CTCAE v6.0 migration guide, part 1: what changed and how to plan for it

CTCAE v6.0 was published by the National Cancer Institute on July 22, 2025 under MedDRA 28.0. It keeps the 26 organ system classes of v5.0, which had 837 terms. CTCAE v6.0 has 850 terms: 45 new, 7 renamed, and 376 reworded at one grade or more since v5.0. A CTCAE v6 migration is a retraining and data-management exercise rather than a new grading framework: the grade scale stays the same, and specific cutoffs and terms move.

Look up any term in both versions at ctcae.ai/v6-changes. Every rename, every new term and every term only v5.0 carries, side by side and grade by grade.

Part 1 of the Burna AI CTCAE v6.0 migration guide, for research coordinators, oncology research nurses and research operations leads: what changed, what did not, and how to plan the move.

CTCAE v6.0 at a glance

NCI's adverse events page describes v6.0 as the current version of the Common Terminology Criteria for Adverse Events, released in 2025, and lists v5.0 as the 2017 publication under MedDRA 20.1 (NCI CTEP, adverse events).

	CTCAE v5.0	CTCAE v6.0
Published	November 27, 2017	July 22, 2025
MedDRA version	20.1	28.0
Terms	837	850
Organ system classes	26	26
Grades	1 to 5	1 to 5

Comparing the two vocabularies term by term gives the full delta:

• 790 terms keep their name. 376 of those read differently at one grade or more. Sometimes the difference is only notation; sometimes it moves a grade.
• 7 terms were renamed, each with a new MedDRA code.
• 8 v6.0 terms are one-directional substitutions: they have no v5.0 equivalent, so a v5.0 protocol records a mapped v5.0 term instead.
• 45 terms are new in v6.0.
• 40 terms exist only in v5.0.

NCI names three areas v6.0 addresses: grading adverse events in patients with abnormal baseline laboratory values, characterizing adverse events associated with immunotherapeutics, and refining the categorization of cardiac-related adverse events (NCI announcement).

What changed from CTCAE v5 to v6

The changes fall into five kinds.

1. Count cutoffs that moved a grade

The blood counts carry the changes most likely to alter a grade in daily work.

• Neutrophil count decreased moved every band. In v6.0, grade 1 starts below 1,500/mm3 and grade 4 starts below 100/mm3, where v5.0's grade 4 started below 500/mm3. ("Neutropenia" is not a CTCAE term in either version; the term is Neutrophil count decreased, with Febrile neutropenia graded separately.)
• Thrombocytopenia replaces Platelet count decreased. Grades 1 and 2 are unchanged, grade 3 now runs from 50,000 down to 10,000/mm3 with transfusion indicated, and grade 4 is below 10,000/mm3 with life-threatening consequences. In v5.0, grade 4 began below 25,000/mm3.
• Lymphopenia replaces Lymphocyte count decreased, and v6.0 grades it only as grade 1, "Present". v5.0 graded the count across grades 1 to 4.
• Anemia differs only in notation. The grades are the same.

The same number can now land on a different grade:

Count	v5.0 grade	v6.0 grade
ANC of 800/mm3	Grade 3	Grade 2
Platelets of 18,000/mm3	Grade 4 (Platelet count decreased)	Grade 3 (Thrombocytopenia)

2. Liver labs when the baseline was already abnormal

For Alanine aminotransferase increased and Blood bilirubin increased, v6.0 rewrote the path for a patient whose baseline was already above the upper limit of normal, and grades it against tighter multiples of that baseline. For ALT, grade 1 on an elevated baseline is 1.0 to 1.5 times baseline in v6.0, where v5.0's abnormal-baseline grade 1 began at 1.5 times baseline. This is the abnormal-baseline focus NCI names, and it matters for patients who start a trial with elevated liver tests.

3. Symptom criteria and the pediatric wording

v6.0 adds pediatric wording to the general definitions of grades 2 and 3, alongside the instrumental and self-care ADL language, and many symptom terms carry it. Some symptom criteria changed in substance:

• Diarrhea: grade 1 becomes "Change in consistency or frequency", and grade 3 adds "requires IV intervention".
• Nausea: grade 2 adds "IV intervention indicated".
• Peripheral sensory neuropathy: grade 1 changes from "Asymptomatic" to "Mild symptoms".
• Fatigue: the adult criteria are unchanged; v6.0 adds the pediatric wording at grades 2 and 3.

4. Immunotherapy and cellular therapy events

v6.0 adds terms with no v5.0 counterpart, among them Immune effector cell-associated neurotoxicity syndrome, Tumor inflammation-associated neurotoxicity and Secondary hemophagocytic lymphohistiocytosis. Cytokine release syndrome now defines hypoxia by the oxygen delivery device rather than by the fraction of oxygen: grade 2 is hypoxia requiring low-flow nasal cannula or blow-by, and grade 3 is hypoxia requiring high-flow nasal cannula, facemask, nonrebreather mask or Venturi mask. v5.0 drew the line between those two grades at 40 percent oxygen.

5. Renamed terms, cardiac terms and terms one version lacks

The seven renames are the same event under a new name and a new MedDRA code. Lists, forms and coding conventions that still carry the v5.0 name are where a migration breaks first.

v5.0 term	v6.0 term
Platelet count decreased	Thrombocytopenia
Lymphocyte count decreased	Lymphopenia
Thromboembolic event	Venous thromboembolism
Lung infection	Pneumonia
Edema limbs	Peripheral edema
Thrush	Candidiasis
Proteinuria	Urinary protein increased

Cardiac disorders went from 34 terms to 30. Ejection fraction decreased and Left ventricular systolic dysfunction exist only in v5.0, and v6.0's Left ventricular dysfunction is one of the one-directional substitutions: a v5.0 protocol records it as Ejection fraction decreased at grade 2, or Left ventricular systolic dysfunction at grade 3 or higher. Another substitution is Diabetes mellitus, which a v5.0 protocol records as Hyperglycemia. Substitutions run in that direction only.

What did not change between v5.0 and v6.0

• The grade scale. Grades still run from 1 to 5 with the same general meaning: grade 1 mild, grade 4 life-threatening, grade 5 death related to the adverse event. v6.0 states explicitly that a grade is assigned when a finding meets any of the conditions separated by a semicolon. CTCAE grades 1 to 5, explained for research coordinators walks through each grade.
• Severity is not seriousness or attribution. CTCAE grades how severe an event is. Whether it is serious follows the ICH E2A criteria, and whether the study drug caused it is a separate attribution judgment. v6.0 changes neither.
• Every term is a MedDRA Lowest Level Term. Each v6.0 term is a MedDRA 28.0 LLT. No term that kept its name changed its LLT code; the renamed terms carry new codes, such as Platelet count decreased (10035528) becoming Thrombocytopenia (10043554).

The framework is the same. What a site retrains on is the specific criteria inside it.

When can a trial start using CTCAE v6.0?

Most studies can use CTCAE v6.0 now. NCI CTEP and DCP studies already open on v5.0 stay on v5.0 for the life of the study, and any one study grades on the version its protocol names. NCI's CTCAE v6.0 implementation FAQ, dated September 9, 2025, sets out the general position:

• Most studies can use v6.0 now. NCI describes v6.0 as ready for immediate use for any study except NCI CTEP or DCP NCORP studies, and sends questions about a specific study to its sponsor.
• NCI CTEP and DCP studies already on v5.0 stay on v5.0. They keep reporting in v5.0 for the life of the study, and NCI does not require their data to be converted.
• New NCI CTEP and DCP studies move to v6.0. v6.0 is required for every new CTEP and DCP study whose Rave study build begins after the CTCAE v6.0 Rave ALS (ALS 7.2) is released.
• v6.0 is the latest version, and it is final. NCI plans no further changes to v6.0 and expects CTCAE v7.0 to be developed and released between 2027 and 2030.
• NCI maps v5.0 to v6.0 for consolidation. Where data must be combined into one version, for regulatory reporting or an aggregate analysis, NCI's mapping resource aligns every v5.0 term and grade combination with its v6.0 counterpart.

A site or sponsor with studies already open on v5.0 therefore runs both versions side by side until those studies close.

How to plan a CTCAE v6 migration

1. Confirm the version each protocol names. Record the version on every grade, so v5.0 and v6.0 grades never mix in one dataset.
2. Retrain on the changes that move a grade. Start with the terms your trials grade most often: the blood counts, abnormal-baseline liver labs, cytokine release syndrome and neurotoxicity for cellular therapy trials, and the gastrointestinal symptoms. Terms whose difference is notation only, such as Anemia, need no retraining.
3. Update every list that names a term. EDC pick lists, case report forms, source worksheets, SOPs and any grading tool that holds criteria text. Renamed terms and v5.0-only terms are where stale lists fail. NCI's v6.0 Excel file includes a tracked changes document and a mapping to v5.0 (NCI CTEP, adverse events).
4. Check coding and reconciliation. v6.0 terms are MedDRA 28.0 LLTs, and the seven renames change codes. Safety database coding conventions, reconciliation rules and pooled analyses need to know which version each record was graded under.
5. Keep a lookup open during real grading. A coordinator who knew the v5.0 criteria by heart now checks each one against v6.0. Every CTCAE v6.0 change, term by term, is free at ctcae.ai.

Part 2 of this guide covers running CTCAE v5.0 and v6.0 through the transition: how sponsors and sites keep both versions comparable across a portfolio.

How Burna AI handles both versions

Burna AI grades every encounter in CTCAE v5 and v6 with the criterion attached. Each trial records the CTCAE publication it grades against, every grade carries its version, and every grade traces to the line in the medical record that produced it. Which CTCAE versions Burna AI supports has the detail. AI suggests, clinicians decide.

To see both versions graded on your own trials, book a 15-minute conversation.

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Part 1 of the Burna AI CTCAE v6.0 migration guide.

About Burna AI: The AI platform for accelerated clinical research, from first-in-human trials through postmarket surveillance. Burna AI performs automated adverse event grading and attribution in real time, providing clear rationale and audit-ready evidence, including generation of IRB, sponsor and FDA reports. Burna AI delivers CTCAE v5 and v6 grades and MedDRA LLT codes on every encounter; enabling standardization, cross-site consistency and accuracy of clinical research data. AI suggests, clinicians decide. Human-in-the-loop, always.