Inclusion of brain volume loss in a revised measure of ‘no evidence of disease activity’ (NEDA-4) in relapsing–remitting multiple sclerosis
Why this work is in the frame
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Bibliographic record
Abstract
BACKGROUND: 'No evidence of disease activity' (NEDA), defined as absence of magnetic resonance imaging activity (T2 and/or gadolinium-enhanced T1 lesions), relapses and disability progression ('NEDA-3'), is used as a comprehensive measure of treatment response in relapsing multiple sclerosis (RMS), but is weighted towards inflammatory activity. Accelerated brain volume loss (BVL) occurs in RMS and is an objective measure of disease worsening and progression. OBJECTIVE: To assess the contribution of individual components of NEDA-3 and the impact of adding BVL to NEDA-3 ('NEDA-4') METHODS: We analysed data pooled from two placebo-controlled phase 3 fingolimod trials in RMS and assessed NEDA-4 using different annual BVL mean rate thresholds (0.2%-1.2%). RESULTS: At 2 years, 31.0% (217/700) of patients receiving fingolimod 0.5 mg achieved NEDA-3 versus 9.9% (71/715) on placebo (odds ratio (OR) 4.07; p < 0.0001). Adding BVL (threshold of 0.4%), the respective proportions of patients achieving NEDA-4 were 19.7% (139/706) and 5.3% (38/721; OR 4.41; p < 0.0001). NEDA-4 status favoured fingolimod across all BVL thresholds tested (OR 4.01-4.41; p < 0.0001). CONCLUSION: NEDA-4 has the potential to capture the impact of therapies on both inflammation and neurodegeneration, and deserves further evaluation across different compounds and in long-term studies.
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Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.006 | 0.041 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
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 it