Practical implementation of the partial ordering continual reassessment method in a Phase I combination‐schedule dose‐finding trial
Why this work is in the frame
A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.
Bibliographic record
Abstract
There is a growing medical interest in combining several agents and optimizing their dosing schedules in a single trial in order to optimize the treatment for patients. Evaluating at doses of several drugs and their scheduling in a single Phase I trial simultaneously possess a number of statistical challenges, and specialized methods to tackle these have been proposed in the literature. However, the uptake of these methods is slow and implementation examples of such advanced methods are still sparse to date. In this work, we share our experience of proposing a model-based partial ordering continual reassessment method (POCRM) design for three-dimensional dose-finding in an oncology trial. In the trial, doses of two agents and the dosing schedule of one of them can be escalated/de-escalated. We provide a step-by-step summary on how the POCRM design was implemented and communicated to the trial team. We proposed an approach to specify toxicity orderings and their a-priori probabilities, and developed a number of visualization tools to communicate the statistical properties of the design. The design evaluation included both a comprehensive simulation study and considerations of the individual trial behavior. The study is now enrolling patients. We hope that sharing our experience of the successful implementation of an advanced design in practice that went through evaluations of several health authorities will facilitate a better uptake of more efficient methods in practice.
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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 | 0.015 | 0.084 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| 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 it