To the Editor,
We thank Beccacece et al. for their letter to the editor notifying that a study that we included in our recent meta-analysis has since been retracted. We believe that it is paramount to avoid citing retracted works, particularly in meta-analyses [1]. With respect to our publication [2], we originally conducted a sensitivity analysis that excluded the now-retracted trial, as it was at a high risk of bias; however, the sensitivity analysis did not include the final results of the WHO Solidarity trial [3]. To that end, we have updated our analysis herein. All patients in the retracted study were originally included in the supplemental oxygen without ventilation group; therefore, it is the only subgroup that has changed. In the original analysis, the frequentist meta-analysis yielded a relative risk in this subgroup of 0.89 (95% CI, 0.79–0.99). The corresponding Bayesian meta-analysis on the risk difference scale estimated the probability of any and ≥1% mortality benefit at 93.7% and 77.4%, respectively. The revised frequentist random-effects meta-analysis (Fig. 1 ) now finds a relative risk within the subgroup of 0.88 (95% CI, 0.78–0.99). The Bayesian probability density function for patients in that specific subgroup (Fig. 2 ) now finds probabilities of any and ≥1% mortality benefit of 95.5% and 83.2%, respectively.
Fig. 1.
Random-effects meta-analysis stratified by oxygenation requirements. ACTT, Adaptive Covid-19 Treatment Trial; CATCO, Canadian Treatments for COVID-19. ∗Excludes patients already reported in the Solidarity 1 (NEJM 2020) and CATCO (CMAJ 2022) trials. ∗∗Excludes patients reported in the Solidarity 1 (NEJM 2022) trial.
Fig. 2.
Probability density functions for combined posterior distributions of the included remdesivir trials in patients requiring supplemental oxygen without mechanical ventilation. AUC, area under the curve.
The conclusions of the original paper are unchanged; however, these figures and numbers should now supersede those presented in the original paper. The issue of how to address results that are retracted after their inclusion in a published meta-analysis needs to be better addressed by the scientific community at large.
Author contributions
T.C.L. is the lead author, and E.G.M. is the senior author. The contributions to the paper are as follows. Conceptualization: T.C.L. and E.G.M.; methodology: T.C.L.; validation: T.C.L.; formal analysis: T.C.L.; data curation: T.C.L.; writing: T.C.L. and E.G.M.; and visualization: T.C.L.
Transparency declaration
T.C.L. was a co-investigator on CATCO, the Canadian arm of the WHO Solidarity trial, which was funded by the Canadian Institutes of Health Research grant numbers 422549, 446637, and 424701. T.C.L. and E.G.M. receive research salary support from the Fonds de Recherche Québec - Santé. The funders had no influence on the conduct or content of this article.
Editor: L. Leibovici
References
- 1.Lee T.C., Senecal J., Hsu J.M., McDonald E.G. Ongoing citations of a retracted study involving cardiovascular disease, drug therapy, and mortality in COVID-19. JAMA Intern Med. 2021;181:1535–1537. doi: 10.1001/jamainternmed.2021.4112. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Lee T.C., Murthy S., Corpo O.D., Senécal J., Butler-Laporte G., Sohani Z.N., et al. Remdesivir for the treatment of COVID-19: a systematic review and meta-analysis. Clin Microbiol Infect. 2022;28:1203–1210. doi: 10.1016/j.cmi.2022.04.018. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.WHO Solidarity Trial Consortium Remdesivir and three other drugs for hospitalised patients with COVID-19: final results of the WHO Solidarity randomised trial and updated meta-analyses. Lancet. 2022;399:1941–1953. doi: 10.1016/S0140-6736(22)00519-0. [DOI] [PMC free article] [PubMed] [Google Scholar]