Development and Validation of Minimal Disease Activity, Disease Flare, and Minimal Clinically Important Difference for Children with Chronic Nonbacterial Osteomyelitis Using a Consensus and Data-Driven Approach
Bibliographic record
Abstract
Abstract Objectives To create definitions for minimal disease activity (MDA), flare, and minimal clinically important difference (MCID) for chronic nonbacterial osteomyelitis (CNO). It is necessary to establish these criteria prior to starting clinical effectiveness trials for therapies in CNO. Methods Three separate cohorts samples from an international observational CNO registry were presented to a panel of twenty experts in CNO, including 7 patients/caregivers via online and in-person voting using nominal group technique to define MDA, flare, and MCID, respectively. Experts classified the cases in each cohort as meeting the state for that specific cohort, ie. MDA or not, or flare or not, or meeting MCID or not. A consensus of ⩾80% was required. Results General surveys identified the most important variables to include to define MDA, flare, and MCID. Clinical improvement of 30% or more in these critical parameters and improvement of CNO Clinical Disease Activity Score (CDAS) by at least 3 were considered meaningful by providers and consensus data. Conclusions This study provides the preliminary definitions of MDA, disease flare, and MCID in CNO which can serve as targets and potential outcomes from treatments. These definitions must now be validated in other cohorts and tested in clinical trials. Key Messages WHAT IS ALREADY KNOWN ON THIS TOPIC Measurements of minimal disease activity (MDA), worsening disease activity (‘flare’), and minimally clinically important differences (MCID) in CNO are not well-established. For successful execution of clinical trials to identify effective treatment strategies in patients with CNO, standardized definitions of these terms are necessary. WHAT THIS STUDY ADDS Using data from an international real-world registry of CNO patients, we developed and validated quantitative definitions for MDA, flare, and MCID. HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY Definitions of MDA, flare, and MCID will serve as potential outcomes in future clinical trials to study effectiveness of therapies in CNO.
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How this classification was reachedexpand
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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.000 | 0.000 |
| 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 itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, 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".