HG-85INTER-OBSERVER AGREEMENT IN NEUROPATHOLOGICAL HGG DIAGNOSIS : EXPERIENCE OF THE PRE-RANDOMISATION CENTRAL REVIEW IN THE HERBY TRIAL
Bibliographic record
Abstract
In previous large paediatric multicentre trials for High-Grade Glioma (HGG), high proportions of diagnostic disagreement across neuropathologists were reported. The HERBY trial is a Phase-II open-label, randomised, multicentre trial evaluating bevacizumab in paediatric patients with newly diagnosed supratentorial HGG. METHODS: Confirmation of HGG diagnosis by reference pathology was mandatory before randomisation, followed by a review by five independent expert neuropathologists. Inter-observer agreement was assessed using Cohen's Kappa coefficients. RESULTS: Slides from 169/187 patients screened for eligibility were centrally reviewed, within 3 days in 69% of cases. HGG diagnosis was centrally confirmed in 149 cases (88%), whereas diagnosis was low-grade glioma in 5% (n = 8), anaplastic ganglioglioma/PXA (n = 8), miscellaneous diagnoses (n = 4). 124 patients entered the randomised trial. Three cases were not confirmed by the pathology panel (reclassified in grade II oligodendroglioma or anaplastic gangliogliomas). The Kappa coefficient between local and reference pathologist was moderate for the subtype and substantial for the WHO grade (Kappa = 0.45 and 0.68, respectively). Agreement varied according to the initial diagnosis with the confirmation of subtype and grade for 23% cases of oligodendroglioma or mixed oligo-astrocytoma, 76% of WHO grade III astrocytoma and 95% of glioblastoma. The review panel registered some degree of discordance for subtype or grade in 52% cases, with dispersed conclusions from the experts (> 3 out of 5) in 10% cases. However, Kappa coefficient reached 85% for the grading between the reference pathologist and the consensus. These data highlight the interest and feasibility of a pre-randomised real-time central neuropathological review in multicentre trials.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.501 | 0.445 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.004 | 0.002 |
| Bibliometrics | 0.001 | 0.002 |
| Science and technology studies | 0.002 | 0.003 |
| Scholarly communication | 0.004 | 0.003 |
| Open science | 0.003 | 0.005 |
| Research integrity | 0.003 | 0.002 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".