The plan to begin mass vaccination in early December 2020 will bring much needed hope for Christmas and the New Year. Pfizer/BioNTech has now received authorisation in the UK for the first COVID-19 vaccine produced in the western world. Moderna is likely to be next. It is a truly remarkable achievement that the pharma industry has transformed its drug discovery and development to launch vaccines in less than 12 months and deliver headline efficacy rates of circa 95%.

However, market authorisation is simply one leg in a relay race. The next stage will be managing the wave of information requests and safety reports that must be expected as part of the imminent COVID-19 mass vaccination campaigns.

Scale of the task at hand

Reports suggest that countries such as the USA and UK are aiming for 70% of their populations to be immunised by May 2021. That equates to ~47 million people in the UK, and with a two-dose vaccine this means on average 500,000 doses daily. Based on the initial clinical trial data shared for the two lead vaccines, 6-10% of subjects reported grade 3 ‘severe’ adverse events (defined as side effects that prevent daily activity) such as fever, fatigue, and headache.

For most marketed medicines, we know that people tend not report such side effects (often because it is rather unclear what they should do). The situation is different here, because of huge public health interest, the limitations of our knowledge all then fuelled by those who oppose any form of vaccination. Therefore, if just 1:100 people receiving the vaccine report a side effect, that means that for the UK alone there will be on average 25,000 reports per day with much higher peaks driven by vaccination rates and media activity.

 

UK

USA

Target population (millions)

47

230

Average number of vaccinations per day (2 dose)

>500,000

2,500,000

Number of people vaccinated per day

>250,000

1,250,000

Query / report rate

1%

1%

Number of safety reports per day

25,000

125,000

Table: Potential number of vaccine queries and reports per day

The need for public cooperation

For the mass vaccination strategy to succeed the public must be given confidence in the vaccines. They must understand the importance of returning for their second dose and be informed clearly and transparently about the potential side effects that may occur. Thus, there are three waves of information that must be shared between the manufacturer and healthcare professionals/the general public:

1. Information prior to getting the vaccination; people will want to know about what the vaccine might mean for them, should they take it if they have other conditions, if they are pregnant, if they have already had COVID-19, and what issues might arise after the vaccination.

2. Mid-flight information between the two doses; when do they need the second dose, why should they have the second dose, should they still go for the second vaccination appointment if they have a cold?

3. Post-vaccination information; what symptoms could they experience, what to do if they feel unwell, where to report a problem etc…

To achieve this, pharma must create a complete and true picture of safety as rapidly as possible. However, the numbers of queries and reports anticipated are orders of magnitude greater than the traditional capacity of pharma call centres. Many call centres are already struggling to operate at full capacity due to COVID-19 restrictions either because of staff sickness or because technology is unavailable to work effectively from home.

Vaccine inquiries may go to government websites or mobile apps (such as the Yellow Card system in the UK). This reduces the initial pressure on pharma’s reporting systems but introduces delay and can distort the medical content of the data as information is passed from government agencies to the relevant pharma company (and reverse) before undergoing full analysis.

Absence of proof is not proof of absence

Clinical trials are highly controlled experiments with highly selected subjects that are not designed to address ‘real world use’. Therefore, the boundaries of knowledge at the end of a trial are limited. In a general vaccination campaign, the range of age, background disease, smoking, alcohol, drugs of abuse, etc is wide, leading to a spectrum of efficacy and risk profiles of the vaccines across various sub-groups.

The earliest identification and mitigation of any, as yet unknown, serious reactions to the vaccine will be critical. In addition, we must track ‘unpleasant but not dangerous reactions’ that are likely immune responses to the vaccine (‘evidence its working’). Therefore, capturing the true spectrum of adverse events following vaccination is key. The most likely picture will be that side effects are relatively mild and serious adverse events are rare, however without data it is impossible for pharma or government agencies to determine whether severe or serious adverse events are associated with a vaccine or not.

In effect, reporting becomes an ever-improving circle of information; pharma communicate the known safety profile and side effects to the community at large, individuals report adverse events as they occur, pharma analyse the new information and update their communications accordingly thus optimising use and minimising risk.

Proactive and continuously updated advice to vaccinees will be key to mitigate adverse reactions, but also to maintain public trust and the integrity of the vaccination programmes. Industry cannot spend weeks waiting for the data and then weeks analysing it, data must be assessed with days or even hours because public trust is a stake. Given the speed and scale of vaccination, every day that data is unavailable for analysis, hundreds of thousands, or even of millions of people around the world could be exposed to a potential, preventable or manageable risk.  Failure to provide reassuring information that an adverse experience is a recognised immune reaction to vaccination will lead to individuals choosing to avoid their next dose, or worse, publicly fuelling further vaccine hesitancy.

Only through a system that proactively communicates with HCPs and the public, then collects and analyses their questions and problems in real-time and updates communication based on new insights will the people of the world go out and be vaccinated proactively.

Figure: Vaccine safety information cycle

Dr Andrew Rut is chief executive and founder of MyMeds&Me. He has deep expertise in pharmacovigilance and is a trained physician who has held senior roles spanning drug discovery and development within GSK working across USA, Europe, and Asia-Pacific.