A130 EVALUATING PLACEBO RATES IN EOSINOPHILIC ESOPHAGITIS RANDOMIZED CONTROLLED TRIALS: A SYSTEMATIC REVIEW AND META-ANALYSIS
Bibliographic record
Abstract
Abstract Background Eosinophilic esophagitis (EoE) is a chronic inflammatory and progressive fibrotic condition of the esophagus. There are limited treatment options for EoE and a substantial unmet need for effective and safe medical therapies. Drug development in EoE has been hampered by heterogeneous placebo response rates and uncertainty regarding appropriate endpoint configurations. Accurate characterization of placebo response in EoE randomized controlled trials (RCTs) will help inform more future efficient trial designs. Aims To conduct a systematic review and meta-analysis to characterize symptomatic, endoscopic, and histologic placebo response rates in placebo controlled EoE RCTs. Methods We updated a Cochrane systematic review and meta-analysis, searching MEDLINE, EMBASE, and CENTRAL to January 1, 2024, to identify placebo-controlled RCTs evaluating medical therapies for patients with EoE. Studies were screened independently by 2 reviewers, and full texts were then reviewed for eligibility; all data extracted in parallel. Primary outcome: pooled proportion of clinical, endoscopic, and histologic responders and remitters randomized to placebo, using an intention-to-treat approach and random-effects model. Potential sources of heterogeneity were explored using meta-regression. Results A total of 25 RCTs were included. The pooled proportion of clinical response was 40.9% [95% CI: 29.7%-52.8%] with substantial heterogeneity (I2=74.9%). On meta-regression, older age and a higher probability of being randomized 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 eos/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 mean difference in the EoE Endoscopic Reference score to placebo was -0.56 [95% CI: -0.91, -0.21]. Conclusions Over 1/3 of patients in EoE trials clinically respond to placebo and this is associated with trial design factors such as randomization ratio and trial population. Objective endoscopic and histologic measures are associated with lower placebo responses. These findings highlight the need to re-evaluate clinical trial endpoint configurations in EoE Table 1. Pooled proportion of placebo patients achieving response Abbreviations: CI confidence interval; eos eosinophils; hpf high power field Figure 3. Association between mean age of trial participants (A) and probability of receiving placebo (B) with proportion of clinical responders to placebo Funding Agencies None
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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 | 0.083 | 0.158 |
| Meta-epidemiology (narrow) | 0.005 | 0.003 |
| Meta-epidemiology (broad) | 0.035 | 0.075 |
| Bibliometrics | 0.012 | 0.010 |
| Science and technology studies | 0.001 | 0.002 |
| Scholarly communication | 0.006 | 0.005 |
| Open science | 0.004 | 0.003 |
| Research integrity | 0.005 | 0.004 |
| Insufficient payload (model declined to judge) | 0.005 | 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 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".