Placebo Rates in Crohn’s Disease Randomized Clinical Trials: An Individual Patient Data Meta-Analysis
Bibliographic record
Abstract
BACKGROUND & AIMS: Understanding placebo rates is critical for efficient clinical trial design. We assessed placebo rates and associated factors using individual patient data from Crohn's disease trials. METHODS: We conducted a meta-analysis of phase 2/3 placebo-controlled trials evaluating advanced therapies in moderate to severe Crohn's disease (2010-2021). Deidentified individual patient data were obtained through Vivli Inc and the Yale University Open Data Access Project. Primary outcomes were clinical response and remission. Pooled placebo rates and 95% confidence intervals (CIs) were estimated using 1- and 2-stage meta-analytic approaches. Regression analyses identified patient-level factors associated with placebo rates. RESULTS: Analysis of individual patient data from 8 induction (n = 1147) and 4 maintenance (n = 524) trials showed overall placebo clinical response and remission rates for induction were 27% (95% CI, 23%-32%) and 10% (95% CI, 8%-14%), respectively, and 32% (95% CI, 23%-42%) and 22% (95% CI, 14%-33%) for maintenance, respectively. Among biologic (bio)-naïve patients, placebo response and remission rates during induction were 29% (95% CI, 24%-35%) and 11% (95% CI, 8%-15%) respectively, and 26% (95% CI, 20%-33%) and 10% (95% CI, 8%-14%) for biologic (bio)-exposed patients, respectively. During maintenance, biologic-naïve response and remission rates were 41% (95% CI, 34%-48%) and 32% (95% CI, 24%-40%), respectively, and 29% (95% CI, 24%-34%) and 16% (95% CI, 13%-21%) for bio-exposed, respectively. Higher baseline C-reactive protein concentration predicted lower placebo rates, whereas higher baseline albumin levels and body mass index increased the odds of placebo outcomes. Increased baseline Crohn's Disease Activity Index and 2-item patient-reported outcome scores predicted higher response rates in induction, lower response rates in maintenance, and lower remission rates in induction and maintenance. CONCLUSIONS: Patient- and trial-level characteristics influence placebo rates in Crohn's disease trials. Careful implementation of eligibility criteria, outcome definitions, and patient stratification may reduce placebo rates.
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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 | 0.021 | 0.005 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.009 | 0.008 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.002 | 0.002 |
| Research integrity | 0.001 | 0.001 |
| 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".