CTCAE (Common Terminology Criteria for Adverse Events)

The Common Terminology Criteria for Adverse Events (CTCAE) is the National Cancer Institute’s (NCI) standardized descriptive terminology and severity-grading system for adverse events observed in clinical trials. Developed and maintained by NCI’s Cancer Therapy Evaluation Program (CTEP), within the Division of Cancer Treatment and Diagnosis (DCTD), CTCAE originated in oncology trials but its grading logic — a common Grade 1 through Grade 5 severity scale applied consistently across hundreds of specific adverse-event terms — is now used well beyond oncology, in any trial that needs a reproducible way to say how severe an adverse event was, not just what it was.

What CTCAE Actually Standardizes

CTCAE does two things at once: it supplies a controlled list of specific adverse-event terms (organized by body system — e.g., specific terms for rash, neutropenia, diarrhea, elevated liver enzymes), and for each term it defines what distinguishes a mild instance of that event from a severe one, using a common five-point grade scale. An adverse event is “graded under CTCAE” when a study team selects the applicable CTCAE term and assigns it the grade whose published, term-specific criteria the observed event actually meets — not an ad hoc site-specific severity judgment, and not a grade assigned from memory of what a similar event looked like in a different trial. This is precisely the standardization problem CTCAE exists to solve: without a shared, term-specific grading definition, “severe nausea” means something different to every site coordinator and every sponsor reviewing pooled safety data across dozens of sites.

The CTCAE Grading Scale: Grade 1 Through Grade 5

Underneath every term-specific CTCAE grading table sits the same general severity framework, which CTEP’s own quick-reference materials define as follows:

• Grade 1 — Mild. Asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated.
• Grade 2 — Moderate. Minimal, local, or noninvasive intervention indicated; limits age-appropriate instrumental activities of daily living.
• Grade 3 — Severe or medically significant, but not immediately life-threatening. Hospitalization or prolongation of hospitalization indicated; disabling; limits self-care activities of daily living.
• Grade 4 — Life-threatening consequences. Urgent intervention indicated.
• Grade 5 — Death related to the adverse event.

Each specific CTCAE term (e.g., a particular laboratory abnormality or a named toxicity) then has its own worked-out version of this scale, sometimes anchored to a numeric lab threshold or a defined clinical intervention, published in the full CTCAE reference document for the version currently in use — a study team does not derive term-specific numeric thresholds itself. Not every term has a defined Grade 4 or Grade 5; some adverse events, by their nature, cannot reach those grades.

Current Version: CTCAE v6.0

CTEP released CTCAE v6.0 in 2025, superseding CTCAE v5.0 (published November 27, 2017), which itself had been the standing version for roughly eight years — a much longer gap than earlier revision cycles (v3.0 in 2003, v4.0 in 2009, v4.03 in 2010). Version 6.0 is the first CTCAE release distributed as a spreadsheet (Excel) file rather than only as a PDF, and the first to ship with a built-in crosswalk tab mapping every v5.0 term/grade combination to its v6.0 equivalent — a direct response to how disruptive a terminology change is for sites and sponsors mid-trial. Reported focus areas of the v6.0 revision include clearer grading criteria for adverse events in participants with abnormal baseline laboratory values, refined criteria for immunotherapy-associated adverse events, and reorganized cardiac- and skin-related term categories. A minor errata correction followed in January 2026.

For CTEP- and DCP-sponsored studies specifically, adoption of v6.0 was targeted for newly-opened studies as of January 1, 2026 — already-enrolling CTEP/DCP trials continue under the version specified in their protocol rather than switching mid-study. Trials outside the CTEP/DCP network are not bound by that timeline and may adopt v6.0 on their own schedule, which is why v5.0-graded data will remain in active use across the field for some time yet. A research administrator’s first practical question on any given trial is simply which CTCAE version the protocol specifies — that answer, not the newest release date, is what actually governs grading on that study.

CTCAE Grade Is Not the Same Question as SAE “Seriousness”

One of the most common points of confusion for research administrators new to safety reporting: a CTCAE grade measures severity; it is a separate question from whether an event is a serious adverse event (SAE). Under the ICH E2A definition used across expedited safety reporting, an event is “serious” if it results in death, is life-threatening, requires or prolongs inpatient hospitalization, causes persistent or significant disability, is a congenital anomaly, or is another medically important event requiring intervention to prevent one of those outcomes — a regulatory-reporting classification, not a severity scale. The two systems intersect but are not interchangeable: a Grade 2 (moderate) event can still meet SAE criteria if it triggers hospitalization, and conversely a high CTCAE grade does not, by itself, automatically make an event “serious” under ICH E2A unless it independently meets one of that definition’s specific criteria. CASRAI’s guide to pharmacovigilance in clinical research works through the full adverse event, SAE, and SUSAR reporting framework that CTCAE grading feeds into.

Why CTCAE Grading Matters for Research Administrators

CTCAE grading is not just a clinical documentation exercise — it is the common data language that lets adverse-event information move reliably between the parties who each need it for a different purpose:

• Sponsors pool CTCAE-graded events across every site in a multi-site trial to detect safety signals that would be invisible in any single site’s data, and use grade distributions to support periodic and expedited regulatory safety reports.
• Institutional Review Boards (IRBs) use CTCAE grade, alongside SAE/causality determinations, during continuing review to assess whether a trial’s risk profile still matches what participants originally consented to.
• Data Safety Monitoring Boards (DSMBs) — the independent bodies covered in CASRAI’s Data Safety Monitoring Board (DSMB) entry — receive CTCAE-graded, typically unblinded, by-arm adverse-event data at each scheduled review as core input to their stop/continue/modify recommendation; a DSMB reviewing raw, ungraded event narratives instead of standardized CTCAE grades could not meaningfully compare event severity across a trial’s arms.

Because all three of those downstream uses depend on grading being applied consistently, a research administrator’s practical responsibilities are less about assigning grades directly (typically a clinical/investigator judgment) and more about protocol- and system-level discipline: confirming which CTCAE version the protocol specifies, ensuring site staff and the clinical trial management system are configured to that version’s term list, and flagging a version mismatch between sites in a multi-site study before it corrupts pooled safety data.

Frequently Asked Questions

Is CTCAE only used in oncology trials?

No. CTCAE originated in, and remains most closely associated with, oncology trials — where NCI/CTEP sponsorship made it the default standard — but its grading framework is now widely adopted in non-oncology trials as a general-purpose adverse-event severity scale, particularly where a sponsor wants comparability with the broader body of CTCAE-graded trial data.

Who assigns the CTCAE grade for an adverse event?

Grading is a clinical judgment made by the investigator or delegated clinically-qualified study staff, applying the term-specific CTCAE criteria for the version specified in the protocol — not an administrative or purely data-entry function, even though the resulting grade is what flows into administrative reporting systems.

What happens if a trial switches CTCAE versions mid-study?

Sponsors generally avoid switching versions mid-trial precisely because grade definitions for a given term can change between versions, which would make earlier and later safety data non-comparable; this is why CTCAE v6.0’s built-in crosswalk to v5.0 term/grade combinations is a meaningful feature rather than a cosmetic one, and why CTEP/DCP-sponsored trials already open before the v6.0 transition date continue under their original version rather than switching.

Does a higher CTCAE grade automatically mean an event must be reported as an SAE?

No. CTCAE grade and SAE “seriousness” are determined against two different definitions (see above) and are reported alongside each other, not derived from each other — an event can be low-grade and still serious, or comparatively high-grade and not meet the regulatory seriousness criteria.