Meta‐Analysis: Evaluating Placebo Rates Across Outcomes in Eosinophilic Oesophagitis Randomised Controlled Trials
Bibliographic record
Abstract
ABSTRACT Background High placebo responses have limited drug development in eosinophilic oesophagitis. The optimal configuration of trial outcomes is uncertain. Aims To inform more efficient future trial designs, to characterise clinical, endoscopic and histologic placebo responses in eosinophilic oesophagitis randomised controlled trials (RCTs). Methods We updated a Cochrane systematic review and meta‐analysis, searching multiple databases to January 1, 2024, to identify placebo‐controlled RCTs evaluating medical therapies for patients with eosinophilic oesophagitis. The primary outcome was the pooled proportion of study‐defined clinical, endoscopic and histologic responders and remitters randomised to placebo, using an intention‐to‐treat approach and random‐effects model. Sources of heterogeneity were explored using meta‐regression. Results We included 25 RCTs. The pooled proportion of clinical response was 41.0% [95% CI: 29.7%–52.8%] with substantial heterogeneity (I2 = 74.9%). On meta‐regression, older age and a higher probability of being randomised to placebo reduced the likelihood of clinical response to placebo. The pooled proportion of histologic remission defined as a peak eosinophil count [PEC] ≤ 6 eosinophils per high power field [HPF] or ≤ 1 eosinophil/HPF was 4.3% [95% CI: 2.6%–6.2%] (I2 = 23.6%) and 1.3% [95% CI: 0.5%–2.5%] (I2 = 0%), respectively. The standardised mean difference in the Eosinophilic Oesophagitis Endoscopic Reference Score to placebo was −0.25 [95% CI: −0.41, −0.10]. Conclusions Over 40% of patients in eosinophilic oesophagitis trials respond clinically to placebo, and this is associated with trial design factors such as randomisation ratio and trial population. Objective endoscopic and histologic measures are associated with very low placebo responses.
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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 | 0.101 | 0.221 |
| Meta-epidemiology (narrow) | 0.006 | 0.003 |
| Meta-epidemiology (broad) | 0.032 | 0.069 |
| Bibliometrics | 0.010 | 0.009 |
| Science and technology studies | 0.001 | 0.002 |
| Scholarly communication | 0.008 | 0.005 |
| Open science | 0.004 | 0.003 |
| Research integrity | 0.006 | 0.005 |
| Insufficient payload (model declined to judge) | 0.006 | 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".