Two-part joint model for a longitudinal semicontinuous marker and a terminal event with application to metastatic colorectal cancer data
Bibliographic record
Abstract
Joint models for a longitudinal biomarker and a terminal event have gained interests for evaluating cancer clinical trials because the tumor evolution reflects directly the state of the disease. A biomarker characterizing the tumor size evolution over time can be highly informative for assessing treatment options and could be taken into account in addition to the survival time. The biomarker often has a semicontinuous distribution, i.e., it is zero inflated and right skewed. An appropriate model is needed for the longitudinal biomarker as well as an association structure with the survival outcome. In this article, we propose a joint model for a longitudinal semicontinuous biomarker and a survival time. The semicontinuous nature of the longitudinal biomarker is specified by a two-part model, which splits its distribution into a binary outcome (first part) represented by the positive versus zero values and a continuous outcome (second part) with the positive values only. Survival times are modeled with a proportional hazards model for which we propose three association structures with the biomarker. Our simulation studies show some bias can arise in the parameter estimates when the semicontinuous nature of the biomarker is ignored, assuming the true model is a two-part model. An application to advanced metastatic colorectal cancer data from the GERCOR study is performed where our two-part model is compared to one-part joint models. Our results show that treatment arm B (FOLFOX6/FOLFIRI) is associated to higher SLD values over time and its positive association with the terminal event leads to an increased risk of death compared to treatment arm A (FOLFIRI/FOLFOX6).
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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 | 0.030 | 0.033 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.004 | 0.005 |
| Bibliometrics | 0.002 | 0.002 |
| Science and technology studies | 0.001 | 0.003 |
| Scholarly communication | 0.003 | 0.002 |
| Open science | 0.004 | 0.003 |
| Research integrity | 0.003 | 0.005 |
| Insufficient payload (model declined to judge) | 0.006 | 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".