The PRO-CTCAE Measurement System

The NCI Patient Reported Outcomes-Common Terminology Criteria for Adverse Events (PRO-CTCAE) is a new patient-reported outcome measurement system developed to characterize the frequency, severity and interference of 78 symptomatic treatment toxicities. These include symptomatic toxicities such as pain, fatigue, nausea, and cutaneous side effects such as rash and hand-foot syndrome, all toxicities that can be meaningfully reported from the patient perspective.

The PRO-CTCAE measurement system consists of an item library of adverse symptoms, and a prototype electronic platform with a variety of features designed to promote integration of the PRO-CTCAE measurement system into clinical trials workflow. The system allows for data collection via the web, a hand-held computer, or an interactive voice-response system, and includes features that allow for customized PRO-CTCAE questionnaires, tailoring the schedule for data collection, as well as patient reminders and clinician alerts for severe symptoms.

Development and validation of PRO-CTCAE were consistent with well-established measurement principles as well as guidelines for patient-reported outcomes instrument development proposed by the US Food and Drug Administration (FDA) and European Medicines Agency (EMA). The development process included patients with cancer as well as professionals from the US and Europe with expertise in oncology, instrument development, clinical research and the regulatory aspects of cancer therapy development.

Each of the 78 symptom terms included in the PRO-CTCAE item library (PDF, 179 KB) is assessed relative to one or more distinct attributes, including presence/absence, frequency, severity, and/or interference with usual or daily activities. Responses are provided on a 5-point Likert scale. The standard PRO-CTCAE recall period is "the past 7 days."

PRO-CTCAE items were created with substantial input from patients, clinicians and PRO methodologists, and underwent refinement through cognitive interviews with patients to establish content validity in both English and Spanish. Subsequently, the quantitative measurement properties, including validity, reliability and responsiveness were evaluated in a large and diverse sample of patients receiving cancer treatment at one of six sites around the US. This large-scale multicenter validation study in individuals receiving active cancer therapy provides evidence for the validity, reliability, and responsiveness of the items that make up the PRO-CTCAE item library.

Administration of PRO-CTCAE via different modes, including screen-based, interactive voice response, and paper, offers flexibility for patients and for study operations personnel, and there is psychometric evidence to justify comparison of results and pooled analyses across studies that employ different PRO-CTCAE modes of administration.

PRO-CTCAE is intended to enhance the quality of adverse event data reporting in clinical trials, provide data that complements and extends the information provided by clinician reporting using CTCAE, represent the patient perspective of the experience of symptomatic adverse events, and improve detection of potentially serious adverse events.