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Safety and efficacy of hydroxychloroquine as prophylactic against COVID-19 in healthcare workers: a meta-analysis of randomised clinical trials

Hong et al., BMJ Open, doi:10.1136/bmjopen-2022-065305, PROSPERO CRD42021285093
Jun 2023  
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Study does not match registration: outcomes, search sources, exclusions, statistical analysis, and the cutoff date have changed. Efficacy seen without the post-hoc HCW restriction.
Meta analysis of 10 RCTs showing lower COVID-19 cases with HCQ, without statistical significance.
This analysis is missing Nasri, Seet. Statistically significant efficacy is seen with analysis of all studies, p = 0.0066
Authors include only studies with healthcare workers, which excludes Seet. This is a protocol violation - the pre-registered protocol has no restriction or mention of healthcare workers.
Authors report a 67% probability of efficacy for the lab-confirmed analysis (Bayesian posterior probability of OR<1). Notably authors do not report the probability for the suspected COVID-19 analysis, which is higher.
All PEP studies are not included Barnabas, Boulware, Dhibar, Mitjà, inclusion of PEP RCTs further increases confidence in efficacy, p = 0.0049, as does inclusion of all PrEP studies, p < 0.0000001 (B).
Authors claim Seet has moderate risk of bias, however trials with more significant issues were included. Authors state: "HCQ does not reduce the risk of confirmed or probable SARS-CoV-2 infection". This is false, authors found reduced risk, just without statistical significance due to the exclusion of studies.
Author's bayesian analysis, with details unspecified in the pre-registration, provides flexibility to alter the results. Notably, a standard DerSimonian and Laird random effects analysis is much closer to statistical significance - 0.78 [0.59-1.02] p=0.07 for suspected COVID-19.
This study includes authors with extreme conflicts of interest that have coauthored other COVID-19 trials with many critical issues, including impossible and inconsistent data. For example see issues with Boulware, Naggie, Reis.
7 meta analyses show significant improvements with hydroxychloroquine for mortality Landsteiner de Sampaio Amêndola, Risch, Risch (B), Stricker, hospitalization Landsteiner de Sampaio Amêndola, recovery Prodromos, combined death/hospitalization/cases Ladapo, and cases García-Albéniz.
Currently there are 38 HCQ for COVID-19 early treatment studies, showing 72% lower mortality [59‑81%], 67% lower ventilation [-710‑99%], 28% lower ICU admission [-17‑55%], and 41% lower hospitalization [28‑51%].
Hong et al., 16 Jun 2023, peer-reviewed, 15 authors, trial PROSPERO CRD42021285093.
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Safety and efficacy of hydroxychloroquine as prophylactic against COVID-19 in healthcare workers: a meta-analysis of randomised clinical trials
Hwanhee Hong, Anne Friedland, Mengyi Hu, Kevin J Anstrom, Susan Halabi, John E Mckinnon, Ravi Amaravadi, Jorge Rojas-Serrano, Benjamin S Abella, Angélica Margarita Portillo-Vázquez, Christopher W Woods, Adrian F Hernandez, David R Boulware, Susanna Naggie, Radha Rajasingham
BMJ Open, doi:10.1136/bmjopen-2022-065305
Objective We studied the safety and efficacy of hydroxychloroquine (HCQ) as pre-exposure prophylaxis for COVID-19 in healthcare workers (HCWs), using a metaanalysis of randomised controlled trials (RCTs). Data sources PubMed and EMBASE databases were searched to identify randomised trials studying HCQ. Study selection Ten RCTs were identified (n=5079 participants). Data extraction and synthesis The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were used in this systematic review and metaanalysis between HCQ and placebo using a Bayesian random-effects model. A pre-hoc statistical analysis plan was written. Main outcomes The primary efficacy outcome was PCRconfirmed SARS-CoV-2 infection and the primary safety outcome was incidence of adverse events. The secondary outcome included clinically suspected SARS-CoV-2 infection. Results Compared with placebo, HCWs randomised to HCQ had no significant difference in PCR-confirmed SARS-CoV-2 infection (OR 0.92, 95% credible interval (CI): 0.58, 1.37) or clinically suspected SARS-CoV-2 infection (OR 0.78, 95% CI: 0.57, 1.10), but significant difference in adverse events (OR 1.35, 95% CI: 1.03, 1.73). Conclusions and relevance Our meta-analysis of 10 RCTs investigating the safety and efficacy of HCQ as preexposure prophylaxis in HCWs found that compared with placebo, HCQ does not significantly reduce the risk of confirmed or clinically suspected SARS-CoV-2 infection, while HCQ significantly increases adverse events. PROSPERO registration number CRD42021285093.
Competing interests All authors except BSA reported no financial relationship with commercial interest. BSA has received NIH funds for COVID-19-related research and holds equity in VOC Health, a start-up company that is developing novel COVID-19 testing. Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research. Patient consent for publication Not required. Ethics approval Ethics approval was not required because this study used publicly available aggregate data that were not involved with patients' information or prospective data collection. Provenance and peer review Not commissioned; externally peer reviewed. Data availability statement All data relevant to the study are included in the article or uploaded as supplemental information. Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or..
Abella, Jolkovsky, Biney, Efficacy and safety of hydroxychloroquine vs placebo for pre-exposure SARS-Cov-2 prophylaxis among health care workers: a randomized clinical trial, JAMA Intern Med, doi:10.1001/jamainternmed.2020.6319
Core, Inference from Iterative simulation using multiple sequences, doi:10.1214/ss/1177011136
Developent, Rstan: the R interface to Stan. R Package Version
Egger, Smith, Schneider, Bias in meta-analysis detected by a simple, graphical test, BMJ, doi:10.1136/bmj.315.7109.629
Ferreira, Ludes, Diemunsch, Bayesian predictive probabilities: a good way to monitor clinical trials, Br J Anaesth, doi:10.1016/j.bja.2020.08.062
García-Albéniz, Amo, Polo, Systematic review and meta-analysis of randomized trials of hydroxychloroquine for the prevention of COVID-19, Eur J Epidemiol, doi:10.1007/s10654-022-00891-4
Grau-Pujol, Camprubí-Ferrer, Marti-Soler, Pre-exposure prophylaxis with hydroxychloroquine for COVID-19: a double-blind, placebo-controlled randomized clinical trial, Trials, doi:10.1186/s13063-021-05758-9
Halabi, Zhou, He, Landscape of Coronavirus disease 2019 clinical trials: new frontiers and challenges, Clin Trials, doi:10.1177/17407745221105106
Higgins, Thompson, Quantifying heterogeneity in a Meta-Analysis, Statist Med, doi:10.1002/sim.v21:11
Hong, Carlin, Shamliyan, Comparing Bayesian and Frequentist approaches for multiple outcome mixed treatment comparisons, Med Decis Making, doi:10.1177/0272989X13481110
Hong, Chu, Zhang, A Bayesian missing data framework for generalized multiple outcome mixed treatment comparisons, Res Syn Meth, doi:10.1002/jrsm.1153
Hong, Wang, Rosner, Meta-analysis of rare adverse events in randomized clinical trials: Bayesian and Frequentist methods, Clin Trials, doi:10.1177/1740774520969136
Hutton, Salanti, Caldwell, The PRISMA extension statement for reporting of systematic reviews incorporating network meta-analyses of health care interventions: checklist and explanations, Ann Intern Med, doi:10.7326/M14-2385
Infante, Ricordi, Hydroxychloroquine to prevent SARS-Cov-2 infection among Healthcare workers: early termination of a phase 3, randomised, open-label, controlled clinical trial, Expert Rev Anti Infect Ther, doi:10.1186/s13104-023-06281-7
Kalil, Treating COVID-19-off-label drug use, compassionate use, and randomized clinical trials during Pandemics, JAMA, doi:10.1001/jama.2020.4742
Lofgren, Nicol, Bangdiwala, Safety of hydroxychloroquine among outpatient clinical trial participants for covid-19, Open Forum Infectious Diseases, doi:10.1093/ofid/ofaa500
Mccreary, Pogue, Pharmacists. Coronavirus disease 2019 treatment: A review of early and emerging options, Open Forum Infect Dis, doi:10.1093/ofid/ofaa105
Mckinnon, Wang, Zervos, Safety and tolerability of hydroxychloroquine in health care workers and first responders for the prevention of COVID-19: WHIP COVID-19 study, Int J Infect Dis, doi:10.1016/j.ijid.2021.12.343
Nabaggala, Nair, Gacic-Dobo, The global inequity in COVID-19 vaccination coverage among health and care workers, Int J Equity Health, doi:10.1186/s12939-022-01750-0
Naggie, Milstone, Castro, Hydroxychloroquine for pre-exposure prophylaxis of COVID-19 in health care workers: a randomized, multicenter, placebo-controlled trial Healthcare worker exposure response and outcomes of hydroxychloroquine (HERO-HCQ), Int J Infect Dis, doi:10.1016/j.ijid.2023.01.019
Padma, COVID vaccines to reach poorest countries in 2023-despite recent pledges, Nature, doi:10.1038/d41586-021-01762-w
Polo, García-Albéniz, Terán, Daily tenofovir disoproxil fumarate/Emtricitabine and hydroxychloroquine for pre-exposure prophylaxis of COVID-19: a double-blind placebo-controlled randomized trial in Healthcare workers, Clin Microbiol Infect, doi:10.1016/j.cmi.2022.07.006
Puhan, Schünemann, Murad, A GRADE working group approach for rating the quality of treatment effect estimates from network meta-analysis, BMJ, doi:10.1136/bmj.g5630
Rajasingham, Bangdiwala, Nicol, Hydroxychloroquine as pre-exposure prophylaxis for Coronavirus disease 2019 (COVID-19) in Healthcare workers: A randomized trial, Clin Infect Dis, doi:10.1093/cid/ciaa1571
Rojas-Serrano, Portillo-Vásquez, Thirion-Romero, Hydroxychloroquine for prophylaxis of COVID-19 in health workers: a randomized clinical trial, PLoS One, doi:10.1371/journal.pone.0261980
Seet, Quek, Ooi, Positive impact of oral hydroxychloroquine and Povidone-iodine throat spray for COVID-19 prophylaxis: an open-label randomized trial, Int J Infect Dis, doi:10.1016/j.ijid.2021.04.035
Skipper, Pastick, Engen, Hydroxychloroquine in Nonhospitalized adults with early COVID-19: A randomized trial, Ann Intern Med, doi:10.7326/M20-4207
Sterne, Savović, Page, Rob 2: a revised tool for assessing risk of bias in randomised trials, BMJ, doi:10.1136/bmj.l4898
Syed, Hassan, Arif, Pre-exposure prophylaxis with various doses of hydroxychloroquine among Healthcare personnel on June 18, 2023 by guest, Cureus, doi:10.7759/cureus.20572
The, Group, RECOVERY collaborative group, effect of hydroxychloroquine in hospitalized patients with COVID-19, N Engl J Med, doi:10.1056/NEJMoa2022926
Vijayaraghavan, Jha, Rajbhandari, Hydroxychloroquine plus personal protective equipment versus personal protective equipment alone for the prevention of laboratoryconfirmed COVID-19 infections among Healthcare workers: a Multicentre, parallel-group randomised controlled trial from India, BMJ Open, doi:10.1136/bmjopen-2021-059540
Wang, Cao, Zhang, Remdesivir and chloroquine effectively inhibit the recently emerged novel Coronavirus (2019-nCoV) in vitro, Cell Res, doi:10.1038/s41422-020-0282-0
Watanabe, Opper, Asymptotic equivalence of Bayes cross validation and widely applicable information criterion in singular learning theory, J Mach Learn Res
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