Disease‐Modifying Trials in Treated Parkinson's Disease: “Stable Treated” Does Not Equate with Biological Stability
Bibliographic record
Abstract
Traditionally, clinical trials of putative disease-modifying therapies in Parkinson's disease have enrolled untreated patients at the earliest clinical stages of their disease. Due to a number of challenges inherent with this approach, there has been a recent move to a different study design, enrolling patients who are already taking "stable" anti-parkinson medication. However, typically, the symptomatic treatment regimen has not been defined uniformly with respect to drugs and dosages utilized or duration of therapy. More importantly, this approach fails to consider or account for the major pharmacodynamic changes induced in the parkinsonian brain by varying dopaminergic therapies (particularly levodopa) and the impact of these on both clinical and neuroimaging outcome measures. In this review, we highlight what is known about the changes induced by dopaminergic therapy and the challenges these will present in the interpretation of outcomes of studies using this trial design. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.005 | 0.002 |
| Bibliometrics | 0.001 | 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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 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; both teacher heads agree on what is shown here.
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".