Potential treatment effects of donepezil not detected in Alzheimer's disease clinical trials: a physician survey
Bibliographic record
Abstract
OBJECTIVES: Clinical trials of the cholinesterase inhibitor donepezil have used standard psychometric tools to evaluate treatment efficacy. These trials, however, appear not to capture clinically demonstrable, but otherwise unmeasured, beneficial treatment effects. We sought to identify and categorize clinically recognizable effects of donepezil treatment in Alzheimer's disease. METHODS: A list of potential effects was developed using clinical trials data and the experience of an expert panel. These were incorporated in a questionnaire, which was tested with a focus group, revised and then used in a postal survey of physicians. Data were classified by cognitive domain, and reviewed by a second panel. RESULTS: Items that were most often rated as being improved were related to frontal systems function, including attentional capacity and initiative. Behavioral symptoms that were among the highest rated items were apathy, mood, and agitation. The top two other items were social interactions and involvement in domestic activities. Of the top ten symptomatic treatment effects, only four appeared to be readily identified by current standard measures. CONCLUSIONS: Physicians recognize as important several treatment effects that are not well captured by current standard measures. New methods are needed to capture such effects, which also have the potential to offer insight into the neurobiology of the human cholinergic system.
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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 | 0.003 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| 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) | 0.000 | 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".