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How does clinical research happen?

Find out about developments of studies for treatments of new coronavirus

12/06/2020 - 12h00
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Photo: Bruno Todeschini

In times of pandemic, the race against time for effective treatment against the new coronavirus is being addressed in different parts of the world. At PUCRS, dozens of researchers are working on different fronts for the fight, prevention and control of Covid-19. But, after all, how does clinical research happen? What needs to be taken into account to rank a study as safe and effective? 

The Dean of Research of Office of the Vice President for Research and Graduate Studies and Pharmacy researcher, Dr. Fernanda Morrone, explains that clinical research is defined by any investigation in human beings, aiming to discover or verify the pharmacodynamics, pharmacological and clinical effects as well as to identify adverse reactions to products under investigation in order to ascertain its safety and effectiveness. These analyzes may contribute to the registration or alteration of this product with the Agência Nacional de Vigilância Sanitária (Anvisa). 

Morrone and pharmacist Chaiane Zucchetti wrote about the profile of clinical research in Brazil and explained that the process of developing a new drug happens after a drug candidate is discovered. As it involves robust tests, the research aims to test molecular compounds; identify new targets and confirm their performance in the disease through pre-clinical research which is usually carried out first in vitro and then on animals. 

Focus on ethics  

According to the researchers, out of every 10,000 molecules analyzed, only one becomes a drug. “It is known that the process of innovation of drugs and medicines demands, besides time and resources, hundreds of millions of dollars and an average of 10 years of research”, Fernanda says. 

In the case of the new coronavirus, the Pharmacology Professor Dr. Maria Martha Campos, of the School of Health and Life Sciences, explains that there are alternatives for the development of drugs in situations like the one we are going through. “There is one development modality known as ‘accelerated’, as some steps can be advanced more quickly. This happens when there is no other therapy for a certain disease and the risk of death is high”, she explains. 

The study must be carried out in accordance with the ethical principles that originated in the Declaration of Helsinki. This declaration establishes ethical standards for conducting research involving human beings, based on their rights, safety and well-being. In Brazil, all clinical tests are being assessed by Institutional Review Board (CEP) of the institution where the research is carried out. If necessary, a second analysis by the National Research Ethics Commission (Conep) is carried out. The approval by Anvisa, through its Office of New Medicines, Research and Clinical Trials (GEPEC) is also necessary for research on medicines and health products that need authorization for import. 

Stages of Clinical Research  

The starting point is characterized by the discovery of a new molecule or selection of an existing molecule, followed by the preclinical phase. In this phase, in vitro tests and, then, in vivo tests take place, in order to verify if the molecule is safe enough to be tested on humans. With the approval of regulatory bodies, the new substance will be tested in a clinical environment in three test phases. 

Phase 1 will verify safety and efficacy; Phase 2 will assess efficacy and investigate side effects; and finally, Phase 3 will confirm efficacy and monitor adverse reactions. After the last phase, new reviews are carried out through clinical and preclinical findings. Only after phase 3 the product will be commercialized. Phase 4 is characterized by the marketing of the product under investigation and research on a new drug is continued even after approval. 

The team  

The structure of a clinical study requires a multidisciplinary team, consisting of a medical researcher, medical under-investigators, clinical study coordinators, patients, CEPs, sponsor, regulatory bodies of the Ministry of Health and the pharmaceutical industry or ORPCs.  

At PUCRS, Clinical Research Center (CPC), located at Hospital São Lucas, serves as one of the leading actors in conducting clinical research. The CPC, in addition to welcoming the researcher who will coordinate and conduct the research, is the link between the sponsoring industry, the CEPs and CONEP. The latter will provide the structure for the researcher, as it serves as the reference point of the research’s volunteer subject. 

The quest for solutions for Covid-19 

According to the most recent data published by Conep, an agency embraced by the Ministry of Health, the scientific community is joining efforts to carry out at least 76 studies with human beings to understand the behavior of Covid-19. Most of them (21) are working on clinical trials of possible treatments for the infection. The balance shows research with antibiotics, corticosteroids, convalescent plasma (from recovered patients) and even mesenchymal stem cells. 

For Maria Martha, in addition to the more accelerated research strategy, another possibility for clinical studies has been extensively explored for Covid-19. This is the case of testing drugs that are already on the market for the treatment of other diseases (such as chloroquine) or that have advanced in different stages of development for other viral diseases (such as Remdesevir), with possibilities of faster results. 

“This process is defined as repositioning of drugs, with wide dissemination. Obviously, pharmaceutical industries may be developing some new molecules for the treatment of Covid-19, and they have the right for patent protection and exploitation of the product. However, they must ensure that the product reaches all individuals affected by the disease and guarantee the production and distribution of the drug on a large scale”, the researcher explains. 

Information sharing also acts as an ally in the search for solutions. Interestingly, Maria Martha says that clinical studies for Covid-19 are registered in clinical.trials.gov (USA), allowing to evaluate the stages of the different tests. The best international scientific journals publish data from clinical studies on a regular basis. This is the case of the New England Journal of Medicine, which allows the entire community to constantly update progress in the fight against the new coronavirus. The largest search engine on biomedical topics, PubMed, is also providing a direct link to updates.