Reply: Clinical studies on coronavirus disease 2019 (COVID-19) in the WHO registry network.

We would like to thank the authors for their knowledgeable comments on our study and for clarifying aspects of our methodology in relation to these concerns. We would also like to thank the author and his colleagues for their interest in our recently published paper “Current updates on the European and WHO registered clinical trials of coronavirus disease 2019 (COVID-19)” [1], and for taking the time to express their concerns.

The first concern was whether the observational studies are to be considered in the clinical trials concerning health care. As per the clinical trials definition (https://clinicaltrials.gov/ct2/aboutstudies/learn#Observational Studies), it has been suggested that in an observational study, investigators can assess health outcomes in different groups of participants according to a research plan. Further, participants may receive interventions (which can include medical products such as any drugs). For example, investigators may observe a group of older patients to know more about the effects of different medications on COVID-19 patients. However, as mentioned in our study, the maximum studies were in the recruiting phase, and there was no clear idea about the drug target for the treatment of COVID-19. This study includes two groups (Interventional or observational) for the comparison to get some idea about the effect of the different combinational drugs on the SARS-CoV-2. However, it is clear that the observational study is not in the clinical trial phase as shown in Table 1.

Table 1

Summery table of study selection and results obtained.

Clinical trials database	European Union clinical trial database + National Institute of Health clinical trials database
Status	Recruitment phase (n = 19), active phase (n = 4), completed (n = 2).
Drug used	hydroquinone alone or in combination with other drugs (n = 8), remdesivir (n = 6),Tocilizumab, Lopinavir/ritonavir either single or combined (n = 5), Interferon alpha and beta (n = 4), Plaquenil (n = 4).

The second concern stated in the letter was selecting the Clinical Trials Registry Platform for the study. In this perspective, we would like to mention that the primary goal of our study was to accumulate all currently ongoing clinical trial database results (EU and ClinicalTrials.gov), which has included a majority of the worldwide data in the clinical trial registry platform. However, we have selected only the three most extensive clinical trial platforms for the analysis.

There are several master protocols available in which multiple treatment options are evaluated concurrently in observational and interventional studies. This design provides flexible features such as dropping treatment options, declaring one or more drug treatments, or adding new treatments to be tested during the course of a trial [[2], [3], [4]].

In summary, we would like to thank the author for their concern regarding our article. We believe that our review is beneficial for the scientific community as we summarize the developments in clinical research during the current COVID-19 pandemic.

Conflicts of interest

The authors have declared that there are no conflicts of interest.