Reply to Lipworth and Chan
Bibliographic record
Abstract
described in other randomized controlled trials, including the DREAM (Dose Ranging Efficacy And safety with Mepolizumab in severe asthma) study investigating mepolizumab in severe eosinophilic asthma (3).How can we explain this disconnect?First, the cellular and molecular mechanisms driving exacerbations versus day-to-day symptoms and QoL might differ (4).Second, in randomized controlled trials of uncontrolled asthma, there is an important improvement in symptoms and QoL in the placebo arm due to a combination of the placebo effect, the Hawthorne effect, and the natural history of the disease.Therefore, even though improvements in asthma QoL scores from baseline to week 52 were observed with tezepelumab in the PATHWAY and NAVIGATOR studies, and were most pronounced in type 2 high asthma, the improvement compared with placebo did not reach the minimal clinically important difference.This contrasts with real-life effectiveness studies that compared clinical outcomes in real-world settings before and during treatment (i.e., pre-vs.posttreatment).Intriguingly, the placebo effect has been shown to have a stronger effect on subjective outcomes such as symptoms and QoL than on objective outcomes such as exacerbations and lung function (5).In conclusion, when investigating the discordance between improvements in exacerbations as opposed to patient-reported outcomes in severe asthma treated with tezepelumab or other monoclonal antibodies, the mechanisms of disease pathophysiology as well as the principles of study design need to be taken into account.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.024 | 0.138 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.004 | 0.003 |
| Bibliometrics | 0.002 | 0.002 |
| Science and technology studies | 0.003 | 0.006 |
| Scholarly communication | 0.006 | 0.009 |
| Open science | 0.005 | 0.004 |
| Research integrity | 0.044 | 0.067 |
| Insufficient payload (model declined to judge) | 0.013 | 0.013 |
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".