Mortality outcomes with hydroxychloroquine and chloroquine in COVID-19: an international collaborative meta-analysis of randomized trials
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Bibliographic record
Abstract
Abstract Background Substantial COVID-19 research investment has been allocated to randomized clinical trials (RCTs) on hydroxychloroquine/chloroquine, which currently face recruitment challenges or early discontinuation. We aimed to estimate the effects of hydroxychloroquine and chloroquine on survival in COVID-19 from all currently available RCT evidence, published and unpublished. Methods: Rapid meta-analysis of ongoing, completed, or discontinued RCTs on hydroxychloroquine or chloroquine treatment for any COVID-19 patients (protocol: https://osf.io/QESV4/ ). We systematically identified published and unpublished RCTs by September 14, 2020 (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, PubMed, Cochrane COVID-19 registry). All-cause mortality was extracted (publications/preprints) or requested from investigators and combined in random-effects meta-analyses, calculating odds ratios (ORs) with 95% confidence intervals (CIs), separately for hydroxychloroquine/chloroquine. Prespecified subgroup analyses included patient setting, diagnostic confirmation, control type, and publication status. Results Sixty-two trials were potentially eligible. We included 16 unpublished trials (1596 patients) and 10 publications/preprints (6317 patients). The combined summary OR on all-cause mortality for hydroxychloroquine was 1.08 (95%CI: 0.99, 1.18; I 2 =0%; 24 trials; 7659 patients) and for chloroquine 1.77 (95%CI: 0.15, 21.13, I 2 =0%; 4 trials; 307 patients). We identified no subgroup effects. Conclusions We found no benefit of hydroxychloroquine or chloroquine on the survival of COVID-19 patients. For hydroxychloroquine, the confidence interval is compatible with increased mortality (OR 1.18) or negligibly reduced mortality (OR 0.99). Findings have unclear generalizability to outpatients, children, pregnant women, and people with comorbidities.
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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 | 0.021 | 0.388 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.016 | 0.003 |
| Bibliometrics | 0.001 | 0.002 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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 it