On the three‐arm non‐inferiority trial including a placebo with a prespecified margin
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Bibliographic record
Abstract
Three-arm trials including the experimental treatment, an active reference treatment and a placebo are recommended in the guidelines of the ICH and EMEA/CPMP as a useful approach to the assessment of assay sensitivity. Generally, the acceptable non-inferiority margin Δ has been defined as the maximum clinically irrelevant difference between treatments in many two-arm non-inferiority trials. However, many recent articles discussing three-arm trials have considered a design with unknown Δ which is the prespecified fraction f of unknown effect size of the reference drug, where the prespecified fraction f is treated as if it were a revised margin. Therefore, these methods cannot be applied to the case where the acceptable non-inferiority margin must be a prespecified difference between treatments. In this paper, we propose a statistical test procedure for three-arm non-inferiority trials with the margin Δ defined as a prespecified difference between treatments under the situation that the primary endpoints are normally distributed with a common, but unknown, variance. In addition, we derive the optimal allocation that minimizes the total sample size. The proposed method is illustrated with data on a randomized controlled trial on major depressive disorder.
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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 | 0.251 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.002 |
| Insufficient payload (model declined to judge) | 0.003 | 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 it