One‐step validation method for surrogate endpoints using data from multiple randomized cancer clinical trials with failure‐time endpoints
Bibliographic record
Abstract
A surrogate endpoint can be used instead of the most relevant clinical endpoint to assess the efficiency of a new treatment. Before being used, a surrogate endpoint must be validated based on appropriate methods. Numerous validation approaches have been proposed with the most popular used in a context of meta‐analysis, based on a two‐step analysis strategy. For two failure‐time endpoints, two association measurements are usually used, Kendall's τ at the individual level and the adjusted coefficient of determination ( ) at the trial level. However, is not always available due to model estimation constraints. We propose a one‐step validation approach based on a joint frailty model, including both individual‐level and trial‐level random effects. Parameters have been estimated using a semiparametric penalized marginal log‐likelihood method, and various numerical integration approaches were considered. Both individual‐ and trial‐level surrogacy were evaluated using a new definition of Kendall's τ and the coefficient of determination. Estimators' performances were evaluated using simulation studies and satisfactory results were found. The model was applied to individual patient data meta‐analyses in gastric cancer to assess disease‐free survival as a surrogate for overall survival, as part of the evaluation of adjuvant therapy.
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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 | 0.178 | 0.280 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.004 | 0.008 |
| Bibliometrics | 0.004 | 0.003 |
| Science and technology studies | 0.001 | 0.002 |
| Scholarly communication | 0.003 | 0.003 |
| Open science | 0.004 | 0.003 |
| Research integrity | 0.003 | 0.004 |
| Insufficient payload (model declined to judge) | 0.004 | 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".