Joint Multistate Models for Correlated Disease Processes: Extending Approaches for Interval-Censoring, Mixed Observation Schemes, and Multiple Longitudinal Outcomes
Bibliographic record
Abstract
In diabetes and other lifelong diseases, it is not always known with certainty how chronic correlated non-fatal disease processes co-develop over time. It is also not obvious how to analyze this complex multivariate statistical problem. This thesis reviews and proposes methods that allow for the simultaneous modelling of several such processes. In a tutorial setting, it is shown that multistate and joint modelling approaches are useful for the overall research objective. Multistate models are found to be particularly applicable for questions surrounding the order and timing of disease-related processes. However, they require discretization of outcome data and possibly a very complex state space when more than two processes are modelled. In contrast, joint models can account for variations of continuous biomarkers over time and are particularly designed for modelling complex multivariate association structures. It would therefore be useful to combine elements of multistate and joint models, and the next part of the thesis develops this framework. Shared random effects can be used to link multistate and longitudinal processes, but most existing approaches assume that the multistate transition times are exactly observed. This renders them unsuitable for interval cohort studies, which are one of the most popular study designs for questions surrounding the natural history of complications. In interval cohort studies, participants are intermittently observed at regular intervals and are thus subject to mixed observation schemes where certain events are interval-censored and others are exactly observed. A novel shared random effects joint model for a longitudinal outcome and a multistate process under a mixed observation scheme is thus proposed. An appropriate likelihood function is defined and the model is fitted using a maximum likelihood framework with adaptive Gaussian quadrature. The model is assessed using simulation studies and is applied to 30-year data from the Diabetes Control and Complications Trial and Epidemiology of Diabetes Interventions and Complications study. The model is then extended to accommodate multiple longitudinal outcomes via Bayesian estimation using Hamiltonian Monte Carlo. In the end, it is shown that the novel joint multistate model gives greater insight into the natural history of a full complications process.
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How this classification was reachedexpand
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 | 0.001 | 0.024 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| 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 itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, 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".