A Proportional Hazards Mixture Cure Model for Subgroup Analysis: Inferential Method and an Application to Colon Cancer Data
Why this work is in the frame
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Bibliographic record
Abstract
When determining subgroups with heterogeneous treatment effects in cancer clinical trials, the threshold of a variable that defines subgroups is often pre-determined by physicians based on their experience, and the optimality of the threshold is not well studied, particularly when the mixture cure rate model is considered. We propose a mixture cure model that allows optimal subgroups to be estimated for both the time to event for uncured subjects and the cure status. We develop a smoothed maximum likelihood method for the estimation of model parameters. An extensive simulation study shows that the proposed smoothed maximum likelihood method provides accurate estimates. Finally, the proposed mixture cure model is applied to a colon cancer study to evaluate the potential differences in the treatment effect of levamisole plus fluorouracil therapy versus levamisole alone therapy between younger and older patients. The model suggests that the difference in the treatment effect on the time to cancer recurrence for uncured patients is significant between patients younger than 67 and patients older than 67, and the younger patient group benefits more from the combined therapy than the older patient group.
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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 | 0.002 | 0.009 |
| 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 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| 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 it