Kiran Mazumdar-Shaw Shaw spoke to Barkha Dutt, editor of Mojo, addressing doubts around India’s COVID-19 vaccines rollout, on whether India’s two approved vaccines are safe, what the difference is in the approval to the Serum Institute and Bharat Biotech vaccines and who should get the vaccines first. Here’s Part 1 of the interview.

Barkha Dutt: As someone who’s a woman in science have you been disturbed by the controversy around Covaxin vs Covishield, Bharat Biotech vs Serum Institute of India and for you are these 2 approved vaccines at par?

Kiran Mazumdar-Shaw: Let me answer this question in a different way. First and foremost, I think there needs to be a very articulate explanation of why there is this confusion in our society. I would like to start by saying that when we look at vaccines, what is it that we need to look for? Safety is paramount. I think immunogenic response is extremely important to access the efficacy of vaccines and ultimately you have to basically access efficacy and what do you mean by efficacy? Efficacy really means how long are you protected for? So, the debate we are having today, really revolves around efficacy because if you look at both these vaccines, both have demonstrated safety and immunogenicity of the desirable level. Now, if you look at the two vaccines, you can see that SII has actually conducted a bridging study on 1600 people to make sure that the safety and immunogenicity of the vaccines being developed in India matches with the safety and immunogenicity of the global vaccine that was developed by or manufactured or developed by AstraZeneca. Now, In terms of efficacy data, the SII is depending on the efficacy data provided by the global study done by AstraZeneca. The Global Study of AstraZeneca had various anomalies because they had conducted a faulty trial on a small cohort of patients which gave them 90% efficacy, then they took the efficacy data of a large trial which they had conducted in Brazil, South Africa and UK with the right kind of dosage and they got 62% efficacy and I think it was basically wrong for them to average the two and say it was 70% because that’s not the way to do it.

Barkha Dutt: That’s an important point. Can you please elaborate on that point a little bit? You’re saying that the efficacy of 70% that has been claimed by the Serum Institute vaccine is not correct because it’s the aggregate of two different kinds of doses?

Kiran Mazumdar-Shaw: So, the treatment regimen of one and a half doses for one which gave 90% efficacy and the treatment regimen of two full doses which gave 62% efficacy cannot be averaged into 70% by any kind of statistical means. I think you have to go with one or the other and in this case since most of the data is being looked at as the data provided by the larger study then you have to go by the 62% efficacy, which is fine, because it crosses the 50% efficacy threshold that the regulators around the world have agreed to and WHO has agreed to but the big question mark is – When you look at efficacy under normal circumstances, this efficacy is normally looked at for a period of one year at least. Now why do we do that? Because we want to know in a one year period how many people got re-infected and how many people remained protected. So when you are saying 50% efficacious, you are saying that 50% of the people remain protected and that is considered to be a pretty good threshold for any vaccine. Now when you say it’s 90% efficacious we are only talking about the four-week data. Over a period of four weeks, 90% of the people were protected by the Moderna and Pfizer vaccines. The efficacy was similar to the cohort of patients who got the one-and-a-half dose of the AstraZeneca vaccine; but 62% of patients got protected in the larger cohort that received the AstraZeneca vaccine. But we don’t know what these numbers will look like one year down the line. Will that 90% be reduced to 50% or will that 90% be reduced to 70% one year down the line.

Barkha Dutt: Can you explain what is efficacy in one line?

Kiran Mazumdar-Shaw: So, efficacy is the extent of protection of the vaccine in a population. So, if assuming that 100 people take a vaccine and if 50% of the people still remain protected which means they don’t get infected then it means it has 50% efficacy and that is a pretty large and acceptable level. So, what happens is today you are only focused on efficacy which certainly the AstraZeneca vaccine does have. At least, they provided 62% efficacy and combining that with the safety and immunogenicity data provided by Serum Institute the Indian regulator has taken a judgment call to approve this vaccine under emergency use.

Now comes the Bharat Biotech vaccine. The Bharat Biotech vaccine has shown immunogenicity and safety not just in the 800 people that were that came under the Phase I, Phase II but also 22,000 people who have received one dose and 3,000 people who have

received two doses. So, from a safety point of view, Covaxin is very safe. And as far as immunogenicity is concerned, they have actually demonstrated good immunogenicity in terms of neutralizing antibodies and T cell response in 800 subjects who went through the Phase I, Phase II trials. So, I think from the point of view of immunogenicity also the judgment call taken is that it has demonstrated good immunogenicity. So, the Subject Expert Committee would have basically extrapolated the data of neutralizing antibodies and T cell response, and concluded that the vaccine passes the 50% efficacy threshold, which is the minimum required efficacy level, in that four-week period. That’s the judgment call they made to approve this vaccine under an emergency use authorisation but they also introduced a caveat saying that since we really don’t have the efficacy data on the Covaxin vaccine, we would like you to give this to participants under what they called as a clinical setting which means that you need consent and you should follow up with those subjects. So the difference between the Serum Institute approval and the Bharat Biotech approval is that in the Serum Institute vaccine you don’t need to give consent, you don’t need to be followed up, you can just go and take your vaccine under the normal course whereas in the Bharat Biotech’s case you have to give consent which they will have to submit to the authorities and you will have to also make sure that you’re agreeable to be followed up.

Barkha Dutt: Okay you’ve given us a lot of information and what I want to do is break it down into very simple layperson language. So let’s first start with what you’ve said about efficacy, you are explaining that the efficacy of a vaccine in a normal situation, in peace time, would take a year so for any efficacy numbers that have been claimed by anybody Pfizer, Moderna, Serum Institute, Oxford-AstraZeneca, this we do not know whether it will actually hold for a year and efficacy quite simply is your odds of getting re-infected. In other words, you believe that the focus on efficacy is misplaced and not correct. Am I reading you right?

Kiran Mazumdar-Shaw: Well largely right because I’m saying that the numbers and the data we are looking at is for a very short period of time which is a four week period which is normally not done. So is that the right number is what I’m asking.

Barkha Dutt: The second thing you’ve said is that you believe that for Serum Institute and the Oxford-AstraZeneca vaccine to aggregate a half dose, on the one and a half dose model is wrong because these are two unconnected data points and therefore the 90% number is not something you’re comfortable with. You believe that they need to go back then to another trial to claim the 90% efficacy?

Kiran Mazumdar-Shaw: Yeah. So, I think US FDA has clearly said that if you want to establish that it is indeed 90% with one and a half doses, you’ll have to do a full trial. You can’t give me results of a 3,000-people trial and say that this is to be approved. They say you have to do a larger trial to convince us that this indeed is the proof of the hypothesis which you have demonstrated. Similarly, Europe is not willing to approve the vaccine based on the present trial data because they said you have not met any of the end points that you had started with and you have gone and changed your trial and now if you want to get full approval come with a clean set of data points.

Barkha Dutt: Now let’s come to Bharat Biotech where the maximum noise has been around the fact that no efficacy data was put in the public domain at all for phase III trials and people like Gagandeep Kang, very well-regarded scientist saying she would not take Covaxin because this is unprecedented. You’re disagreeing and you’re saying the focus on efficacy is wrong for this time for this situation?

Kiran Mazumdar-Shaw: No, my point is that look I think every regulator around the world is making judgment calls. These judgment calls are made on either extremely abbreviated pathways which are called warp speed pathways which is right because it is an unprecedented situation and there are others who are making judgment calls based on extrapolation like the Chinese have done, like the UK’s MHRA has done. They have taken a judgment call because they have had to basically do a post hoc analysis and go with that judgment saying okay we are willing to approve it. So, I think every regulator has made a judgment call on either Chinese vaccines or Russian vaccines and now even Indian vaccines. During an unprecedented public health emergency like this, you cannot fault any one regulator and call them out because all of them are trying to make judgment calls to protect their populations. We need to look at it in that way and as far as I am concerned if a vaccine has demonstrated immunogenicity based on neutralizing antibodies and T cell response; if a vaccine has demonstrated a pretty convincing safety data then I think you can be allowed to extrapolate and assume that you know it will cross the 50% efficacy threshold in that four-week period which they have agreed to. The Indian regulator has also insisted that Bharat Biotech’s Covaxin has to be delivered in a clinical trial setting. So that’s the caveat they’ve given and it’s up to anyone to decide whether they want that vaccine or not today. You must remember the vaccine is voluntary, it’s not mandatory.

Barkha Dutt: Are you comfortable with the clinical trial mode approval to Bharat Biotech?

Kiran Mazumdar-Shaw: Yes, I am fine with it because I think really at this point in time it’s not fair to make such judgment calls on any vaccine. For that matter, you can say that even the Serum Institute vaccine trial has been done on very few people in India. They are relying on a global set of data points and therefore I think there are so many contradictions in everything we are doing that I would go by the general kind of judgment that I would use for a vaccine of this type because there are so many unknowns and uncertainties so I would base my judgment on the immunogenicity and the safety data.

Therefore, I personally would take either of these vaccines. But the only challenge for people will be that if you are now going to be told that okay you can take the Bharat Biotech vaccine but you have to be followed up then people might say ‘I don’t want to be followed up, let me use the AstraZeneca vaccine.’ But I think the data from Bharat Biotech’s Covaxin on efficacy will also come very soon. So I’m sure that once that comes all these concerns and debates and discussions will be put aside because I am quite confident that it will pass the efficacy threshold.

Barkha Dutt: At the moment the main difference between the two again to summarize for you simply is that for one you can register, like provided you’re eligible and you’re in the first sort of set of people who can get it you can register and get the vaccine but for the Bharat Biotech vaccine because it’s a clinical trial mode I will have to fill in a consent form and then my case will be followed up.

Kiran Mazumdar-Shaw: Yes, correct and I would say that by the time you and I are eligible for the vaccine all the data that you need to know about efficacy will be out.

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