CTCAE grading remains one of the most important standards in oncology, it shapes patient safety decisions, trial integrity, and the credibility of outcomes that influence approvals. Yet even in 2025, accurate grading is still harder than it should be. The gap is not about whether clinicians value CTCAE, it is about the realities of time, fragmented data, and the complexity of translating narrative care into standardized grades.

This is a moment of operational truth. We have more digital infrastructure and more AI capability than ever, but CTCAE reliability still depends on human interpretation under pressure. The right path forward is not replacing clinicians. It is strengthening the system around them.

What works today

Shared training and calibration

Sites that invest in ongoing calibration, not just one-time onboarding, tend to show better consistency. Regular review of tricky cases builds a shared mental model and reduces drift over time.

Targeted review for high-risk events

Focused oversight of Grade 3+ risk patterns, early-cycle windows, or known toxicity profiles often produces better outcomes than trying to review everything equally.

Structured documentation habits

Simple prompts that encourage clinicians to capture onset, duration, functional impact, and relevant labs can materially improve grading quality. This is a low-tech lever that still matters.

What still fails, and why

The narrative-to-grade bottleneck

CTCAE is standardized, real-world documentation is not. Symptoms are described differently across clinicians and settings, and the same clinical reality can be captured with widely different language. That variability is hard to compress into a consistent grade without support.

Inter-rater variability remains inevitable in edge cases

Even experienced oncologists may grade the same scenario differently when attribution, baseline status, and functional impact are ambiguous. This is not a competence issue. It is the natural consequence of complex judgment applied without consistent scaffolding.

Timing and context gaps

Adverse events change between visits. Lab-based events can be particularly tricky when labs are drawn outside neat windows or when narrative context is incomplete. These issues quietly introduce inconsistency across sites.

Trial versus routine-care friction

Trials demand specificity and auditability. Routine care prioritizes speed and clinical pragmatism. Asking the same documentation flow to excel at both, without added structure, creates persistent gaps.

Burden creates risk

Manual AE identification, grading, and entry are time heavy. When workload rises, omissions and delays become more likely. That burden is not just an efficiency story, it is a safety and data-quality story.

What's next, in broad terms

The next phase of CTCAE reliability will likely be defined by three shifts.

1. More structured support around clinician judgment

The future is less about "automation for its own sake," and more about reducing variability in how decisions are made and documented. Tools that guide consistent interpretation, without eroding clinical accountability, will be central.

2. Clearer traceability expectations

Stakeholders across research, quality, and compliance increasingly expect that grading decisions can be reviewed with confidence. The direction of travel is toward more transparent, review-friendly processes.

3. Smarter prioritization of attention

Instead of treating all AEs as equal from an operational perspective, modern workflows will focus human effort where risk and impact are highest. This is a pragmatic way to raise quality without inflating burden.

Why this matters beyond oncologists

CTCAE performance affects more than clinical teams.

• Research operations cares about consistency, reduced back-and-forth, and reliable handoffs.

• Informatics cares about workflow fit and clean downstream data.

• Compliance and quality care about defensibility and consistency across users and sites.

• Executive sponsors care about reduced risk, stronger sponsor confidence, and scalable trial readiness.

When CTCAE grading improves, the whole enterprise benefits, not just the clinician documenting the event.

A practical takeaway

CTCAE as a standard is not broken. The challenge is the operational environment around it. The winning approach in 2025 is a balanced one, strengthen documentation habits, focus reviews on high-risk areas, and adopt tools that support clinician judgment rather than trying to replace it.

If your team wants a simple starting point, this short checklist is a good north star:

1. Identify your highest-risk AE categories and time windows.

2. Standardize the minimum context needed for confident grading.

3. Calibrate reviewers regularly using real edge cases.

4. Prioritize consistency metrics alongside speed.

5. Modernize workflows in a way that preserves clinical accountability.

Closing thought

The future of CTCAE grading will be defined by trust. The organizations that lead will not be the ones chasing maximal automation, they will be the ones building dependable, clinician-centered processes that raise consistency, reduce burden, and stand up to scrutiny.

Marc Saint-jour, MD

Chief Medical Officer

BurnaAI

marc@burna.ai