred sixty-nine items provide information about non-CTCAE cancer-related issues and were categorized into seven descriptive classifications, including body image; emotional impact of a symptom, diagnosis, or treatment; global health and quality of life; and impact on life and daily activities. Inter-rater agreement for independent coding was 79.1%. Bowel urgency and tenesmus were identified as missing symptoms in CTCAEv5.0.

Conclusion: The EORTC Item Library provides considerable coverage of CTCAE toxicities, along with other complementary issues important to patients with cancer. Using the CTCAE clinical framework to classify symptomatic PRO items may facilitate PRO selection and use in clinical trials and routine care.

FIG 1.

EORTC QLQ/CTCAE coding workflow. ^aItems coded as CTCAE SOC(s) and AE(s), missing symptom, or assigned a non-CTCAE classification. Description of process: phase I: two raters (A.G., UK English and C.P., North American English) independently coded 26.2% of the items from the Item Library taken from 19 questionnaires (26.2%; n = 249; QLQ-C30, BM22, BN20, BR23, CR29, CX24, EN24, GI.NET21, HCC18, H&N35, LC13, LMC21, MY20, OES18, OG25, OV28, PR25, PR23, and STO22). AE was defined as “any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure” as per the CTCAE (v5.0). If at least one common AE was selected by both raters or raters agreed that the item was not eligible for a CTCAE code, these were coded as agreement. Items for which there were any discrepancies (even those that had at least one overlapping AE) were discussed between both raters until an agreement was reached. Items where ambiguity remained were highlighted for later review. Phase II: the remaining 701 items were coded by one rater (C.P.) and then reviewed by the second (A.G.) to reach agreement, with ambiguous items highlighted for further review. Phase III: all 950 items were unblinded, revealing the source questionnaire, and reverified by both raters (A.G. and C.P.) to ensure that the primary coding accurately reflected the underlying issues for which the items were developed (on the basis of the scale structure[s] of their source questionnaires). A third rater was introduced (G.V.) to discuss the remaining ambiguous items to reach consensus. Phase IV: decisions about optimal higher-level coding choices (eg, coding of multiple AE for a single PRO item, and diagnostic AEs) were discussed between the two raters (A.G. and C.P.), and a fourth rater, M.G., was consulted to reach a final consensus. AE, adverse event; CTCAE, Common Terminology Criteria for Adverse Events; EORTC, European Organisation for Research and Treatment of Cancer; PRO, patient-reported outcome; QLQ, Quality of Life questionnaires; SOC, System Organ Class.