Improving drug safety predictions by reducing poor analytical practices
Bibliographic record
Abstract
Abstract Predicting the safety of a drug from preclinical data is a major challenge in drug discovery, and progressing an unsafe compound into the clinic puts patients at risk and wastes resources. In drug safety pharmacology and related fields, methods and analytical decisions known to provide poor predictions are common and include creating arbitrary thresholds, binning continuous values, giving all assays equal weight, and multiple reuse of information. In addition, the metrics used to evaluate models often omit important criteria and models’ performance on new data are often not assessed rigorously. Prediction models with these problems are unlikely to perform well, and published models suffer from many of these issues. We describe these problems in detail, demonstrate their negative consequences, and propose simple solutions that are standard in other disciplines where predictive modelling is used.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.049 | 0.213 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.004 | 0.003 |
| Science and technology studies | 0.001 | 0.002 |
| Scholarly communication | 0.007 | 0.007 |
| Open science | 0.003 | 0.005 |
| Research integrity | 0.002 | 0.004 |
| Insufficient payload (model declined to judge) | 0.003 | 0.003 |
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".