A Practical Approach in Refining Binary Outcome for Treatment Effect of COVID-19 According to Geographical Diversity

Abstract

The recent COVID-19 pandemic has drawn attention to health and economics worldwide. Initially, diseases only ravage local populations, while a pandemic could aggravate global economic burdens. Lopinavir/Ritonavir is an anti-HIV drug that was used on small scale patients during SARS, but its effectiveness for COVID-19 treatment is still unclear. Previous studies or meta-analysis have retrieved clinical data of subgroup analysis to evaluate the efficacy and safety of Lopinavir/Ritonavir for the treatment of COVID-19 in a few affected regions. However, geographical diversity and small number of studies bias correction were not achieved in such subgroup analysis of published meta-analysis. The present study demonstrates a practical approach in refining the binary outcome for COVID-19 treatment of Lopinavir/Ritonavir according to geographical location diversity and small number of studies (less than or equal to five) for subgroup analysis. After performing practical approach, the risk of adverse event with LPV/RTV for treatment of COVID-19 becomes nonsignificant compared to previous meta-analysis. Furthermore, we also notice heterogeneity of random effect of meta-analysis may be declined after proposed adjustment. In conclusion, proposed practical approach is recommend for performing a subgroup analysis to avoid concentration in a single geographical location and small number of studies bias.

Keywords: COVID-19; Lopinavir/Ritonavir; efficacy; geographical diversity; meta-analysis; safety; small number of studies bias.

Figure 1

Adjusted random effects of LPV/RTV vs. umifenovir for rate of adverse events. A total of 45 adverse events were reported in the LPV/RTV arms compared to a total of 14 adverse events found in the umifenovir group and there is 0.83 times the odds, but no significance for adverse events. CI, confidence interval; df, degrees of freedom [19,20,21].

Figure 2

Adjusted random effects of LPV/RTV vs. no antiviral treatment or conventional for rate of adverse events. A total of 45 adverse events were reported in the LPV/RTV arms compared to the total of 10 presented in no antiviral treatment or conventional arms group and there is 1.51 times the odds, but no significance for adverse events. CI, confidence interval; df, degrees of freedom [19,20,21].

Figure 3

Adjusted random effects of mean difference in time from +ve to −ve PCR (days) between LPV/RTV vs. no antiviral treatment or conventional. A total of 288 patients reported on virological cure in LPV/RTV alone arm and conventional arm on day 7 among three studies. Nonsignificant mean difference (p = 0.93) was observed between the two arms in terms. CI, confidence interval; df, degrees of freedom [19,20,23].

Figure 4

Adjusted random effects of mean difference in time from +ve to −ve PCR (days) between LPV/RTV vs. umifenovir. A total of 214 patients presented on virological cure in LPV/RTV alone arm and umifenovir arm on day 7 among three studies. No significant mean difference (p = 0.39) was found between the two arms in terms of virological cure. CI, confidence interval; df, degrees of freedom [19,20,24].

Figure 5

Adjusted random effects of mean difference in time from +ve to −ve PCR (days) between LPV/RTV vs. LPV/RTV plus umifenovir combination. A total of 168 patients reported on virological cure in LPV/RTV alone arm and umifenovir plus LPV/RTV arm on day 7 among two studies. No significant mean difference (p = 0.11) was reported between the two arms in terms of virological cure. CI, confidence interval; df, degrees of freedom [19,20].