Background

Safety and tolerability are fundamental to conclusions about the effectiveness of cancer therapies, including comparative effectiveness. The standard lexicon for reporting adverse events (AEs) in NCI-sponsored clinical trials is the Common Terminology Criteria for Adverse Events (CTCAE), now in version 5. 10% of the more than 800 adverse events listed in the CTCAE are symptoms, and thus are amenable to self-reporting. There is evidence that the validity of symptom reports may be eroded when filtered through clinicians and other research staff. Moreover, staff-based AE reporting occurs at clinic visits, and thus AEs occurring between visits may be missed. Real-time ascertainment of symptomatic adverse events using patient-reported outcomes (PROs) can improve the precision and reproducibility of adverse event reporting.

Developed to complement standard toxicity reporting using the CTCAE, the US National Cancer Institute's PRO-CTCAE Measurement System allows patient self-reporting of the frequency, severity, interference or presence/absence of symptomatic adverse events.

The PRO-CTCAE Item Library (PDF, 124 KB) allows for self-reporting by patients older than age 17, and includes 124 items representing 78 symptomatic toxicities. The PRO-CTCAE Item Library has been linguistically validated in more than 30 languages.

The pediatric module includes 130 items representing 62 symptomatic toxicities, and permits self-reporting by children and adolescents ages 7-17 years (Ped-PRO-CTCAE® (PDF, 174 KB)) or caregiver-reporting for children ages 7-17 who are unable to self-report (Ped-PRO-CTCAE®[Caregiver] (PDF, 174 KB)). Ped-PRO-CTCAE and Ped-PRO-CTCAE [Caregiver] were validated in the US and are currently available in English. Ped-PRO-CTCAE module has been linguistically validated in Italian and Simplified Chinese, and several other languages are in development.

Capturing symptomatic toxicity can be challenging since the onset and character of adverse events varies within and across trials based on the distinct, on- and off-target toxicity profile of a specific therapy or regimen. Thus, the approach to measuring symptomatic toxicity must be flexible within and across studies.

The National Cancer Institute's PRO-CTCAE Measurement System was developed as a companion to the CTCAE and offers a systematic yet flexible approach to capture symptomatic adverse events in trials of new cancer therapies. PRO-CTCAE permits self-reporting by individuals across the developmental spectrum and accommodates diverse linguistic preferences. It is not intended to be used as a stand-alone patient-reported outcome (PRO), or to be included in every trial.

The current standard for grading and reporting all adverse events (AEs) in cancer clinical trials, including symptomatic AEs, is clinician grading using the CTCAE. At the same time, data captured using the PRO-CTCAE Measurement System can provide information about symptomatic adverse events during and following cancer treatment that is valuable to patients, their clinicians, trial sponsors, and regulators. It may also contribute to determinations of benefit and harm at the study level and improve our overall understanding of treatment tolerability.