On Monday, American pharmaceutical giant Pfizer and partner BioNTech announced interim analysis of late-stage trials of their coronavirus vaccine candidate. The company said early results showed that trial volunteers who received the vaccine experienced 90% fewer cases of symptomatic Covid-19 than volunteers who received a placebo. This data has not been published in a peer-reviewed medical journal.

How promising is this early data? In the event of regulators granting approval once the safety data was made available at the end of November, what are the problems in vaccine deployment we could encounter in India? Scroll.in spoke to medical scientist Dr Gagandeep Kang, professor of microbiology at CMC Vellore, known for her work on vaccines.

The first interim efficacy analysis of the clinical trial data by an outside panel of experts has shown, as per Pfizer’s statement, that the vaccine it is developing with BioNtech is more than 90% effective. Can you please explain this?
A large clinical trial is a blinded, controlled study with a proportion of people (volunteers) receiving the vaccine and a proportion of people receiving the placebo. The Pfizer study is a 1:1 randomisation, which means half the people in the trial get the vaccine, the other half don’t get it.

You then follow up and see who develops disease and who doesn’t. And you decide on what your limits of performance are going to be. How good do you want the vaccine to be?

In the case of Pfizer which has 44,000 trial volunteers, 22,000 get the vaccine and 22,000 the placebo. They get two doses each and then they are followed up to see who developed Covid-19, which means they must have a positive RT-PCR (molecular test to detect the presence of the coronavirus) as well as at least one symptom – that can been fever, loss of smell, loss of taste, shortness of breath, any one of these symptoms. This is the primary endpoint of the clinical trial.

In Pfizer’s case, they have calculated that they want a vaccine that has at least a 60% ability to reduce their primary endpoint (which is positive RT-PCR and one symptom).

Pfizer has calculated that they need 164 cases (that is, 164 of the 44,000 volunteers get Covid-19) for the total study but they also decided to do an interim analysis. These need to be planned in advance. Pfizer had earlier planned to do four interim analyses – one at 32 cases, second at 62 cases, the third at 92 cases and the fourth at 120 cases.

They have done this interim analysis now at 94 cases. And the vaccine is showing 90% efficacy.

Dr Gagandeep Kang.

Which means that most of the 94 Covid-19 cases occurred in the placebo group?
Yes. They have a total of 94 cases. They said eight people of those 94 Covid-19 cases had received the vaccine. That means 86 of them had not.

So this is very good news that this vaccine works but there are some important things to remember. First, is that vaccines always give you the most protection earliest after you start to measure efficacy. So the longer you continue to measure efficacy, the lower it could be. Because you just made your immune response and the virus hits you and you are able to fend it off really well. In vaccine trials it is known that shortly after immunisation is when you will see maximum protection.

In Pfizer’s case we know this is true, because the US FDA [United States Food and Drug Administration] has asked that any company that wants to submit a dossier has to provide at least two months of safety data after 50% of the participants are enrolled in the trial. So half the people have to be in the trial for at least two months.

Now Pfizer has finished enrolment but its two months median follow up period is going to be over only towards the end of November. Which means, what you are seeing is that early high protective effect in vaccinated volunteers and it is possible that the protective effect will go down once the trial runs for a longer period.

In the event that the Pfizer vaccine is given approval by regulators when the final data is in, what are the problems you anticipate in its deployment in India?
We have to remember that this is an mRNA vaccine (mRNA stands for messenger ribonucleic acids which translate DNA information into proteins involved in bodily functions). There are currently no licensed RNA vaccines. For India, RNA vaccines are going to be very expensive. Moderna has said that the cost of their vaccine is going to be US$37 per dose. I don’t know what Pfizer has decided its cost is going to be.

Also, this vaccine, right now, needs to be held (stored) at minus 80 degree Celsius. They are working on a formulation that will be more stable. But right now this vaccine needs to be at minus 80 degree Celsius. Currently we have no system in this country to be able to deliver a minus 80 degree Celsius vaccine. So, while it is good news – there is at least proof of principle that vaccines will work and will protect people against disease – there is also a long way to go.

(Reporter’s note: Research by German logistics firm DHL and consultancy firm McKinsey has found that insufficient “last mile” cooling facilities in the final delivery stages and a lack of storage at clinics in large parts of Africa, Asia and South America would “pose the biggest challenge” to delivering these vaccines at scale.)

There are several other vaccines that are in phase 3 trials. The WHO while welcoming the vaccine news from Pfizer has said that the world needs ‘several safe, effective and affordable vaccines to end this pandemic’. What are the main outcomes we are looking at for a SARS CoV2 vaccine?
The three things you look for in the performance of a vaccine are: Does it prevent infection? Does it prevent transmission? Does it prevent disease?

The primary outcome in this case [the Pfizer BioNTech vaccine] is that there should be a reduction in the number of people who have an RT-PCR positive and a symptom. So that is their primary outcome. Among those who have received the vaccine, there are fewer people who have an RT-PCR positive and a symptom. That is a clinical outcome. The vaccine is protecting against disease.

Is it protecting against severe disease? We don’t know that.

(Reporter’s note: Not everyone is protected from disease by immunisation. For example, it has been found that whooping cough vaccine lessens the severity of disease in those that catch it.)

Generally when a vaccine prevents disease, it does well against severe disease also. But until we see the results we can’t say.

Looking at prevention of clinical illness, however, is not the only thing we look for in terms of vaccine performance. We would like to know if the vaccine prevents people from getting infected at all.

That means that the people in the vaccine trial who have received the vaccine should not have an RT-PCR positive. Right now we are looking at RT-PCR and symptoms coming down, that doesn’t tell us whether there aren’t people that are RT-PCR positive but have no symptoms. That they got infected but they did not get sick. We want to know: does it prevent infection? Also, does it prevent transmission? Because it is possible that it may not prevent infection but it may prevent transmission, which is the viral shedding.