A Meta-Analysis on the Effects of Hydroxychloroquine on COVID-19

Hussain, Nowair; Chung, Emily Q.; Heyl, Jonathan J; Hussain, Bisma; Oh, Michael C.; Pinon, Candis; Boral, Soumya; Chun, David S.; Babu, Benson A.

doi:10.7759/cureus.10005

Cited by 10 publications

(10 citation statements)

References 23 publications

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“…Moreover, some meta-analyses pooled unadjusted effect estimates of the included studies, which result in a very biased results (31) . Only three authors (35)(36)(37) included only RCTs in their meta-analyses similar to us; however, in contrast to ours, these meta-analyses were Accepted Article small (included 4-7 RCTs). One meta-analysis by Hussain et al (36) had a total of 381 patient with only two trials (111 patients) had data on mortality.…”

Section: Main Findingsmentioning

confidence: 83%

“…Only three authors (35)(36)(37) included only RCTs in their meta-analyses similar to us; however, in contrast to ours, these meta-analyses were Accepted Article small (included 4-7 RCTs). One meta-analysis by Hussain et al (36) had a total of 381 patient with only two trials (111 patients) had data on mortality. The second meta-analysis by Pathak et al (35) pooled different clinical outcomes together as a composite endpoint.…”

Section: Main Findingsmentioning

confidence: 83%

“…Although several meta-analyses addressing the role of HCQ in COVID-19 disease have been published (30)(31)(32)(33)(34)(35)(36) among others, in all of these meta-analyses, the bulk of their data were derived from observational studies, with the exception of 3 studies. Many of these observational studies suffer from serious methodological weaknesses, including treatment selection bias, immortal time bias, competing risk bias and residual confounding.…”

Section: Main Findingsmentioning

confidence: 99%

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Mortality, viral clearance, and other clinical outcomes of hydroxychloroquine in COVID‐19 patients: A systematic review and meta‐analysis of randomized controlled trials

Kashour

Gerberi

et al. 2021

Clinical Translational Sci

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Many meta‐analyses have been published about the efficacy of Hydroxychloroquine (HCQ) in COVID‐19. Most of them included observational studies, and few have assessed HCQ as a prophylaxis or evaluated its safety profile. We searched multiple databases and preprint servers for randomized controlled trials (RCTs) that assessed HCQ for the treatment or prevention of COVID‐19. We summarized the effect of HCQ on mortality, viral clearance, and other clinical outcomes. Out of 768 papers screened, 21 RCTs with a total of 14,138 patients were included. A total of 9 inpatient and 3 outpatient RCTs assessed mortality in 8,596 patients with a pooled risk difference of 0.01 [95% CI 0.00, 0.03, I2= 1%, P=0.07]. Six studies assessed viral clearance at 7 days with a pooled risk ratio (RR) of 1.11 [95% CI 0.86, 1.42, I2= 61%, P=0.44] and 5 studies at 14 days with a pooled RR of 0.96 [95% CI 0.89, 1.04, I2= 0%, P=0.34]. Several trials showed no significant effect of HCQ on other clinical outcomes and. Five prevention RCTs with 5012 patients found no effect of HCQ on the risk of acquiring COVID‐19. Thirteen trials showed that HCQ was associated with increased risk of adverse events. We observed, with high level of certainty of evidence, that HCQ is not effective in reducing mortality in COVID‐19 patients. Lower certainty evidence also suggests that HCQ neither improves viral clearance and other clinical outcomes, nor prevents COVID‐19 infection in patients with high‐risk exposure. HCQ is associated with an increased rate of adverse events.

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Section: Main Findingsmentioning

confidence: 83%

Section: Main Findingsmentioning

confidence: 83%

Section: Main Findingsmentioning

confidence: 99%

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Mortality, viral clearance, and other clinical outcomes of hydroxychloroquine in COVID‐19 patients: A systematic review and meta‐analysis of randomized controlled trials

Kashour

Gerberi

et al. 2021

Clinical Translational Sci

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“…Hydroxychloroquine was also considered in COVID-19 treatment because of previous research on SARS-CoV infection in 2002, as well as results regarding its in vitro inhibitory effects on SARS-CoV-2 replication [ 53 , 54 ]. However, hydroxychloroquine did not show significant benefits to standard care in COVID-19 [ 55 ] according to research including five randomized control trials [ 56 ]; moreover, hydroxychloroquine-related side effects were considered [ 57 ]. The hydroxychloroquine recommendation for COVID-19 treatment was, therefore, stopped [ 58 ].…”

Section: Discussionmentioning

confidence: 99%

Perceptions of Romanian Physicians on Lockdowns for COVID-19 Prevention

Dima

Balaban

Jurcuţ³

et al. 2021

Healthcare

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The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease (COVID-19) was declared a pandemic in March 2020, triggering important changes for the entire society and healthcare systems, as well as significant lockdown measures aimed to limit the disease spread. We herein intended to catch the dynamic of Romanian physicians’ perceptions of COVID-19 impact. For this purpose, after a literature review, a 30-item questionnaire was designed. The questionnaire was twice distributed online, about 1 month apart, during which partial relaxation measures were decreed in Romania. The questionnaire was voluntarily filled in by Romanian physicians who were willing to participate in the study. A total of 214 physicians answered the questionnaire upon its first release, and 199 respondents were registered upon its second release, most of whom (94.9%) were involved in clinical work, with one-third working in units dedicated to COVID-19 patients. In parallel with the relaxation of lockdown measures, along with increased confidence in the efficiency of protective measures (46.7% vs. 31.3%), separation from household members decreased from 36.9% to 22.1%. Nevertheless, the feeling of rejection felt by doctors remained similar (22.4% vs. 24.6%). Furthermore, answers regarding the clinical picture, diagnostic approach, and treatment options are discussed. Most of therapeutic options considered for SARS-CoV-2 treatment (e.g., lopinavir/ritonavir, oseltamivir, hydroxychloroquine, azithromycin, tocilizumab, and convalescent plasma) failed to confirm significant efficiency. On the contrary, vaccines for widescale use are already available despite the initial skepticism. In the beginning of the pandemic, 25.2% (18.2% vs. 32.2%) considered that there will not be an effective COVID-19 vaccine, while 41.6% (43.0% vs. 40.2%) thought that a vaccine would be available after at least 12 months. In conclusion, initially, following only a 1 month period, Romanian physicians’ intention to consider treatments such as hydroxychloroquine or lopinavir/ritonavir for COVID-19 decreased significantly. Moreover, confidence in the efficiency of available protective measures increased, and the rates of separation from household members decreased.

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“…In both meta-analyses, the selection of included studies, the degree of heterogeneity in these analyses, and the calculations of effect sizes make the veracity of the estimates uncertain. Many of the meta-analyses published had low statistical power, untreated heterogeneity and none used tools to evaluate potential risks of p-hacking (13,(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46)52).…”

Section: Publication Bias Visible On Funnel Plotmentioning

confidence: 99%

Keeping Meta-Analyses Hygienic During the COVID-19 Pandemic

Boudesseul

Zerhouni

Harbert

et al. 2021

Front. Public Health

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Despite the massive distribution of different vaccines globally, the current pandemic has revealed the crucial need for an efficient treatment against COVID-19. Meta-analyses have historically been extremely useful to determine treatment efficacy but recent debates about the use of hydroxychloroquine for COVID-19 patients resulted in contradictory meta-analytical results. Different factors during the COVID-19 pandemic have impacted key features of conducting a good meta-analysis. Some meta-analyses did not evaluate or treat substantial heterogeneity (I2 > 75%); others did not include additional analysis for publication bias; none checked for evidence of p–hacking in the primary studies nor used recent methods (i.e., p-curve or p-uniform) to estimate the average population-size effect. These inconsistencies may contribute to contradictory results in the research evaluating COVID-19 treatments. A prominent example of this is the use of hydroxychloroquine, where some studies reported a large positive effect, whereas others indicated no significant effect or even increased mortality when hydroxychloroquine was used with the antibiotic azithromycin. In this paper, we first recall the benefits and fundamental steps of good quality meta-analysis. Then, we examine various meta-analyses on hydroxychloroquine treatments for COVID-19 patients that led to contradictory results and causes for this discrepancy. We then highlight recent tools that contribute to evaluate publication bias and p-hacking (i.e., p-curve, p-uniform) and conclude by making technical recommendations that meta-analyses should follow even during extreme global events such as a pandemic.

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A Meta-Analysis on the Effects of Hydroxychloroquine on COVID-19

Cited by 10 publications

References 23 publications

Mortality, viral clearance, and other clinical outcomes of hydroxychloroquine in COVID‐19 patients: A systematic review and meta‐analysis of randomized controlled trials

Mortality, viral clearance, and other clinical outcomes of hydroxychloroquine in COVID‐19 patients: A systematic review and meta‐analysis of randomized controlled trials

Perceptions of Romanian Physicians on Lockdowns for COVID-19 Prevention

Keeping Meta-Analyses Hygienic During the COVID-19 Pandemic

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