The speed at which effective Covid-19 vaccines have come through to authorisation has caused surprise. Compared with previous vaccines, the process has been very fast and so, naturally, people are asking how can it have happened without some kind of compromise on standards and care. Explaining it all as simply a result of the wonders of the latest scientific advances seems vague. So how has it actually come about? In reality, there are at least 10 reasons: some are about good planning, some good science and some just good luck.
1. Pandemic plans were already in place
Long before the Covid-19 crisis, there was an awareness that a pandemic of some sort was likely in the coming years and plans had already been made to tackle it. Governments, international agencies and foundations had been pooling resources. The international Coalition for Epidemic Preparedness Innovations (CEPI) was launched in 2017, and when Covid-19 arrived they were ready. In addition, several companies and academic institutions, notably including BioNTech, Moderna and the University of Oxford, had also been working on new technologies capable of generating vaccines from the genetic codes of infectious pathogens and cancers, and testing them for several years.
2. China identified a novel coronavirus early on
Professor Yong-Zhen Zhang at Fudan University, Shanghai, and colleagues in China quickly obtained material from an early case of Covid-19 and identified a novel coronavirus. They elucidated the genetic sequence of the RNA in the virus very quickly and made the information public. That fired the starting gun for vaccine production. The fact that the RNA and viral vector vaccine platforms needed only the nucleotide sequence of the virus (the genetic code used by all living things from viruses to whales to reproduce themselves – in effect a series of letters you could send as a text message), and not a sample of the actual virus, allowed design and manufacture to happen very fast.
3. Substantial funding was granted immediately
The vaccine developers had access to immediate and substantial funding. Normally, getting money to develop new vaccines takes time: either you have to persuade grant-funding agencies or charities and their advisers – who are often your competitors – that your ideas are sound, or, if you are a company, you have to persuade your own directors or external funders to invest. With the health and economic costs of the pandemic so great, funders enabled all plausible options, while CEPI was also ready to support the most promising proposals immediately.
4. The clinical trials process was speeded up
The processes of writing clinical trial protocols and getting the necessary approvals to carry them out was speeded up. This usually evolves very slowly – ethics committees and regulators have to fit them into long queues of proposals. But this time researchers were working and meeting at all hours and extra personnel were drafted in. Committees received applications, prioritised them and made decisions usually within 24 hours. Everyone redoubled their efforts to put these studies first.
5. Vaccine trials started straightaway
Experienced vaccine teams were swiftly able to run Covid-19 vaccine trials. In the UK, there were already four centres ready to start the Oxford vaccine study immediately and, through the National Institute for Health Research, which coordinates all clinical trials done by the NHS, an additional 14 sites were identified and set up for the larger phase 2-3 studies that followed.
6. Research data was collected electronically
Information technology was readily available and made use of. Clinical trials have been slow to embrace electronic methods of data recording and collection for fear of glitches. Paper records are familiar, solid objects that everyone can see and believe in, but they are slow and error-prone. Where other sectors have led, research has now finally followed. When you buy an airline ticket, you do it online and the form does not allow you to make mistakes or omit important pieces of information before you complete a purchase. Such characteristics are also vital for data collection and, during the three to five years prior to this pandemic, research trials have been switching to this approach, with data collected straight into computers and tablets in the clinic. Mistakes and omissions are rare. Information is immediately available for analysis even as it is being collected.
7. Studies attracted a huge number of volunteers
There is massive public support for, and engagement with, these studies. Many people wanted to take part and help out. Typically, vaccine trials take weeks or months to recruit, but for these studies – assisted by the speed of media information, social media and the ability of subjects to register interest instantly online – it was possible to identify willing volunteers within just a few hours. Without the participants the studies could not happen.
8. Trials have yielded rapid results
For results, there need to be cases of disease. Even with all this speed, large-scale trials only got going towards the end or after the first wave of Covid-19 cases in most countries. While low rates of disease during the summer in many places was great news for our health, sanity and the economy, it actually made the trials more difficult. If you have large numbers of people who have had vaccine or control injections, in order to find out whether the vaccine works you need cases of Covid-19 to occur. You hope the cases will mostly be among the controls. But if no one gets sick you are none the wiser. The arrival of the second wave is a massive public health challenge, but it has enabled these trials to yield results rapidly.
9. Early vaccines worked well
It’s much quicker to get a result on a vaccine that works well than one that only works feebly. Even a vaccine that only prevents a small proportion of cases could be useful in the context of a pandemic, but it takes longer to find out whether a weaker effect is really there. If a vaccine were 100% effective (no such vaccine exists but just for the sake of argument) then you might only need about 20 cases of disease in your study – which would all occur among the controls – to be almost certain that the vaccine caused the imbalance of 20 sick controls and no sick vaccinated people. But if the vaccine was only moderately effective, 20 cases would not be nearly enough. Seven cases in vaccine recipients and 13 in controls could be due to vaccine-induced protection, but could also easily be chance and a vaccine having no effect at all. You would want many more cases – for example, 70 to 130 – to be more sure of your result. But getting 10 times more cases would take much longer. The fact that the early vaccines have worked well has made it quicker to be much more certain about the strength of their protective effects.
10. Regulation took place while the studies were continuing
Using “rolling review”, a completely different approach was taken to regulatory approval this time. Normally all the trial results and data are prepared in a massive package once the studies are finished, a process taking months. The whole lot is then presented to the regulators, which are the agencies that issue licences for drugs and vaccines, and they then begin their review, another process taking months. This time the data was provided to the regulatory agencies as they were being generated and was being reviewed while the studies were ongoing. When the final results came in, those were the only results left to be reviewed. The whole process took months, but the last steps took only days.
Authorisation is not the end of this “fast vaccines” story. Rollout and administration of vaccines began almost immediately. That isn’t normal either. No sensible company would start manufacturing vaccine until it knew it would definitely be allowed to sell it, but this time the manufacturing was done at risk and in advance. If the vaccines had failed, all of the doses already made would have had to have been scrapped. Fortunately, that has not happened.
There are more vaccines in the pipeline and we have more to learn about the ones that have arrived – much more information about safety and side-effects will accumulate as they are given to far larger numbers. But the fact we are already in a position to start protecting vulnerable and the highly exposed people by immunisation is the result of foresight, hard work and some lucky breaks.