**4. Discussion**

Many clinical trials related to the COVID-19 pandemic have emerged in response to society's concerns related to the impacts of the pandemic, and in response to this global emergency. Scientific production on the topic is dynamic and fast, which makes the sharing and synthesis of knowledge important [15]. In this context, the characterization of research efforts can help professionals, researchers, and managers to understand the relevant aspects of the disease.

Considering the serious public health crisis of COVID-19 and the search for discovering safe and effective treatments, high-quality research is needed to evaluate interventions for the prevention of the disease and its treatment. Clinical trials properly designed and conducted make their results valid and can significantly contribute to the effort to improve the effectiveness and efficiency of health interventions [21].

"Clinical Trials" is a robust platform for registering clinical trials, containing detailed information on a large amount of clinical research conducted in 219 countries [22]. According to the Dimensions database, "Clinical Trials" is the leading platform for registering clinical trials on COVID-19, accounting for 58.8% of all registrations [23]. Of the clinical trials registered and found on this platform, a significant number is being developed by American researchers. This research leadership is underpinned by huge public funding, mainly from the National Institutes of Health (NIH), which has already received more than US\$ 3.6 billion to fund research on COVID-19 [24], as well as from government agencies, universities and the private sector [25], which demonstrates the urgency of the USA in the face of the severity with which the disease reached the country [18].

Among studies analyzed, the majority of participants are adults and older adults. It is known that COVID-19 is less prevalent in children compared to adults and adolescents and that younger individuals infected with SARS-CoV-2 have less severe symptoms and lower hospitalization and lethality rates [26, 27]. In March 31, 2021, 11.7% of COVID-19 cases in the United States were of children and adolescents up to 17 years of age, corresponding to almost 3 million cases. Of these, for the age group of 0–4 years, there were only 104 deaths (<0.01%) and, for the age group of 5–17 years, only 228 deaths (0.1%) [27]. Therefore, these may be the reasons for choosing the age group of adults and older adults.

The most frequent study design was randomized allocation, the parallel intervention model and the open masking type. The randomization of a clinical trial ensures that, in addition to intervention, there are no systematic differences between study groups, providing impartial results regarding the effect of interventions and reducing biases [18, 28]. Even so, only randomization does not exclude the possibility of systematic differences, because since those involved in a clinical trial are aware of the attributions of interventions, which can influence the result and introduce bias [29]. In our study, masking was not feasible mainly for ethical reasons or because patients are incorporated into healthcare environments, making it difficult to blind the team that manages patient care [30].

There were greater number of clinical trials for therapeutic purposes that evaluate some drug as a type of intervention. These results may be related to the current world scenario and the urgent need for studies analyzing which treatments are shown to be most effective against COVID-19 [18] in an adequate and quick manner. The discovery of an efficient therapy would allow the prophylaxis of health professionals who are on front lines, so that they could get back to work more quickly, in addition to reducing the time spent by critically ill patients in intensive care units, freeing beds [31] and reducing mortality rates. Many studies using a placebo group were also found, and due to the lack of approved available treatment, this procedure is ethically acceptable [18].

In this study, the most frequent sponsors were pharmaceutical/biotechnology companies and universities. However, in the evaluated clinical trials, there was the collaboration of several companies, academic institutions, government agencies, non-profit organizations and individual medical researchers to properly implement resources in the fight against COVID-19 in order to concentrate and accelerate the development and implementation of therapies. This partnership of efforts may reflect the so-called Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV), conducted by NIH and announced in April 2020, in which researchers continue to work intensively to develop new and better treatments [32].

Regarding the classification of many tested drugs, biological interventions, dietary supplements, combined products and some other types of intervention, heterogeneity of classes used can be observed. Most clinical trials have been evaluated immunosuppressants or combinations of antivirals/immunosuppressants, some already with USA issued by the FDA and redirected for the treatment of COVID-19, such as the combination of immunosuppressant Baricitinib – used to treat rheumatological diseases [33] – with antiviral Remdesivir – used to treat patients infected with the Ebola virus, MERS-CoV and SARS-CoV-1 [34], and its use as monotherapy for certain patients hospitalized with COVID-19.

Other authorized drugs that deserve mention are the biological products Bamlanivimab and Etesevimab – neutralizing IgG1 monoclonal antibodies that bind to different but overlapping epitopes in the binding domain to the SARS-CoV-2 spike protein [35] –, REGEN-COV (Casirivimab and Imdevimab) – neutralizing recombinant human IgG1 monoclonal antibodies that target the binding domain to the SARS-CoV-2 spike protein receptor [36] –, and the COVID-19 convalescent plasma – collected from individuals whose plasma contains anti-SARS-CoV-2 antibodies [37].

The COVID-19 pathogenesis begins with the replication of SARS-CoV-2, subsequently followed by an exaggerated immune /inflammatory response to the virus that leads to tissue damage. Regarding this knowledge, it is assumed that antiviral therapies would have greater effect early in the course of the disease, whereas immunosuppressive/anti-inflammatory therapies may be more beneficial in later stages of COVID-19 [33]. The use of these existing drugs helps reducing the cost and time of research; however, further large-scale studies must be carried out to assess the benefits and safety of these drugs.

The findings reported here make it clear that researchers from different fields of medicine have worked together in the development and clinical evaluation of several drugs aimed at treating the numerous medical complications caused by COVID-19. Extensive financial resources, made available by universities and pharmaceutical and biotechnology companies, have been applied in order to allow the conduction of clinical trials with high methodological and scientific rigor for both diagnostic and treatment purposes. Undeniably, the emergency approval of the tested drugs described here by the FDA, while making it possible to save thousands of lives in the American territory, has allowed a better understanding of their effects on individuals affected by COVID-19, which knowledge has been shared and put into practice by managers and medical teams from various countries around the world.

Therefore, during the COVID-19 pandemic and due to all resulting restrictions and difficult circumstances, good scientific practice and data transparency are essential principles that should guide the conduction of clinical trials. The sharing of these results, when properly carried out, helps professionals to make decisions, as well as researchers to identify gaps and more promising interventions, to avoid research waste and to expose patients to unnecessary risks, consequently contributing to the advancement of scientific knowledge.

*Clinical Trials on COVID-19: What is Being Researched in the United States? DOI: http://dx.doi.org/10.5772/intechopen.98494*
