CTCAE v6.0 in Cooperative Group and NCI-Sponsored Trials

Cooperative groups and NCI-sponsored programs play an outsized role in defining how CTCAE versions are used in practice. CTCAE v6.0 is now the designated successor to v5.0, but its rollout in the NCI ecosystem is carefully staged to protect data integrity and trial continuity.

The NCI Context: CTCAE as a Core Infrastructure

The Cancer Therapy Evaluation Program (CTEP) and Division of Cancer Prevention (DCP) have long relied on CTCAE as the standard tool for AE grading in NCI-sponsored trials. CTCAE feeds into:

• Protocol templates and standard language

• Rave-based electronic data capture systems

• CTEP-AERS and other adverse event reporting tools

• Education materials for investigators and research staff

When CTCAE moves from v5.0 to v6.0, all of these layers must move in step.

Official NCI Position on CTCAE v6.0

NCI's guidance on CTCAE v6.0 establishes two key principles:

• Existing CTEP/DCP studies using v5.0 will remain on v5.0 for their entire lifecycle. There is no expectation to convert historical AE data to v6.0 mid-trial.

• New NCI-sponsored trials will adopt v6.0 once associated systems (including Rave ALS 7.2 builds) are ready, targeting implementation around 2026.

This dual-version environment ensures continuity for ongoing studies while enabling modernized grading in future protocols.

What Cooperative Groups Need to Do

Groups such as SWOG, Alliance, ECOG-ACRIN, and others must operationalize NCI policy across many trials and sites. Practical steps include:

• Updating group protocol templates to specify CTCAE v6.0 for trials activated after the NCI implementation date.

• Revising AE sections in existing templates to reflect v6.0 terminology and definitions.

• Providing harmonized training slide decks and webinars that highlight the most impactful changes in v6.0.

SWOG, for example, has already produced educational slide sets titled "What's new in CTCAE v6," which walk investigators and coordinators through key updates.

Impact on Rave and Adverse Event Reporting

Most NCI-sponsored trials use standardized Rave builds. For CTCAE v6.0:

• New Rave libraries (such as ALS 7.2) incorporate updated CTCAE terms, codes, and help text.

• AE forms and lab modules are synchronized with v6.0 definitions, especially for hematologic and lab-based toxicities.

• Downstream systems like CTEP-AERS are configured to accept and interpret v6.0 grading consistently.

For cooperative groups, this means:

• Coordinating go-live dates for v6.0-based builds with NCI

• Ensuring that legacy v5.0 trials continue to use their original forms without mid-stream edits

• Communicating clearly with sites during transitions, so there is no confusion over which version applies to which trial

Training Investigators and Site Teams

Because NCI trials often involve broad site networks, training is critical.

Effective strategies include:

• Central webinars with case-based v6.0 grading examples, recorded for on-demand viewing

• Group-specific quick-reference guides summarizing hematologic changes, lab thresholds, and frequently encountered symptom AEs.

• Integration of v6.0 content into mandatory investigator meetings and site initiation visits.

Training should emphasize that:

• v5.0 and v6.0 grading are not interchangeable

• Investigators must know which version is specified in each protocol

• AE queries may increase temporarily as teams adapt to v6.0 definitions

Handling Publications and Cross-Trial Comparisons

Cooperative groups routinely publish cross-protocol analyses and meta-analyses. With mixed CTCAE versions, several rules of good practice apply:

• Always state which CTCAE version was used in each trial.

• When comparing trials across versions, describe how grading differences (for example, neutropenia shifts) might influence observed rates of Grade 3–4 events.

• Consider using NCI's v5.0–v6.0 mapping resources when pooled analyses are necessary, and document any mapping assumptions.

Transparency around CTCAE versioning will be essential for readers, guideline panels, and regulators interpreting cooperative group data.

The Role of PRO-CTCAE in NCI and Group Trials

NCI's PRO-CTCAE initiative has strong roots in cooperative group settings, where patient-reported toxicity is increasingly embedded into trial designs. As v6.0 becomes standard, cooperative groups can:

• Align clinician CTCAE v6.0 grading with PRO-CTCAE items in trial designs and analysis plans.

• Use PRO data to validate grading consistency and highlight under-recognized symptomatic toxicities.

This integration strengthens the evidentiary value of NCI-sponsored trials for patient-centered care.

CTCAE v6.0 will define the next generation of NCI and cooperative group research. Groups that invest early in implementation, training, and transparent reporting will help set the standard for how toxicity is captured and understood in modern oncology