When little information is offered on a topic that worries a lot, it is common for social networks to fill up, badly or well, the pothole, either with false information (fake news) or with real data that some actor – driven by personal interests – makes roll. The latter may explain why this Monday An internal ANMAT report circulates on Twitter dated December 23, precisely (confirmed Clarion, after checking the authenticity of the document) one of those who served as support for that body to “recommend” to the Ministry of Health to approve the use of the russian vaccine (Sputnik V) against the coronavirus, in people up to 60 years old.
It is a text signed by Nélida Agustina Bisio, technician of the Directorate of Evaluation and Registration of Medicines (DERM). In five pages, the technique informs its superior Marcelo Alberto Carignani, director of the National Institute of Medications (INAME), dependent on the ANMAT, the phase 3 intermediate data (collected until mid-December) that the Gamaleya Center presented to the Ministry of Health of the Russian Federation.
It follows that, as it is not a minor document, Bisio copied two heads of Carignani himself: Manuel Limeres and Valeria Teresa Garay, no less than those who occupy the second and third positions in the ANMAT line of command, headed, from now on, by the Minister of Health of the Nation, Ginés González García.
The study in question is a cut (or endpoint) that had already been advanced by Clarín: they are 12,296 volunteers from 18 to 87 years old, part of the 40,000 that includes phase 3 of the Sputnik V vaccine. As is known, beyond the fact that vaccination in Argentina will begin this Tuesday, the data in this document (until now, confidential) were not published in any journal scientific, something that would happen in January.
What does the report say? At least three important things. The first, that the effectiveness of the vaccine is higher than 91.4% deduced from phase 2, and that it would reach the 96%.
The second, that the data provided in relation to those over 60 are “lazy”. That is why the technicians in charge of the report explain that “based on these data for people over 60 years of age, it is recommended to wait the report of more data on efficacy, immunogenicity and safety ”.
The third, that there was 12 adverse events considered “serious”, of which 3 occurred in people over 60 who had received the vaccine: a case of renal colic, another of deep vein thrombosis and a “limb abscess”.
On the other hand, the “Security Analysis” reports 8,704 mild adverse events in 4,401 volunteers. The most frequent observed “was flu-like syndrome in people who received the vaccine compared to placebo,” the report says.
Points of view
Two renowned scientists, Andrea Gamarnik, a virologist at IIBBA-Conicet, who led the development of the famous COVIDAR IgG serological test, and Juliana Cassataro, who from UNSAM heads the preclinical research of what could be the first vaccine against the coronavirus in Latin America, put cold cloths on the question of adverse effects.
According to Gamarnik, “the results are very encouraging in relation to the efficacy of the vaccine. In relation to the adverse effects of the 12 cases, the other vaccines have also reported adverse effects. The most important thing is that based on the information available, the regulatory authority, that is, ANMAT, indicates that the results are satisfactory. “
Cassataro, after objecting to the request to offer an opinion on a document not officially communicated, considered that “they do not seem to be events considered warning signs and they do not seem to be related to the vaccine. That is why they are not considered relevant.”
The experts highlighted that emergency use is altering the approval mechanisms of all vaccines. They exemplified with Moderna’s vaccine, “approved in the United States without any published phase 3 paper,” or that of Pfizer, approved in England and Canada a week before accurate results of that phase are published.
Different is the opinion of Adolfo Rubinstein, former Minister of Health, Doctor of Medicine and Master of Clinical Epidemiology, who opined that “the paper may not have been published; that is not the issue. Of course, it would be better if it was published, but Moderna’s vaccine, for example, that It does not have a published paper, it submitted data to the FDA and it is a long dossier of about 60 pages, with detailed results that are public. It is public and transparent information. “
Regarding the document that circulated this Monday, Rubinstein was critical: “The study does not have statistical power to detect important differences in the number of adverse effects. And I could not tell you if you have to worry because there are few events and the ratio of those who received placebo and vaccine “.
“In addition, the relationship between those who received the vaccine and those who received placebo is three to one. If we add to this that, as the Russians said, they are going to vaccinate the placebo group, they will be left without a control group to do adequate follow-up. There are methodological problems with this study, “he said.
A double-blind trial assumes that half of the volunteers receive the drug they are trying to test, and the other half, placebo (that is, nothing), with no idea – neither the participants nor those responsible for the study – who received what. Before starting the test, it is defined at which points (or endpoints) partial data will be opened, to do a careful follow-up of the investigation.
In this case, it had been determined that with “at least 20” Covid-19 infections a portion of the data would be revealed. That is why the report explains that “they were verified, at the time of the database closing and have been included in the primary efficacy analysis, 12,296 subjects and 27 cases of Covid-19 according to what was planned for the first interim analysis cut-off point (at least 20 cases) ”.
As evaluated, “the population included in the two arms of the study did not show statistically significant differences in relation to the variables of age, sex, weight or race”, and they deduce “An acceptable safety profile” of the Russian vaccine.
An important fact (but of which not many details are given) that is several of the participants had comorbidities: almost 26% of the volunteers in the “vaccine” group, and 27.3% in the “placebo” group.
As for those over 60 years of age, although Russia announced this weekend that it finally approved the emergency use of Sputnik V for that age group, the authorization given by the Argentine Ministry of Health does not include, for now, that age group. population. And, in fact, the ANMAT internal report justifies it.
The argument is concessive, yes, but also cautious.
First, they explain that “a statistically significant difference is not observed (in terms of efficacy, compared with those under 60 years of age) in those over 60 years of age, which could be due to the low incidence of cases registered at the time of cut-off.”
Then, they add: “The safety profile in people over 60 years of age did not differ from the safety profile observed in the rest of the population analyzed. Considering that 1,029 subjects over 60 years were exposed to the product under investigation, a new safety analysis is suggested while waiting for adverse events that could be observed in a greater number of exposed subjects ”.
And a third paragraph clarifies that “the analyzed report does not yield data in relation to immunogenicity in people over 60 years old”, from which it follows that “based on these data for people over 60 years old, it is recommended to wait for the report of more efficacy, immunogenicity and safety data ”.