P4–373: Donepezil in Alzheimerdisease: Evaluating clinical meaningfulness
Bibliographic record
Abstract
The standard outcome measures used in clinical trials of cholinesterase inhibitors (ChEIs) often do not capture all the improvements that can be detected by clinicians or caregivers. (Winblad et al., 2001) We undertook a 24–week Canadian open–label multi–centre study to see which symptoms respond to treatment among patients starting donepezil for Alzheimer disease (AD). Patients with of mild to moderate AD (n= 101; 71 women, mean age 76.7±6.9) were assessed with the TOPS checklist, a clinical scale covering 27 symptoms identified as frequently alleviated by donepezil (Rockwood et al., 2004). Each symptom was rated at baseline for its severity by both clinicians and caregivers, using two separate 7–point Likert–type scales. For each symptom, changes from baseline were later rated separately by the clinician and the caregiver, at week 4, 12 and 24, as one of Absence; Emergence; Increase; Stability; Decrease; Cessation. Secondary outcomes included common standard scales, exploring cognition (ADAS–cog, MMSE), activities of daily living (DAD), behavioral symptoms (NPI), functions (FRS), caregiver activity survey (CAS), and the clinician's impression of change (CIBIC+). Statistical analyses were performed on the intent to treat population with last observation carried forward (LOCF). Four symptoms were reported most often: problems in remembering (97%), temporal orientation (89%), repetitiveness (85%), and cognitive activation (84%) and 8 more were identified, by both clinicians and caregivers, in ∼2/3 of patients. In 4 patients, most symptoms worsened, in 34 patients there was no change or worsening of one symptom; one or more symptoms improved without any worsening in 43 and most improved in 20. Patients with the greatest symptomatic improvement also improved most on the ADAS–Cog and the other standard measures, whereas no improvement (or decline) in each standard measure was observed in people whose symptoms did not improve or worsened. In this open–label study, donepezil treatment for 6 months was associated with symptomatic improvement in most patients with mild to moderate AD. This improvement was better detected by the TOPS checklist than by the standard scales used in regulatory studies. Symptoms indicating executive dysfunction were particularly susceptible to benefit from donepezil treatment.
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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 | 0.004 | 0.009 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.002 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.015 | 0.001 |
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".