NCI Releases Updated Version of the Common Terminology Criteria for Adverse Events (CTCAE) Reporting in Clinical Trials

A healthcare professional compares physical and digital health records while taking notes on a tablet.

NCI recently released the sixth version of the CTCAE, which was developed through an inter-agency collaboration involving DCTD, NCI’s Division of Cancer Prevention, and FDA. Version 6.0 addresses several key challenges in adverse event (AE) reporting including:

Grading AEs in patients with abnormal baseline laboratory values
Characterizing AEs associated with immunotherapeutics
Refining the categorization of cardiac-related AEs

As with previous iterations of the CTCAE, extensive public comment from the global oncology community informed this version, and NCI staff considered all public feedback throughout the development process. For version control management, NCI has developed a comprehensive mapping resource that aligns all term and grade combinations from CTCAE v5.0 to those in CTCAE v6.0.

The History of AE Reporting

Prior to NCI’s development of the CTCAE, individual clinicians used their own terms and grading system for AEs. This made trial results difficult to compare and impacted the reproducibility of results. The lack of a shared language to report AEs in clinical trials delayed progress in cancer treatment.

First introduced in 1983 as the Common Toxicity Criteria (CTC), the CTCAE provides a universal standard for describing and grading AEs in cancer clinical trials. The CTCAE’s widespread adoption — by academic researchers, pharmaceutical partners, and regulatory agencies including the FDA — enables direct comparison of safety data across trials worldwide.

An Essential Tool for Clinical Trials

Today, the CTCAE remains one of the most important standardization tools in cancer research, which aims to:

Help protect patients
Improve the accuracy of AE reporting
Precisely determine the effects of new cancer treatment regimens

NCI also maintains the CTCAE to help define protocol parameters (such as maximum tolerated dose and dose-limiting toxicity) and to provide eligibility assessment and guidelines for dose modification. Physicians are required (according to Federal Regulation 21 CFR 312) to document and report AEs when signing the FDA 1572 Investigator Registration Form for clinical trials and are mandated to include the nature and severity of the AE in their clinical trial protocols. The CTCAE is essential to maintaining accuracy of these reporting requirements, ultimately helping to improve research standards and patient care.

Contact: Shanda Finnigan