Counterfactual clinical prediction models could help to infer individualized treatment effects in randomized controlled trials—An illustration with the International Stroke Trial
Bibliographic record
Abstract
OBJECTIVE: Causal treatment effects are estimated at the population level in randomized controlled trials, while clinical decision is often to be made at the individual level in practice. We aim to show how clinical prediction models used under a counterfactual framework may help to infer individualized treatment effects. STUDY DESIGN AND SETTING: As an illustrative example, we reanalyze the International Stroke Trial. This large, multicenter trial enrolled 19,435 adult patients with suspected acute ischemic stroke from 36 countries, and reported a modest average benefit of aspirin (vs. no aspirin) on a composite outcome of death or dependency at 6 months. We derive and validate multivariable logistic regression models that predict the patient counterfactual risks of outcome with and without aspirin, conditionally on 23 predictors. RESULTS: The counterfactual prediction models display good performance in terms of calibration and discrimination (validation c-statistics: 0.798 and 0.794). Comparing the counterfactual predicted risks on an absolute difference scale, we show that aspirin-despite an average benefit-may increase the risk of death or dependency at 6 months (compared with the control) in a quarter of stroke patients. CONCLUSIONS: Counterfactual prediction models could help researchers and clinicians (i) infer individualized treatment effects and (ii) better target patients who may benefit from treatments.
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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 | 0.314 | 0.492 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.005 |
| Bibliometrics | 0.002 | 0.002 |
| Science and technology studies | 0.001 | 0.005 |
| Scholarly communication | 0.004 | 0.005 |
| Open science | 0.003 | 0.003 |
| Research integrity | 0.004 | 0.006 |
| Insufficient payload (model declined to judge) | 0.005 | 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".