Beyond the finish line

Scale of the task at hand

Reports suggest that countries such as the US and UK are aiming for 70% of their populations to be immunised by May 2021. That equates to ~47million 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 to 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. In addition, the move by government health bodies to extend intervals between doses (in a bid to increase the number of individuals with a level of immunity) is likely to drive many questions and concerns in the general public. Therefore, if just 1:100 vaccine dose recipients make a query or report a side effect, for the US alone there will be on average 25,000 reports per day, with much higher peaks driven by vaccination rates and media activity (See Figure 1).

Figure 1: Potential number of vaccine inquiries 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…

Absence of proof is not proof of absence

Clinical trials are highly controlled experiments with relatively small numbers of highly selected subjects, limited doses and dosing ranges with a short follow-up period. Therefore, the boundaries of knowledge at the end of a trial are limited and not reflective of real-world use. 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 subgroups.

Capturing the true spectrum of adverse events following vaccination is key. The earliest identification and mitigation of any, as yet unknown, serious reactions to the vaccine will be critical. In addition, those reactions that are ‘unpleasant but not dangerous’ and likely the result of immune responses to the vaccine must be tracked.

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 communicates the known safety profile and side effects to the community at large, individuals report adverse events as they occur, pharma analyses the new information and updates its communications accordingly thus optimising use and minimising risk (see Figure 2).

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 within days or even hours because public trust is at stake. Given the speed and scale of vaccination, every day that data is unavailable for analysis, hundreds of thousands, or even 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 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.

Dr Andrew Rut is chief executive and founder of MyMeds&Me. He is a trained physician specialising in Endocrinology and Genetics. He has held senior roles spanning drug discovery and development within GSK, including head of Safety

Figure 2. Vaccine safety information cycle

Dr Andrew Rut is chief executive and founder of MyMeds&Me. He is a trained physician specialising in Endocrinology and Genetics. He has held senior roles spanning drug discovery and development within GSK, including head of Safety