Pharmacovigilance at work

Europe, and possibly the whole world, are holding their breath for the conclusions of the Pharmacovigilance Risk Assessment Committee (part of the European Medicines Agency) on the AstraZeneca COVID-19 vaccine immune thrombocytopenia safety signal.

The committee has already produced some preliminary pronouncements on their 8-11 March meeting: “there is currently no indication that vaccination has caused these conditions, that are not listed as side effects with this vaccine”. However, due to further thrombosis cases from the weekend and the subsequent AstraZeneca vaccine suspension from many European governments, an emergency meeting will be held on 18 March 2021.

So far PRAC pharmacovigilance activities were being carried on as usual: even the BioNTech/Pfizer and Moderna vaccines are being scrutinized with respect to immune thrombocytopenia and there are also other safety signals, such as anaphylactic reactions and swelling, that are being analyzed. All in all, even though public attention on the matter is justifiably high, the extraordinary COVID-19 vaccines rollout was close to business as usual. And yet, a growing unease around the AstraZeneca vaccine grew to the point that even the European institutions couldn’t ignore it. How could this happen?

Original sin

The AstraZeneca ChAdOx1-S COVID-19 vaccine was the third of his kind to be approved by the regulatory authorities around the world. However, this seemingly excellent scientific result was immediately perceived as a burning business defeat: thanks to an amazing technical leap, BioNTech/Pfizer and Moderna developed vaccines that were more effective with less time and money. The pressure on AstraZeneca’s executives was tremendous.

Already behind in this rush for public coverage, AstraZeneca declared that their vaccine had an efficacy of 90% with a specific dosing regimen (half-dose first, standard dose later). However this turned out to be an ephimeral result: the half-dose regimen was not included in the study protocol, rather it was an accidental discovery due to operational errors in the study conduct. As you surely know, the canonical experimental method (clinical trials, after all, are experiments) is based on the following steps:

• formulate a hypothesis;
• devise and conduct an experiment to answer this question;
• gather the results, that may contradict or confirm the initial hyphotesis.

Accidental findings, such as the half-dose regimen efficacy, should therefore be subject to their own experiments, prior to be assumed as “science”.

Now, I can only speculate on the temptation that led AstraZeneca executives to orchestrate a communication campaign that at first omitted the circumstances of the half-dose regimen finding. Even though they would be still behind in terms of timing and return of investment, they could at least match their competitors in terms of efficacy. Except, the half-dose regimen claims didn’t hold up to further investigation. As of today, the AstraZeneca COVID-19 vaccines is used with the two standard doses regimen and the illusion of the half-dose miracle left the place to public doubt on the company.

Moreover, as AstraZeneca clinical trial was being analyzed by regulatory authorities, doubts were also cast on the coverage of over-65 years old subjects, by far the most vulnerable to COVID-19. Only lately this vaccine is being authorized for this category of people.

A lesson in earnestness

As Robert B. Cialdini explains in his “Pre-suasion” book, persuasion is way more effective with the support of deliberate prior ground work. However, it also goes the other way: the shady half-dose ruse, together with the initial lack of data on elderly people (was it deliberate? See how this “chain of doubt” works?), built up to the present day AstraZeneca PR disaster. No matter how you look at it, a simple temporal correlation with a handful thrombosis cases over several million subjects was amplified to the point of a major health scare.

From this sorry state of things we can still draw an invaluable business lesson: think for the average/long term, be earnest, and be resilient. No matter how alluring a shortcut may look, reject it. At least do it to avoid bearing the weight of public contempt for the time being.