Comparison of Selected Methods for Modeling of Multi-State Disease Progression Processes: A Simulation Study
Bibliographic record
Abstract
Prognostic studies are essential to understand the role of particular prognostic factors and, thus, improve prognosis. In most studies, disease progression trajectories of individual patients may end up with one of mutually exclusive endpoints or can involve a sequence of different events. One challenge in such studies concerns separating the effects of putative prognostic factors on these different endpoints and testing the differences between these effects. In this article, we systematically evaluate and compare, through simulations, the performance of three alternative multivariable regression approaches in analyzing competing risks and multiple-event longitudinal data. The three approaches are: (1) fitting separate event-specific Cox's proportional hazards models; (2) the extension of Cox's model to competing risks proposed by Lunn and McNeil; and (3) Markov multi-state model. The simulation design is based on a prognostic study of cancer progression, and several simulated scenarios help investigate different methodological issues relevant to the modeling of multiple-event processes of disease progression. The results highlight some practically important issues. Specifically, the decreased precision of the observed timing of intermediary (non fatal) events has a strong negative impact on the accuracy of regression coefficients estimated with either the Cox's or Lunn-McNeil models, while the Markov model appears to be quite robust, under the same circumstances. Furthermore, the tests based on both Markov and Lunn-McNeil models had similar power for detecting a difference between the effects of the same covariate on the hazards of two mutually exclusive events. The Markov approach yields also accurate Type I error rate and good empirical power for testing the hypothesis that the effect of a prognostic factor on changes after an intermediary event, which cannot be directly tested with the Lunn-McNeil method. Bootstrap-based standard errors improve the coverage rates for Markov model estimates. Overall, the results of our simulations validate Markov multi-state model for a wide range of data structures encountered in prognostic studies of disease progression, and may guide end users regarding the choice of model(s) most appropriate for their specific application.
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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 | 0.017 | 0.040 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.002 |
| Bibliometrics | 0.002 | 0.002 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.002 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.002 | 0.002 |
| Insufficient payload (model declined to judge) | 0.002 | 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 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".