Decoding India’s Covid Vaccine Approvals with Kiran Mazumdar-Shaw: Part II

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 2 of the interview.

Barkha: Are you concerned because you started by saying that there should have been better articulation of all of this. Now what’s happening is that anti-vaxxers, rumor mongers and conspiracy theorists are going to step into this space. You do not believe the regulator has made a mistake but perhaps the one mistake he did make was to not take questions, if he had taken questions at his press conference maybe this confusion would not have risen, point one. Point two, when ordinary Indians hear Dr Krishna Ella of Bharat Biotech saying paracetamol was given in the AstraZeneca trial and they hear Adar Poonawala saying that Bharat Biotech is safe but just safe like water. What do ordinary Indians make of this?

KMS: I think that was unnecessary. I don’t think such comments should have been made and I really think that the drug regulator the DCGI ought to have taken some questions to clarify some of these concerns and all this could have been prevented. So I’m very sad that this has come to this kind of a controversy. It should not have been. It should have been a proud moment for India that two vaccines have been approved and that people are feeling elated and confident now there may be a return to normalcy soon. Even though it’s unfortunate all this has happened, we need to now move on.

Barkha: I think they’re trying to do that with their joint statement as well. So, let’s actually start taking a few questions that are coming on our screens that are about the science and that’s what really matters at the moment.

Assuming some of the recipients are given Covaxin before the phase III trials efficacy data comes out and subsequently if the trial results show a low efficacy say it’s below 50% will they be vaccinated with other vaccines then?

KMS: Well, they can certainly be re-vaccinated with other vaccines. So let’s not assume these kinds of things but certainly I just want you to know that the difference between adenoviral vector vaccines and Bharat Biotech’s whole-virion inactivated COVID-19 vaccine is that once you’re vaccinated with an adenoviral vector vaccine and supposing that does not pan out in terms of durability of response then you cannot take another adenoviral vector vaccine. You will have to actually take the Bharat Biotech vaccine but yes if the Bharat Biotech vaccine fails you can certainly take an adenoviral vector vaccine. In fact, if you know, in the UK they have even come up with another model where they are saying you can mix and match vaccines and you can also maybe take the AstraZeneca vaccine after three months and of course US FDA is absolutely not agreeing with this. So, you can see how each regulator is making judgment calls. Some of it definitely stands to good scientific reasoning but the debate we’re having right now is not about just the scientific reasoning, we are having this big debate on clinical trial protocols. So, there is a big difference between saying have you followed protocol or are you using scientific judgment. I think that’s where the real debate is and I for one would say let’s follow the science. I think if you follow the science a lot of answers can be found.

Barkha: Is efficacy of a vaccine based on illness or infection? Disease or infection?

KMS: Efficacy right now is based on infection; the way efficacy is assessed is based on infection but obviously that infection leads to illness if it is severe. Each company today is measuring efficacy in its own way. Moderna and Pfizer are only testing symptomatic patients for Covid-19 and they are reporting 90% based on the symptomatic patients who have

tested positive or negative. Whereas AstraZeneca is doing the right thing as they are testing both asymptomatic and symptomatic people. Every two weeks they are putting all their people on a RT PCR test and they are reporting all people who have tested positive and they are testing it over a four-week period. So, when you say that efficacy is 62% it means that the 38% people both asymptomatic and symptomatic tested positive in that cohort. So, they look at the number of people who tested positive. The people who tested positive are put into one cohort and you see how many of them are on placebo and how many are on the actual dosage, the vaccine. So, when you say 62% efficacy, it means that there was a cohort of say for example 100 people who tested positive out of which 62 people were on the vaccine arm and 38 people were on the placebo arm. That’s how you say 62% efficacy.

Barkha: But the question still remains is that the vaccines are safe but they may not be effective?

KMS: There is one more caveat that I want to add to that is what they found in the AstraZeneca study and many other cases is that even if people have tested positive nobody went to the hospital, so even if they tested positive in the RT-PCR test these people never went to the hospital which means they all had very mild cases of COVID-19 which were completely resolved in a short time.

Barkha: We know that these vaccines are safe, that they have shown positive results on immunogenicity, but we do not yet know how effective they are or how long lasting they are in their efficacy which means we don’t know if we will need this vaccine every three months, every year or how often we will need this vaccine?

KMS: We don’t know that. We have no idea whether it will last for three months, six months, nine months or a year or forever. So, until time passes, and we get more data you won’t know how long these will last. Look at the efficacy data for four weeks. Is that a number we are really comfortable with? Don’t you want to be protected more than four weeks?

Barkha: Today, which of the four vaccines would you take?

KMS: I think with no known data on durability of response every vaccine is fine. What I am trying to say is that today AstraZeneca is also saying that by the way when you take my first dose you can be protected for three months; we can then give you the second dose after three months, but these are all anecdotal kind of interpretations based on cohorts and subset analysis. So unless you do a proper trial you really don’t know what is the durability of response.

Barkha: So, I think we’ve understood a lot at least I have for the first time understood what the efficacy of a vaccine actually is? I want to move to who should get the vaccine? Because you’re basically saying at the moment a lot of people may choose the AstraZeneca vaccine over the Bharat Biotech vaccine for one reason alone that Bharat Biotech at the moment requires a consent form and a follow-up. Also, that could change. It could change in a few weeks, it could change in a couple of months once the efficacy data of the Phase III trials on the Bharat Biotech vaccine has been presented. So that I’ve understood. Now let’s come to how the rollout should happen and I know that you have some sort of deeply thought views on this, some unconventional views on this that are challenging some of the assumptions. Let’s come to the key question: other than health workers and frontline workers, that’s a no-brainer, who should be in line to get this vaccine?

KMS: So you know, the conventional thinking is that you need to stratify the population based on who we think needs the vaccine first which as you mentioned are the health-care workers, the essential workers, the elderly, the people with co-morbidities. It makes a lot of logical sense but then the question I want to ask you is that look you have to give two doses, so essentially and effectively you are not really protected between the two doses. So, if an elderly person who stays at home and in India most elderly people are sedentary. They don’t keep going out to parties or socialise much. So, these elderly people generally are very sedentary and supposing they get their first dose but they are staying with family members and young people who have not been vaccinated. Now don’t you think they are the ones who can actually infect this elderly person if they don’t get vaccinated themselves. So, it does not make sense to just vaccinate one member in the family and not vaccinate the others in the family. That to me is the first illogical way of approaching it. Secondly, the announcement that we will open up schools but we need to make sure that the teachers are vaccinated and the parents are vaccinated. Now how are you going to then justify that all school going children’s parents will be vaccinated even if they are not in the priority category, but others will not be allowed to be vaccinated. I mean it’s a bit of a mishmash and then if you say schools can open then you will say even colleges can open, then the college will say their students will have to be vaccinated. We’ve already seen that even in a country like America where they were supposed to vaccinate 20 million people in December they were only able to vaccinate 2 million which means 10% and today if you listen to a lot of discussions on CNN and other US TV channels, you will find the reason why this is happening is because like us they have gone and stratified their vaccination population on all these prioritization basis and it is proving to be a very tedious bureaucratic slow process and in fact they themselves are thinking of now being flexible and opening it up. Similarly, I think we also need to look at having a much more flexible model whether it is you know a 80-20, whether it is a 60-40, whether it is a 50-50, whatever percentage that the government comes up with, you should allow a small percentage to be deployed to the general population then only will the speed of vaccination accelerate. Open it up to the private sector because like in the RT-PCR testing case as long as the government was handling it we were woefully short of testing. It was slow and because of lack of capacity it was also slowing down even further. The moment the private sector got into it there was huge capacity expansion, the number of tests got ramped up and market forces also drove down the prices. So, I think here also the vaccines which will be deployed in the private sector ought to be price controlled and any way you have a Co-WIN app which with the private sector must be mandated to use so that anyone vaccinated, their data can be uploaded onto a common ICMR database or a health ministry database.

Barkha: So, you’re saying that involve the private sector, A and B, keep a percentage for general population who does not tick the box on vulnerable population and in this part the focus should be on working population for example, who do you classify as the frontline, doctors, health workers of course but what about delivery boys? Let’s take Zomato and Swiggy delivery?

KMS: Yes, I mean they are as exposed and vulnerable to the virus as a lab technician in a dental clinic or a municipal worker sweeping the streets of the town. So, I think you cannot differentiate between these people who is more important, who is more essential or who is more vulnerable. These are discussions that are not fair is what I’m saying. So, I just feel that you need flexibility in this model and I think the government ought to look at this flexibility very rapidly, involve the private sector to expand capacity and speed of delivery and make sure that you have some regulations that don’t allow black marketing, don’t allow any other kind of misconduct.

Barkha: When we can hold general elections on such a vast scale why not vaccination with the help of the private sector. We forget that India already makes 60% of the world’s vaccines so when we are sitting here, doubting Thomases, I think we have to remember that India’s track record on vaccine manufacturing is quite good. There are people who are still concerned because of this confused communication that has taken place. Professor Gagandeep Kang said the confusion is what does the drug controller mean by clinical trial user approval? Either you are doing a clinical trial, or you are not. So why rush for the approval if it is still in clinical trial mode. This is for Bharat Biotech.

KMS: I think basically the articulation of how the Bharat Biotech vaccine was approved was not properly explained. According to me what they were basically saying is what I said before, what they mean is that they want you to be followed up, since they still don’t have efficacy data. They feel that you can generate more data by giving vaccine without a placebo control to a larger number of people. It’s like an open label study, that is what we call it in clinical jargon, but you know which people can have access to, so that’s what is meant by that.

Barkha: There are questions in which people are saying that vaccine nationalism has led to the push for a swadeshi vaccine which made the government act in haste. Do you believe anything is happening in haste, it’s cutting corners or do you believe that the world over some corners are being cut because you’re in war not at peace?

KMS: Let’s be honest there is vaccine nationalism everywhere in the world. Why are you only faulting us here? I mean there’s been vaccine nationalism in the US, there’s vaccine nationalism in the UK, there’s vaccine nationalism in China, Russia, you name it. So, what’s wrong? I mean we have vaccines and we want those vaccines to be deployed. Every country wants vaccines to be deployed in its population. So, there is nothing wrong with that kind of vaccine nationalism and I don’t think it’s fair to just target India for that. Secondly, I don’t think there are any concerns that I have in terms of the way they were approved because every part of the world has approved vaccines in a very abbreviated fashion. Now you can always sort of knit pick and say this was done better than this but by and large it hasn’t followed due protocol in the normal sense of the word. So, from that point of view it’s a judgment call people are making on science not on the clinical format.

Barkha: I get that! Now I have to close with one last question, you have in fact been COVID positive and you have recovered, and I think you’re an example of what the new normal is that we may have to mask up and live and by the way we are going to have to mask up even after the vaccines because we could still be carriers even if we don’t get the disease. So as a COVID positive patient, I mean someone who has recovered from COVID rather, would you take the vaccine?

KMS: Yes, I would because you know I don’t know for how long I am protected because even though I’ve had COVID and a lot of people have had COVID you have also heard of lot of cases of reinfection. So you don’t know how long you’re protected for. I could be protected for a long time but I don’t know and there’s nothing wrong in me taking a jab of a vaccine to boost my immunity because it doesn’t do me any harm. It will only do me good.

Thank You!

To watch the full video, click here: https://youtu.be/cFKrWfqhEBQ