Our study has several limitations. The association of decreased survival with hydroxychloroquine or chloro-quine treatment regimens should be interpreted cautiously. Due to the observational study design, we cannot exclude the possibility of unmeasured con-founding factors, although we have reassuringly noted consistency between the primary analysis and the propensity score matched analyses. Nevertheless, a cause-and-effect relationship between drug therapy and survival should not be inferred. These data do not apply to the use of any treatment regimen used in the ambulatory, out-of-hospital setting. Randomised clinical trials will be required before any conclusion can be reached regarding benefit or harm of these agents in COVID-19 patients. We also note that although we evaluated the relationship of the drug treatment regimens with the occurrence of ventricular arrhyth-mias, we did not measure QT intervals, nor did we stratify the arrhythmia pattern (such as torsade de pointes). We also did not establish if the association of increased risk of in-hospital death with use of the drug regimens is linked directly to their cardiovascular risk, nor did we conduct a drug dose-response analysis of the observed risks. Even if these limitations suggest a conservative interpretation of the findings, we believe that the absence of any observed benefit could still represent a reasonable explanation.In summary, this multinational, observational, real-world study of patients with COVID-19 requiring hospitalisation found that the use of a regimen con-taining hydroxychloroquine or chloroquine (with or without a macrolide) was associated with no evidence of benefit, but instead was associated with an increase in the risk of ventricular arrhythmias and a greater hazard for in-hospital death with COVID-19. These findings suggest that these drug regimens should not be used outside of clinical trials and urgent confirmation from randomised clinical trials is needed.
Here's the limitations section on the paper:
Source: https://www.thelancet.com/action/showPdf?pii=S0140-6736%2820%2931180-6