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This is how it is investigated whether a drug already in use produces an unexpected effect

With the vaccination of the covid-19 the international system of pharmacovigilance it is being tested like never before. “We are in an exceptional, unique situation, and we are watching very closely, almost in real time”Says an expert from the Spanish Agency for Medicines and Health Products (AEMPS), responsible for pharmacovigilance in Spain. At European level, the responsible body is the EMA.

The objective, they add in the AEMPS, is “to detect effects that cannot appear in the early stages of the trials, but only when a drug is administered to many people. Without pharmacovigilance we would have a false sense of security ”.

Previous trials have not failed

The appearance of an unexpected effect in an already approved drug does not imply a failure in previous clinical trials. There are variables that are impossible to contemplate even in the best designed trials.

There are effects that only emerge after a very long exposure or by the interaction with other drugs. Its incidence may be very low, as experts from the Spanish Association of Primary Care Pediatrics explain in a forum.

Rare effects, affecting one case in hundreds of thousands and beginning to show after millions of doses are inoculated, are only hunted by pharmacovigilance

As stated by the EMA, “patients may be taking other medicines, [o el efecto puede emerger] only when the drug has been used by a very large number of people or for a long time ”.

The rarer effects, for pharmacovigilance

The COVID-19 vaccines available in Europe have been tested with thousands of volunteers. They are trials that answer “questions about efficacy, and about the incidence of fairly common adverse events,” such as pain at the site of the puncture or headaches, he tells Nature. Hilda bastian, a contributor to Cochrane, a global network of researchers and clinicians that generates health information without commercial interest.

Rare effects, affecting one case in hundreds of thousands and beginning to show after millions of doses are inoculated, are only hunted by pharmacovigilance.

Temporal coincidence or causal relationship?

The great challenge of pharmacovigilance is to determine when an effect that coincides in time with the administration of the drug (days or weeks) is actually caused by it.

The process is open: in addition to health professionals, all citizens can report any event they consider suspicious

Pharmacovigilance begins when the drug goes on the market and lasts as long as it is in use. In 2007, the EMA’s European Network of Pharmacoepidemiology and Pharmacovigilance Centers was created. But the process is open to the general population: in addition to health professionals, all citizens can report any event they consider suspicious.

International databases

The notifications reach a large AEMPS database called FEDRA, connected to another in Europe, EudraVigilance. Spanish and European experts – from the European Committee for the Evaluation of Risks in Pharmacovigilance, the PRAC– analyze the information.

“This evaluation takes into account all the data available worldwide”, explains the AEMPS, and its recommendations “are applied in all the countries of the European Union”.

“All notifications are thoroughly analyzed,” they state in the AEMPS. It is reviewed in detail if there is other factors that may have caused the events and if the number of cases is greater than expected under normal conditions: “It must be taken into account that in the period in which a drug or vaccine is administered, other diseases do not disappear.”

In 2018, in two months, there were 205 hospital admissions for acute myocardial infarction per million inhabitants; 357 admissions for acute cerebrovascular disease; 77 admissions for asthma; 123 new cases of epilepsy or seizures; and 580 new cases of diabetes mellitus.

Alarms can go off if the frequency of a reported adverse event is higher than what is considered usual.

It is reviewed in detail if there are other factors that may have caused the events and if the number of cases is higher than expected under normal conditions.

Adverse event is not an adverse reaction

Expert analysis decides when a adverse event —The notification of a time match— becomes a adverse reaction —The drug is confirmed to be at its source.

Information on a confirmed adverse reaction should be included in the leaflet of the drug.

In addition, experts will try to discover the biological mechanism which triggers the adverse reaction, something that can take time.

This article was originally published on Expert voices, a section coordinated by SINC on the website of the Spanish vaccination strategy vaccinacovid.gob.es.

Rights: Creative Commons.

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