Type-2 biomarker elevation across asthma treatment steps in the ORACLE patient-level meta-analysis of all-comer trials
Bibliographic record
Abstract
<bold>Rationale:</bold> The relationship between asthma treatment step and prevalence of raised blood eosinophil counts (BEC) and exhaled nitric oxide (FeNO) is unclear. <bold>Aim:</bold> To assess the proportion of trial patients with raised baseline BEC and FeNO across asthma treatment steps. <bold>Methods:</bold> We included participants from the control arms of 13 randomised controlled asthma trials not enriching for biomarkers (Novel START, PRACTICAL, CAPTAIN, Dupilumab phase 2b, LAVOLTA 1-2, LUTE-VERSE, MILLY, PACT, QUEST, STRATOS 1-2; all part of the OxfoRd Asthma attaCk risk scaLE (ORACLE) patient-level meta-analysis). Proportions of patients were tabulated for baseline BEC×FeNO categories per treatment step. A proportion test assessed differences in biomarker prevalence across steps in 10 imputed datasets. <bold>Results:</bold> 4292 patients were included. Raised biomarkers occurred significantly more in mild asthma (Fig). Baseline BEC and FeNO elevation (≥0.3×109/L and ≥50 ppb) was observed in n=61/315 (27%) of step 1, 63/315 (20%) of step 2, 50/846 (6%) of step 3, 175/1635 (11%) of step 4, and 158/1271 (12%) of step 5 populations (p<2.2E-16). <bold>Conclusion:</bold> In unselected clinical trial populations, BEC and FENO elevation is seen more often in less intensely treated asthma. These results highlight the complexity between type-2 biomarker status, treatment, and clinical impact. <bold>Prospero:</bold> CRD42021245337; <bold>Funding:</bold> NIHR, QRHRN, FRQS, APQ, SAB, LUF <fig><object-id>erj;64/suppl_68/PA1210/F1</object-id><object-id>F1</object-id><object-id>F1</object-id><graphic></graphic></fig>
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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 | 0.010 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.003 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 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".