How robust are the results of one of the first positive trials exploring hydroxychloroquine for treatment of COVID-19?
Notice bibliographique
Résumé
Abstract An outbreak of a novel human coronavirus infection emerged in Wuhan, China in December 2019. Two months later, the World Health Organization (WHO) announced SARS-CoV-2 as the name for the new virus and COVID-19 for the associated illness. On March 12, 2020, the WHO officially declared COVID-19 as a pandemic. The scientific community has raced to find effective therapeutic agents against the virus. Gautret et al 2020 is among one of the first purportedly positive trials of hydroxychloroquine for the treatment of COVID-19. However, it is imperative that a thorough analysis and understanding of trial data be undertaken prior to making claims about safety and efficacy. Our group assessed the statistical robustness of the trial using the Fragility Index (FI). The FI provides a numerical quantification of a clinical trial’s conclusions. The index is based on iterative statistical calculations to determine the minimum number of events within a trial that would theoretically need to change from positive to negative in order for the trial’s endpoint to convert from significant to non-significant; the higher the index, the more statistically robust the study results. For the Gautret et al trial, one endpoint had an FI of 1, two had indices of 2, and another had an index of 4. The primary endpoint of viral clearance on day 6 had an FI of 4. This indicates that if 4 events were to change from positive to negative, the conclusion of the trial would become mathematically non-significant. This index is comparable to many other published trials of established agents; the median FI across the reported literature appears to be 2. In conclusion, the trial results reported by Gautret et al are statistically robust, assuming that data quality is not compromised; however, the study was an open-label trial with non-homogenous groups, with analysis conducted per-protocol. Additionally, SARS-CoV-2 Reverse Transcriptase-PCR (RT-PCR) testing was not conducted in a systematic way amongst the two groups. Further analyses of this trial and future trials of antiviral agents with potential activity against SARS-CoV-2 should be performed with complementary epidemiologic and statistical techniques to determine whether the trial’s results are clinically important and/or should be explored in depth. Given the statistically robust results reported by Gautret et al, despite the study’s inherent methodological and analytical flaws, hydroxychloroquine should be studied as a potential agent against COVID-19 in larger clinical trials.
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Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,009 | 0,478 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,004 | 0,001 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,001 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,001 | 0,001 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».