Side effects: under what conditions will the anti-covid vaccine be authorized?

In the global race for vaccines against the coronavirus, ten projects have reached phase III of clinical trials, the last stage before obtaining or not obtaining validation from the health authorities, but what are the criteria likely to tip the balance?

An "early 2021" antidote available in the EU? The announcement by pharmaceutical group Pfizer that its vaccine against Covid-19 reduced the risk of contracting the disease by 90% immediately sparked a wave of optimism, although it is not yet unclear whether it confers immunity. long. However, this deadline remains conditional on a crucial step before any product of this nature is placed on the market: validation by the health authorities, ie the European Medicines Agency (EMA) in this specific case.

Effectiveness, side effects, number of volunteers ... what are the criteria that will condition this green light? Do they differ from the usual approval process given the huge current health issue? Who are those who are likely to tip the scales one way or the other?

Safety and efficacy criteria

“Overall, there is no reason why the validation criteria should be different for this vaccine versus what is usually examined for any other drug”, underlines Dominique Deplanque, professor of medical pharmacology and director. of the Clinical Investigation Center of the Lille University Hospital. The certification that allows a drug to be marketed "is always issued according to criteria of safety and efficacy," he recalls. In practice, the authorities examine all the data resulting from the tests and experiments which have been carried out and then transmitted by the laboratory which develops the drugs or vaccines concerned.

"The safety aspect concerns taking into account the most benign as well as the most serious adverse effects", explains the specialist, referring to the classic influenza-like illnesses which can accompany any vaccination, as well as "rarer pictures, in particular neurological, and which only occur if a large number of subjects are administered the product. " With regard to the efficacy assessed by the competent authorities, it consists in highlighting a benefit / risk ratio. "In other words, what do we think the vaccine in question makes it possible to reduce the probability of being infected, of manifesting even mild symptoms, or of developing a serious form of the disease", summarizes Professor Dominique Deplanque .

"A number of subjects treated without common measure"

The evaluation of these criteria therefore applies to Covid-19 vaccine candidates, in the same way as any other vaccine or drug. However, the validation by the European Medicines Agency (EMA) of a future anti-Covid 19 vaccine will indeed have an unprecedented dimension, like the context. "The number of subjects treated by this future vaccine will be beyond comparison with any drug put on the market over the past five years," he recalls. "This is purely statistical, the greater the number of subjects to receive the drug, the more the probability of seeing a serious and rare effect appear and in the case of the vaccine against the Covid, the figure can become significant" points - he, stressing "the need to remain very vigilant concerning the possible occurrence of adverse effects". According to him, it is obvious that this parameter will lead to a "certain caution" of the health authorities during the validation procedure, but also subsequently, "in real conditions of use". Even if it means calling into question the placing on the market.

"In terms of adverse effects, there are no figures or predefined threshold not to cross, what prevails is always the observation of this difference between the benefit and the risk", insists- he. And to popularize: "we do not accept the same adverse effects in the case of treatment against cancer and that of a cold, for example".

Additional studies in case of doubt

If there is any doubt about this benefit / risk balance during the validation procedure, "the authorities may have to request additional studies on sub-populations," he explains. It is also not excluded, given what we know about the virus, that "the evaluation of the effectiveness of a vaccine against Covid is differentiated according to the population profile due to any specific effects observed in elderly or obese patients. " Consequently, "to avoid any risk, the authorities could in fact decide that such and such a vaccine could be administered to such and such a population and not another".

Note that to speed up this approval phase, the Committee for Medicinal Products for Human Use (CHMP) within the EMA is already examining Pfizer's results, with validation therefore taking place throughout the process. tests followed and not after, as usual. This accelerated review procedure, called "rolling reviews", is intended to save precious time in the vaccine validation process. By way of illustration, it is thanks to the latter that the experimental antiviral Remdesivir was able to obtain its marketing authorization in June.

After obtaining this marketing authorization, it will be for the French authorities to define the vaccine strategy, namely "who should be vaccinated as a priority given the efficacy rate of the vaccine".