The hidden variables problem in Alzheimer's disease clinical trial design
Bibliographic record
Abstract
As the leading cause of dementia worldwide, Alzheimer's disease has garnered intense academic and clinical interest. Yet, trials in search of a disease-modifying therapy have failed overwhelmingly. We suggest that, in part, this may be attributable to the influence of disruptive variables inherent to the framework of a clinical trial. Specifically, we observe that everyday factors such as diet, education, mental exertion, leisure participation, multilingualism, sleep, trauma, and physical activity, as well as clinical/study parameters including environment, family coaching, concurrent medications, and illnesses may serve as potent confounders, disruptors, or sources of bias to an otherwise significant drug-disease interaction. This perspective briefly summarizes the potential influence of these hidden variables on the outcomes of clinical trials and suggests strategies to abate their impact.
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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 | 0.418 | 0.524 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.009 | 0.007 |
| Bibliometrics | 0.002 | 0.004 |
| Science and technology studies | 0.001 | 0.006 |
| Scholarly communication | 0.006 | 0.005 |
| Open science | 0.005 | 0.003 |
| Research integrity | 0.007 | 0.008 |
| Insufficient payload (model declined to judge) | 0.008 | 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; the direct Gemma label and the distilled Codex classifier 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".