Q. To what extent do companies and regulators need to be transparent about serious adverse events in a clinical trial?
The question of how much information should be made public, at what level and be shared with whom is a contentious one. [Within the clinical trials framework], there is the participant, then there is the study team that knows who the participants are and it is expected to protect their data.
The study team [led by the principal investigator] is overseen by the institutional ethics committee. When a new product is being tested, the company that has made the product becomes the sponsor for the trial. This company cannot ask for identifiable information of the participant. The company, usually, will send independent monitors [like a clinical research organisation] that take on responsibility of maintaining quality of the study, in terms of paperwork, permissions, examining participants’ consent forms, visits etc and the overall performance of the trial site. Even they can have direct contact only with the study team and not the participant.
Institutional ethics committees can also monitor at an individual participant level. Then there is the Data Safety Monitoring Board (DSMB) that is also set up to protect participants, and these usually have experts looking at the trial data regularly to recognise problem patterns, which is usually reflected through a cluster of cases. For example, if somebody is administered a vaccine and hits a bug, it is unlikely to be related [to the vaccination]. But if there have been accidents with other participants while they have been in the trial, this would be a signal picked up by DSMB and investigated. That’s the kind of oversight available [in the system].
When you do a trial, you are always erring on the side of caution. Anything that sends a participant to the hospital or results in death is going to be treated as a serious adverse event [SAE] and investigated. And then a determination has to be made whether that SAE is related or not.
Now, coming to the issue of what all should be in the public domain and how much information should be shared. Sometimes, people ask for too much information without recognising the uselessness of it. There is always an opportunity cost. You can ask me to make every record identifiable and post it on a public website. That is obviously doable, but how much is it going to cost and how much is it going to delay my group, and its ability to test new interventions? And what value will it add? In the interest of transparency, we can be 100 percent transparent, but that will have very low utility value. Q. A participant taking legal action after having an adverse event during the clinical trial process is unprecedented. While the company [Serum Institute] and the principal investigator say the SAE is not related to the vaccine, the regulator [Drugs Controller General of India] has not commented. Is that a cause for mistrust among the public regarding the vaccination process?
The health secretary has come out and said that it is unrelated, so has the investigator and the sponsor. I looked at the discharge summary of the patient participant and in the initial admission diagnosis, they had included vaccine-included encephalopathy as a differential. By the time the patient was discharged in October, they had already got an alternative diagnosis through follow-ups with a rheumatologist, indicating this person has an auto-immune disease. Why should the regulator go beyond what has already been determined?
The fact that this person went to court because he does not believe his doctor’s diagnosis or the institution’s diagnosis is something that he has decided to do. I am sure he is absolutely convinced that this is vaccine-related, but this is the first time he is participating in a clinical trial. He is not a medical professional and does not understand that SAEs happen all the time.
Here is a person who has, according to his investigation, a low vitamin B-level, a low B12 level as well as all the other things we’re hearing about now. The fact that you identify low vitamin B-levels ten days after vaccination does not mean the vaccine drove down the vitamin B-level. Similarly, if you fall ill and are very sick, it doesn’t necessarily mean the vaccine caused that illness. Auto-immune diseases also occur after vaccination.
The Hepatitis-B vaccine, for example, is a very safe vaccine, but it does lead to certain auto-immune phenomena, very rarely, one in a million. But you can only make that association appropriately only after you’ve given the vaccine to millions of people. In India, the AstraZeneca vaccine is being given to 1,600 people. What is your chance of being able to associate a rare SEA to the vaccination, even one that happens in 10,000 people? You won’t be able to pick up if you’re doing the trial only with 1,600 people.
That said, anybody who gets sick, whether related to the trial or not, deserves to be handled appropriately and treated as early as possible.
If you are participating in a trial, you have volunteered yourself for the good of the society. So your concerns need to be taken very seriously and it is the investigator’s and the company’s responsibility to make sure they do their best to address your concern. I find it very difficult to believe that the principal investigator and the institution [Serum], which is very highly-regarded, were completely callous about this person. So the fact that this participant says they completely ignored him, nobody contacted him… it seems difficult to accept that clinical trialists would behave like this. Q. Do you think there is a general mistrust among people regarding the vaccination process given the general opaqueness of state and non-state authorities?
Where clinical research is concerned, we have created an atmosphere where nobody trusts the researcher. But if we want the benefits of new research, why do we think we should be exempted from participating in it? One of the principles of ethics is justice. Everyone should have the right to participate in clinical trials that will lead to better interventions for tomorrow. But if you have one group that says, “I will not be a guinea pig but I want whatever comes out of that research”, is that appropriate? That seems to be the line used by many people to say that Indians are vulnerable and must be protected, but they must also have access to the best new treatment. I see an issue there.
If you look at the West, one of the measures they have of the academic performance of an institution is what proportion of their patients are on clinical trials. The higher the better. That means, your doctors and research staff are academics seeking to improve treatments for tomorrow. In India, you don’t have any large hospital where even five percent of patients are on clinical trials, whereas in other places, this number is 50 percent and above.
We need to change the picture of clinical research in this country, and understand that without human experimentation, there are no new treatments and prevention strategies. And in order to do that, we have to build better trust in the system. Q. How exactly could one incentivise clinicians who undertake clinical trials and at the same time build trust among people?
I think incentivising people is by clearing their path to do research. Many of our best clinicians are overwhelmed by clinical work, but somehow they find time to do academic research. To create an environment where clinical trials are done well requires a re-shaping of the academic research system. It is not impossible, the mechanism exists everywhere. And for many doctors, the reward and incentive are participating in designing and doing the studies that shape tomorrow’s practice. We need more conversations around the need for clinical research and how to improve India’s standing. We have such a huge patient population and thinking about how we benefit them should be the basis of the research we undertake. Building trust is about communication, being open, transparent and sharing information. Q. On the heels of Pfizer getting clearance for emergency use authorization (EUA) in the UK, Serum Institute is making a request to the regulator to allow EUA in India. In the larger public narrative, do you think there is a misunderstanding that EUA is equivalent to licensure, and is that a concern?
Yes, it is a concern. The amount of data that Pfizer had collected for EUA is more than the data they had originally thought they would need to be able to go for a full licensure. The fact that they have gone for an EUA is about how much other information is required for a full licensure. It will need laboratory investigations, a deeper dive into the data, and making sure they submit the full scope of information in their application. I have no doubt that based on the studies they have done, they have enough data already for a full licence. It takes months to write an application for full licensure. The documentation requirement for an EUA is less. So Pfizer has an EUA in the UK, they will get it in the US by next month. These are all good things and they are doing this on the basis of having enough information actually for a full licensure.
Now when we think about the Serum Institute going to the regulator in India… given that they have recruited 1,600 people in India, they should provide to the regulator at least two months of safety and immunogenicity data. And they should provide to the regulator the information they have from the AstraZeneca trial globally. Because that’s where the efficacy data is coming from. If the safety and immunogenicity in India and the UK are equivalent, then I see no reason why we can’t take the efficacy data from the UK, accept that and give the vaccine an EUA in India. Q. There are talks about the vaccine candidate being available for sale in the private market by early 2021. Are there any challenges you anticipate here?
My worry is about equity. In India, we already have vaccination systems by the private sector and the public sector. In the private sector, you have access to many more vaccines than you do in the public sector. This is the first time when we’ve had a brand new disease that affects everyone equally. Should you create a situation where if you are rich, you can protect yourself, but if you are poor you cannot? To me, every rich person would be taking away a dose of vaccine that will be given to a poor person. So that’s why I think whatever vaccines they decide on, the priority groups need to come first.
If the government decides that they are only going to buy around 300 or 600 million doses of the vaccine, who is it going to give it to? And based on what principle does it decide that the vaccine is going to these people in this order? So what we need is clarity around that approach.