To evaluate for COVID-19 treatments without benefits in subsequent large RCTs how many of their most-cited clinical studies had declared favorable results.
Scopus searches (December 23, 2021) identified articles on lopinavir-ritonavir, hydroxycholoroquine, azithromycin, remdesivir, convalescent plasma, colchicine or interferon (index interventions) that represented clinical trials and had >150 citations. Their conclusions were correlated with study design features. The ten most recent citations for the most-cited article on each index intervention were examined on whether they were critical to the highly-cited study. Altmetric scores were also obtained.
40 eligible articles of clinical studies had received >150 citations. 20/40 (50%) had favorable conclusions, 4 were equivocal. Highly-cited articles with favorable conclusions were rarely RCTs (3/20) while those without favorable conclusions were mostly RCTs (15/20, p=0.0003). Only 1 RCT with favorable conclusions had >160 patients. Citation counts correlated strongly with Altmetric scores, especially news items. Only 9 (15%) of 60 recent citations to the most highly-cited studies with favorable or equivocal conclusions were critical.
Many clinical studies with favorable conclusions for largely ineffective COVID-19 treatments are uncritically heavily cited and disseminated. Early observational studies and small randomized trials may cause spurious claims of effectiveness that get perpetuated.
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