The British Scientific Journal British Medical Journal (BMJ) this week released a note in which it expresses its concerns about the study published in the company using an unprecedented dose of the drug proxalutamide in a patient with covid-19 in Brasília. The treatment was carried out by the endocrinologist Flávio Adsuara Cadegiani, without necessary ethical and scientific support. The demonstration took place after EL PAÍS brought the denunciation of the case in a report published on October 20th. In the same note, the BMJ reinforces the concerns raised by the National Health Council (CNS) regarding the experiment led by Cadegiani, which would have used 645 guinea pigs in three Brazilian states with the same drug. This may have led to the death of 200 people and would be “among the worst violations of medical ethics in Brazil”.
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According to the case published in the BMJ, which became a target of concern for the entity, a patient “in serious condition” of covid-19 received a dose of 600 milligrams of proxalutamide at Instituto Corpometria, Cadegiani’s private clinic in Brasília. The drug, which is studied for the treatment of cancer, is not registered in Brazil and was used by the physician without authorization from the National Health Surveillance Agency (Anvisa) and without meeting the basic requirements of the National Council for Research Ethics (CONEP). In addition, the dose used was higher than that recorded on any other relevant website for consulting scientific studies, such as Clinical Trials and Pub Med.
At the time, BMJ responded to the report that would investigate the case. The study is still published on the magazine’s website, but received a stamp called expression of concern, translated into Portuguese as a “statement of concern”. In it, the magazine informs that “Following the concerns raised by the BMJ, we are investigating the use of the drug reported in this case (proxalutamide) and the circumstances surrounding its availability and license for use. While the investigation takes place, we would like to alert readers to this expression of concern.”
The article released this November 17 by the British publication with the title Experimental trial of “covid-19 cure” is among the worst medical ethics violations in Brazilian history, regulators say it also draws attention to irregular research with proxalutamide in Brazil. The text cites not only the case of Brasília, brought by EL PAÍS, but also the research involving 645 people in Amazonas, Santa Catarina and Rio Grande do Sul, which is the target of accusations by CNS and CONEP.
“The clinical trial with proxalutamide ‘disrespects almost the entire protocol’ and may have contributed to the death of 200 people, reveals the CNS, the body that regulates clinical research in Brazil”, says the article. “The treatment was prescribed by physicians as if it were an established medical treatment, said the CNS, despite having been approved for clinical trials only. The number of people who received the drug was also greater than approved for the research”, he continues.
The BMJ nominally references the complaints pointed out by EL PAÍS. “The Spanish newspaper EL PAÍS reported that patients trusted their doctors to receive the best possible treatment and were not told that they were taking an experimental drug as part of a clinical trial. Some say the treatment was not followed up by the medical team. The consent form given to patients omitted important information about the entitlement of research participants and details about the study, the CNS said.” The BMJ reinforces the conclusion pointed out by the Council: “In the entire history of the Brazilian National Security Council, there has never been such disrespect for ethical guidelines and the rights of research participants”.
As Cadegiani was also not authorized to use the drug to treat a patient in his private clinic, the case also became the target of investigations by Anvisa. The Agency informed the report that “it identified discrepancies in the process of importing proxalutamide to Brazil and adopted some investigative measures that are ongoing.” However, it also states that “considering that the administrative investigation process is still ongoing — and that it is kept confidential — it is not possible to anticipate details in relation to the steps already carried out”. Flávio Cadegiani is also among the 80 suggested indictments in the CPI report on the Pandemic for a crime against humanity.
Carlos Gustavo Wambier, dermatologist and professor at Brown University, in the United States, also signed as responsible for the case denounced by EL PAÍS; Erica Lin, a medical student at Brown University; and Andy Goren, dermatologist and medical director of Applied Biology. Wambier and Cadegiani defended themselves by saying that the use of proxalutamide did not need Anvisa’s approval; that the 600mg dose was “probably ideal”, although unheard of; and that research with the drug was carried out without violating any ethical or procedural norms in the country. The version is contested by the main regulatory bodies for clinical studies in Brazil and, now, by the journal itself, which gave space to researchers.
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