COVID-19 registries and drugs pipeline
However, clinical research is rapidly expanding and hundreds of clinical trials have been registered including, beside immunologic drugs, anti-viral drugs, protein-kinase inhibitors, anti-inflammatory drugs, or drugs aimed at facing the most severe symptoms of COVID-19, such as anti-coagulants, anti-infective drugs, drugs for the cardiovascular, respiratory and nervous systems (Table 2).
The WHO registryII (ICTRP) includes 1524 studies, whose details are not easily accessible. The registry, due to the heavy traffic generated by the COVID-19 outbreak is temporarily not accessible from outside the WHO.
US NIH Clinicaltrials.govIII lists 997 trials, including 617 interventional studies; only 14 of these trials have been completed, and the results have not been published yet.
EudraCTIV includes 131 clinical trials, which are still ongoing.
Cytel, Bill& Melinda Gates’ registryV lists 665 clinical trials, 322 from China and 102 dealing with traditional Chinese medicinal products. Most interventional studies evaluate the effects of hydroxychloroquine or chloroquine (147 studies), lopinavir/ritonavir (53 studies), plasma based therapy (35), and tocilizumab (26 studies). Only 7 of the 12 studies already completed with results (11 from China and 1 from France) have a randomized study design.
The conclusion of the registry for the two drugs more frequently investigated is that current data do not support the use of hydroxychloroquine/chloroquine for prophylaxis and treatment of COVID-19 and do not provide strong evidence about the efficacy of lopinavir/ritonavir in SARS CoV-2 infection.
In other registries the number of clinical trials ranges from 1480VII to 598IX.
The comparative review of registries allows some critical considerations.
There is a substantial discrepancy in the number of studies reported in different registries and it is quite difficult to identify duplicates among registries or studies listed in some registries but not in others.
Furthermore, the available information for individual studies differs from registry to registry and is not easily extractable. At last, protocols of studies are not accessible in most registries. Thus, it is highly appreciable the initiative of tracking and collating clinical trials in a single registry, also using artificial intelligence-based methods for data search and aggregator services18. This approach will make easier data sharing among investigators and analysis of pooled data.
Data sharing and secondary analysis represent valuable tools to advance knowledge and help regulatory decisions. Transparency policies have been recently adopted in Europe by the European Medicines Agency (EMA)19 in line with the new EU Clinical Trial Regulation20. Data sharing is also recommended by several international institutions21 and by the International Committee of Medical Journal Editors22. Data sharing appears fundamental in health emergencies, such as COVID-19 outbreak, to implement rapid and effective responses. Several platforms are available for data storage and analysis also offering protocol assistance and free anonymization of data from subjects with COVID-19IX.