Phase 3 Coronavac study remains unpublished in scientific journal 1 year after preprint

A year since they were released on a pre-print platform, the results of Coronavac’s phase three study have yet to be officially published in a scientific journal.

The official publication, which goes through a process of peer review and editing, faced some difficulties to complete, including different methodologies developed by the Chinese pharmaceutical company, Sinovac, developer of the immunizer, and the research group in Brazil, led by the Butantan Institute. .

The departure of Ricardo Palacios, the institute’s former director of clinical trials and the study’s principal investigator, also delayed the release of the data. Now, infectologist Esper Kallás, who is also the last author of the study, hopes to complete the article and submit it for publication in the coming days.

In a note sent on the 19th, the Butantan Institute said that the data are being analyzed by researchers from Sinovac. In a new note, sent on the 28th, the institute stated that “there is no need for a study to be published and peer-reviewed before being sent to Anvisa for the definitive registration application”.

Anvisa (National Health Surveillance Agency) said that “the evaluation of the registration request depends on its presentation by the laboratory” and that “the fundamental thing is that it has access to raw and complete research data so that it can analyze the safety aspects and effectiveness”.

The dissemination of research results in an internationally recognized scientific journal is important, because only then can other scientists access the data, including supplementary material, and make an independent analysis of the results.

During the Covid pandemic, several scientific studies of vaccines began around the world. In 2020, there were more than 200 candidates and, at the end of that same year, about ten were in the final stages of human trials, that is, when thousands of people are evaluated to see if the vaccine is effective.

One of them was Coronavac, whose phase three clinical trial was conducted in Brazil with approximately 12,000 volunteers. Other smaller trials were also carried out in Turkey and Indonesia. Data from studies in the other two countries have already been published in international journals.

Despite having arrived at The Lancet’s preprints repository, researchers familiar with the study’s development told Sheet that the scientific journal rejected the article due to some unsatisfactory statistical analysis.

Kallás stated that the delay in publication is largely due to the rush and lack of time to complete the article, which is normal in a scientific process. The deadline for following up on participants (or when the database was “completed”) was July 2021, he said.

“Now it is necessary to do the final analysis and write the article. But the vaccine is good, I say this from the beginning, it is a great option, and it was thanks to it that Brazil reduced thousands of deaths from Covid in 2021”, he said.

In Brazil, effectiveness data (real-life effectiveness) of Coronavac were evaluated in a large study in Serrana, in the interior of São Paulo. Preliminary results pointed to a 95% reduction in deaths from Covid, 80% of symptomatic cases and 86% of hospitalizations when the municipality reached 95% of the vaccinated adult population.

Chile carried out mass vaccination first with Coronavac and then in conjunction with other immunizers. Data on the effectiveness of the immunizer in the country showed protection of 86.3% against deaths, 87.5% against hospitalizations and 90.3% against ICU hospitalization. The effectiveness against symptomatic Covid was 65.9%, similar to that found in the Brazilian study (62%).

Anvisa told the Sheet that the definitive registration is granted only if the laboratory makes the request and that Butantan has not done so until today.

People familiar with the definitive registration process at the agency said that Butantan did not apply for registration, as it did not obtain the in vitro neutralization data, which had been contracted by an external laboratory at the University of São Paulo.

The institute, however, said that Anvisa did not set any deadline for the delivery of the documentation, “but that it continues to work for the required data as soon as possible”.

He also stated that the contract with a USP laboratory to carry out the tests is for “services provided in other topics” and that the laboratory must be certified with biosafety level three, and that such laboratory does not have the certifications required by the agency.

The barriers to obtaining the definitive registration of Coronavac, whether scientific or bureaucratic, can, however, influence the continuity of the immunizer in the country.

Recently, the Minister of Health, Marcelo Queiroga, said that he will maintain the Coronavac recommendation only for children and adolescents aged 6 to 17 years after decreeing the end of the emergency character of the pandemic.

According to the minister, the ministry will make a request to Anvisa to maintain the conditional use authorization for another year of the vaccine for the pediatric public.

According to Anvisa, as published in a note, the agency requested a period of 15 working days for the necessary measures to be adopted to change the conditional use of immunizers with the end of the health emergency character of the pandemic.

Stock

Today, the state health departments have, together, 6,829,236 doses of the Coronavac vaccine in stock. The survey, with data collected by the Sheet until the 5th of this month, includes data from the 26 states and the Federal District.

Last month, the Butantan Institute, responsible for manufacturing the immunizing agent in the country, stated that, at the time, it had just over 350,000 doses and that they were being negotiated for export.

The number of doses of Coronavac ready in the country and available for use in children and adolescents aged 6 to 17 years may be even higher.

The São Paulo State Health Department stated that there are “more than one million” doses available for the application of the first and second dose in children aged 5 to 11 years.

Asked about the exact amount, the press office of the folder said that “the note sent previously is maintained” and did not provide the exact amount of doses.