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Record W3153506813 · doi:10.1038/s41467-021-22446-z

Mortality outcomes with hydroxychloroquine and chloroquine in COVID-19 from an international collaborative meta-analysis of randomized trials

2021· review· en· W3153506813 on OpenAlex
Cathrine Axfors, Andreas M. Schmitt, Perrine Janiaud, Janneke van ’t Hooft, Sherief Abd‐Elsalam, Ehab Fawzy Abdo, Benjamin S. Abella, Javed Akram, Ravi K. Amaravadi, Derek C. Angus, Yaseen M. Arabi, Shehnoor Azhar, Lindsey R. Baden, Arthur W. Baker, Leïla Belkhir, Thomas Benfield, Marvin A. H. Berrevoets, Cheng‐Pin Chen, Tsung‐Chia Chen, Shu‐Hsing Cheng, Chien‐Yu Cheng, Wei‐Sheng Chung, Yehuda Z. Cohen, Lisa N. Cowan, Olav Dalgård, Fernando Val, Marcus Lacerda, Gisely Cardoso de Melo, Lennie Derde, Vincent Dubée, Anissa Elfakir, Anthony Gordon, Carmen Margarita Hernández‐Cardenas, Thomas Hills, Andy I. M. Hoepelman, Yi-Wen Huang, Bruno Igau, Ronghua Jin, Felipe Jurado-Camacho, Khalid S. Khan, Peter G. Kremsner, Benno Kreuels, Cheng-Yu Kuo, Thuy Le, Yi‐Chun Lin, Wu-Pu Lin, Tse-Hung Lin, Magnus Nakrem Lyngbakken, Colin McArthur, Bryan J. McVerry, Patricia Meza-Meneses, Wuelton Marcelo Monteiro, Susan C. Morpeth, Ahmad Mourad, Mark J. Mulligan, Srinivas Murthy, Susanna Naggie, Shanti Narayanasamy, Alistair Nichol, Lewis A. Novack, Sean M. O’Brien, Nwora Lance Okeke, Léna Perez, Rogelio Pérez‐Padilla, Laurent Perrin, Arantxa Remigio-Luna, Norma E. Rivera-Martínez, Frank W. Rockhold, Sebastián Rodríguez‐Llamazares, Robert Rolfe, Rossana Rosa, Helge Røsjø, Vanderson de Souza Sampaio, Todd B. Seto, Muhammad Shahzad, Shaimaa Soliman, Jason E. Stout, Ireri Thirión-Romero, Andrea B. Troxel, Ting-Yu Tseng, Nicholas Turner, Robert J. Ulrich, Stephen R. Walsh, Steve Webb, Jesper M. Weehuizen, Maria Velinova, Hon-Lai Wong, Rebekah Wrenn, Fernando G. Zampieri, Wu Zhong, David Moher, Steven N. Goodman, John P. A. Ioannidis, Lars G. Hemkens

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

affAt least one author lists a Canadian institution in the pinned OpenAlex snapshot.

Bibliographic record

VenueNature Communications · 2021
Typereview
Languageen
FieldMedicine
TopicCOVID-19 Clinical Research Studies
Canadian institutionsOttawa HospitalUniversity of British Columbia
FundersSweden-America FoundationSvenska LäkaresällskapetSchweizerischer Nationalfonds zur Förderung der Wissenschaftlichen ForschungUniversität BaselNational Institute for Health and Care ResearchSanofiNational Cancer InstituteUppsala UniversitetLundbeckfondenLaura and John Arnold FoundationNational Science Foundation
KeywordsHydroxychloroquineChloroquineCoronavirus disease 2019 (COVID-19)Meta-analysis2019-20 coronavirus outbreakRandomized controlled trialSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2)MedicineBetacoronavirusPandemicMEDLINEVirologyIntensive care medicineInternal medicineBiologyMalariaImmunologyOutbreak

Abstract

fetched live from OpenAlex

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 aim to estimate the effects of hydroxychloroquine and chloroquine on survival in COVID-19 from all currently available RCT evidence, published and unpublished. We present a 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 unpublished RCTs (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, Cochrane COVID-registry up to June 11, 2020), and published RCTs (PubMed, medRxiv and bioRxiv up to October 16, 2020). All-cause mortality has been 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 and chloroquine. Prespecified subgroup analyses include patient setting, diagnostic confirmation, control type, and publication status. Sixty-three trials were potentially eligible. We included 14 unpublished trials (1308 patients) and 14 publications/preprints (9011 patients). Results for hydroxychloroquine are dominated by RECOVERY and WHO SOLIDARITY, two highly pragmatic trials, which employed relatively high doses and included 4716 and 1853 patients, respectively (67% of the total sample size). The combined OR on all-cause mortality for hydroxychloroquine is 1.11 (95% CI: 1.02, 1.20; I² = 0%; 26 trials; 10,012 patients) and for chloroquine 1.77 (95%CI: 0.15, 21.13, I² = 0%; 4 trials; 307 patients). We identified no subgroup effects. We found that treatment with hydroxychloroquine is associated with increased mortality in COVID-19 patients, and there is no benefit of chloroquine. Findings have unclear generalizability to outpatients, children, pregnant women, and people with comorbidities.

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.

Full frame distilled prediction

Teacher imitation

Not 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.

metaresearch head score (Codex)0.012
metaresearch head score (Gemma)0.250
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMetaresearch, Meta-epidemiology (narrow), Meta-epidemiology (broad)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Meta-analysis · Consensus signal: Meta-analysis
GenreCandidate signal: Review · Consensus signal: Review
Teacher disagreement score0.331
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0120.250
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0230.004
Bibliometrics0.0010.003
Science and technology studies0.0000.001
Scholarly communication0.0000.000
Open science0.0010.001
Research integrity0.0010.002
Insufficient payload (model declined to judge)0.0010.000

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.

Opus teacher head0.384
GPT teacher head0.610
Teacher spread0.226 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it