vaccine efficacy

Watch | ‘Covovax Better Than Covishield as Booster Dose’: Gagandeep Kang

The virologist said there is currently no data available on the immune response generated by Covaxin.

In light of the Union government’s decision to authorise booster doses (or as it insists on calling them, precautionary doses) of COVID-19 vaccines for healthcare workers, frontline workers and people over the age of 60, certain key questions emerge about the efficacy of various vaccine combinations and how the administration of these boosters should be carried out. The Wire‘s Karan Thapar put some of these questions to Gagandeep Kang, professor of virology at the Christian Medical College in Vellore and a member of the government’s COVID working group.

Regarding which vaccine should be used as a third dose, Kang said that there is presently no data in India. She did, however, cite the COV-BOOST study from the University of Southampton, recently published in The Lancet, which gauged the immune response generated in individuals who had already received two doses of the AstraZeneca (Covishield) vaccine by either a booster dose of the same vaccine or one of the Novavax (known in India as Covovax) vaccine.

The study found that a third dose of Covishield increased the Geometric Mean Ratio (GMR) by 3.25 while a booster dose of Covovax increased the same by eight times and one of an mRNA vaccine did so by 24 times. There is currently no data available on the immune response generated by Covaxin or Corbevax, the two other vaccines available in India.

Kang, here, stressed that the results of this study do not represent efficacy but rather, immunogenicity (the ability to generate an antibody response) and that this immune response is only one arm of the immune system.

In the interview, Kang breaks down the results of the study further, speaks about who should receive this booster dose first, the optimal time to receive it and more such questions.

Kang said she has no problem with the third jab being given nine months after the second, even though in Europe and America boosters are given six months after the second jab and in many countries even three months after the second jab. In fact, Kang said, “It is very possible a longer gap may be better but we have no data as yet.”

Watch | ‘Nationally The Worst Is Over and in Kerala, We Are at The End of a Tunnel’

Professor of Biostatistics, Epidemiology and Global Public Health, Bhramar Mukherjee, says that her mathematical models do not foresee a big third wave.

One of America’s most highly regarded professors of Biostatistics, Epidemiology and Global Public Health, whose mathematical models have been closely and accurately tracking the COVID-19 trajectory in India since the start of the pandemic, has said “nationally the worst is over” as far as the second wave is concerned and, with specific reference to Kerala, she adds “we’re at the end of a long tunnel and we can see the light”.

In a 23-minute interview to Karan Thapar for The Wire, Professor Bhramar Mukherjee of the University of Michigan, also said that her mathematical models do not foresee a big third wave. She said there will be small local and regional outbreaks, what she calls bumps, but they will not involve numbers anything like the massive number of cases India saw in April and May.

Mukherjee said that at the moment the national R number is 0.85 and for Kerala the R number is 0.8.

Speaking about the future nationwide trajectory of COVID-19, Mukherjee said: “If we map case counts today to the recent past then you will see that in January this year we had 18-20,000 cases a day. It fell to 10,000 a day by February and thereafter started to rise. Do we expect that to happen again? No. The worst is over.”

Asked how concerned she was by the fact that 34 districts, across 9 states and Union Territories, have a positivity rate of at least 10% and a further 28 districts, across 12 states and Union Territories, have a positivity rate between 5 and 10%, Mukherjee said she was not particularly concerned because the overall nationwide positivity is 1.5% and going down.

Speaking about reports from the Institute of Mathematical Sciences in Chennai that the R number in four major cities – Mumbai, Kolkata, Bengaluru and Delhi – keeps popping above 1.0 and then dips below only to go up again, Mukherjee said this was more a reflection of the fact that when you deal with a small number of cases – as in Delhi – and the daily tally increases from 30 to 40 it can have a disproportionate impact on the R number.

Speaking in greater detail about predictions made in June and July that India would experience a third wave, which so far hasn’t happened and looks unlikely, Mukherjee said: “Our models never engaged in imminent third wave prediction.” She seemed to suggest “the certainty about a third wave which was being expressed in June and July” is baffling.

Asked if she would be worried if, despite the fact, 73% of the adult population has received a single jab and nearly 30% both, India, in the present circumstances, fails to meet its target of fully vaccinating the adult population, Mukherjee said she would be worried because “we have vulnerable pockets of population”.

Speaking about the festive season, she said since large gatherings are going to be unavoidable, her advice is people must wear masks, particularly when they are in large gatherings and particularly when you don’t know the vaccination status of others.

Finally, Mukherjee said she does not share the confidence expressed in earlier interviews by Professor Soumya Swaminathan of the WHO and Professor Gagandeep Kang of the Christian Medical College, Vellore, that by the end of 2022 COVID-19 could convert from its present pandemic status to an endemic status and at that point, it will be no greater a threat then influenza.

Mukherjee said there are too many unknown variables to say this with any certainty. She also said she could not accept any comparison between COVID-19 and influenza because COVID-19 often leads to long COVID, which is not the case with influenza.

Watch the full interview here.

Watch | If Worrying Variants Don’t Emerge, India is Near Endemic Stage: Gagandeep Kang

Prof. Kang said the time has come for India to rethink its attitude to COVID-19 in relation to many other health concerns that haven’t got sufficient attention over the last 18 months.

In an interview that will be reassuring for many, one of India’s foremost professors of Virology and, more importantly, a member of the government-appointed Covid Working Group, has said that “in the absence of the possibility of new worrying variants”, India is at or approaching the endemic stage of SARS-CoV-2.

Agreeing with what Prof. Soumya Swaminathan, the Chief Scientist of the WHO, said to The Wire on August 23, Prof. Gagandeep Kang said that India is likely to see ups and downs in specific locations but not a nationwide wave in any way similar to the frightening second wave of COVID-19. Prof. Kang also said that this is not the right time for boosters except, possibly, for immuno-compromised people. Also, in a particularly significant moment of the interview, Prof. Kang said the time has come for India to rethink its attitude to Covid and the predominant importance so far given to it. Now it must be thought of in relation to and with relevance to many other health concerns that haven’t got sufficient attention over the last 18 months.

The ones she mentioned were cancer, diabetes, tuberculosis and problems connected with maternal pregnancy. As she put it: “The time has come not to treat SARS-CoV-2 the way we did at the start of the pandemic… but think of it in relevance to other illnesses.”

In a 35-minute interview to Karan Thapar for The Wire, Prof. Kang said “we cannot predict a third wave in the absence of a radical change in viral behaviour or a radical change in human behaviour”. She said she cannot understand the basis of the fear and apprehension of a looming third wave as well as the comments made by ‘experts’ on television and in newspapers. She said whilst new variants could emerge “because of mutations or because of some form of recombination”, as yet we don’t know of them and, therefore, she cannot understand the basis on which people are predicting or fearing a third wave.

Elaborating on her view that India is at or near an endemic stage, Prof. Kang said the time had come for India to rethink its attitude to SARS-CoV-2. She cited the example of typhoid to illustrate how we should, perhaps, start thinking about SARS-CoV-2. She said typhoid is endemic, we know how it’s caused, we know how to handle it and we also know we can do better. It’s not a prime concern. SARS-CoV-2 is heading in that direction. And, therefore, we should now balance our time and attention to COVID-19 with our attention to other illnesses, which haven’t got the importance they deserve in recent months, such as cancer, diabetes, tuberculosis and maternal problems connected with pregnancy.

Prof. Kang also said that the time had come for us to rethink our attitude to testing. The original emphasis on test and trace, which was at the core of our handling of COVID-19 at the start of the pandemic, now needs to be rethought and altered given the present situation where we could be at or near an endemic stage.

Speaking to The Wire about the overall COVID-19 picture in India at the moment, where the seven-day average of daily cases has fallen from 42,881 on September 2 to 37,237 on the 9th and 31,074 on September 16, Prof. Kang said that whilst the “trajectory is good” it’s also true that “wherever you look at the Delta variant, after a sharp spike is over, the number of cases haven’t returned to the lowest pre-Delta point”. That is also true of India. It’s possible that cases can plateau at a level of around 30-35,000 a day for a fairly long period. Something similar is happening in Britain at the moment.

Speaking specifically about Kerala, where the seven-day average of daily cases was 29,804 on September 2, 26,794 on September 9 and 19,505 on September 16, but daily cases have once again increased to 20-22,000 levels, Prof. Kang said “we can’t expect the trajectory to be maintained day after day”. She suggested that as long as the weekly average of daily cases is going down that is a sign that numbers are diminishing.

Prof. Kang also said that another positive note in Kerala is that the state’s vulnerability, because its sero-positivity levels were so low, is now increasingly being countered by the very high levels of vaccination and, therefore, the size of the vulnerable population is diminishing.

When asked by The Wire if, despite India’s record-breaking performance of 25 million jabs in one day on the 17th, the country fails to fully vaccinate every single adult by the end of the year how much of a concern that would be, Prof. Kang said “it would not be the end of the world”. She suggested the high levels of sero-positivity (68%) have given a fair measure of protection. She also said targets are often set and missed. This would be one more.

Asked by The Wire about booster doses, which are now being either considered or given by countries like the US, UK, Israel and much of Europe, Prof. Kang said “the time is not right for boosters for anyone except, possibly, immuno-compromised people”.

Prof. Kang pointed out that whilst vaccine efficacy against infection does diminish over a period of six months the efficacy against serious disease remains high. Therefore, she asked, whilst boosters may have to be given what is the right time to do so? She said the research available internationally does not present a clear and decisive answer. We need more information. A second concern is if boosters are given which vaccine should be used? Should it be the same one or a different one?

In the interview to The Wire, Prof. Kang was asked if there is a percentage level of adult vaccination at which India can feel relatively secure in opening up, as the UK has done, and she said it is very hard to answer this question because the percentage of the population in India comprising children, who are unvaccinated, is much larger than in the UK. So, as she put it, even with every adult vaccinated India’s situation will not be analogous to that of the UK.

Finally, Prof. Kang agreed with Anurag Behar, the CEO of Azim Premji Foundation, about problems affecting vaccination in rural India. Please see the interview for details of this. However, Prof. Kang explicitly said the government must make a deliberate and conscious effort to reach people in rural areas, who are distant and also uninformed, to ensure that they get vaccinated. Otherwise they could be left out and that could be a serious problem.

The above is a paraphrased precis of Prof. Gagandeep Kang’s interview to Karan Thapar for The Wire. Watch the full interview here:

Only 56% Of Healthcare, 47% Of Frontline Workers Fully Vaccinated: Health Min

Union health secretary Rajesh Bhushan called the shortfall a “serious concern” and said state governments should fully vaccinate this group of workers asap.

Bengaluru: When Prime Minister Narendra Modi flagged off India’s COVID-19 vaccination drive on January 16, 2021, he said the first phase would cover the country’s frontline and healthcare workers by July.

But on June 10, the Union health ministry admitted that while 82% of healthcare workers had received at least one dose, only 56% had received both doses. Similarly, 85% of frontline workers had received at least one dose and 47% had received both doses.

New Indian Express quoted Union health secretary Rajesh Bhushan saying the shortfall was a “serious concern”, and that state governments should fully vaccinate this group of workers asap.

The authors of a study of nearly 9,000 healthcare workers at Christian Medical College, Vellore, said some of them couldn’t get the second doses “initially due to vaccine shortage and subsequently, despite vaccine availability, due to changes in guidelines on the interval between doses.”

After India’s vaccination drive began in earnest, the country began reporting supply issues by March. At the same time, the government expanded eligibility for vaccination to the 45+ age group in April and to the 18-44 years group from May 1.

Both the Indian government and the vaccine-makers had overestimated the manufacturing capacity. The government also undertook ‘vaccine diplomacy’, exporting 58 million doses to 70 countries by mid-March and 66 million doses to 94 countries by late April.

While local manufacturers couldn’t keep pace with the rate of vaccination, the supply of the one other vaccine in India’s drive – Sputnik V from Russia – faltered as well.

The first two or three months of the vaccination drive were also marked by vaccine hesitancy, directed especially at Covaxin, which India’s drug regulator had approved without data from its phase 3 clinical trials.

Also read: US FDA Denies Bharat Biotech’s Covaxin Emergency Use Approval

There were also issues with the vaccine registration system and a shifting vaccination policy. On the former: the CoWIN portal has been criticised because it makes the registration process much harder for people who are not technologically savvy.

On the latter: between late April and early June, the Modi government adopted a procurement policy in which the Centre would buy Covaxin and Covishield doses at lower rates from vaccine-makers, while state governments and private hospitals could negotiate separately for their requirements.

The underlying moral and ethical issues drew the Supreme Court’s ire, as well as that of numerous politicians and independent experts. The government subsequently restored its original policy of centralised negotiation and procurement.

But taken together, these issues have ensured not even a fifth of the country has received at least one dose of a COVID-19 vaccine. At present, 14% of Indians have received at least one dose and only 3.3% have received both doses.

Healthcare workers are at greater risk of contracting COVID-19 because of their exposure to patients with the disease. The Indian Medical Association said on June 1 that 1,300 healthcare workers have died of COVID-19 since the pandemic began, almost 600 during India’s second wave.

Centre to Study Feasibility of Single Dose Covishield Regimen

The proposed study comes even as a study by English health officials said only two doses of Covishield provide strong protection against the B.1.617.2 variant of the coronavirus.

New Delhi: As preparation for a new COVID-19 vaccination strategy that hopes to scale up India’s daily administered doses to 1 crore by mid-July, the Centre plans not only to conduct studies on mixing different vaccines but also test the feasibility of giving just a single dose of Covishield, instead of the current two-dose regimen.

Previous reports had already suggested that the Centre plans to study a mix-and-match regimen, after trials conducted in Spain and other countries showed encouraging results. Now, NDTV reports that the study will “likely be completed in two to two and a half months”.

According to the report, the Centre will also assess vaccine data recorded on a new app which will make it easier to report adverse events after immunisation (AEFIs). The platform will be linked to the Co-WIN portal and allow people to report any concerns after they receive a shot. A district officer will follow up on these cases.

The other, more surprising, development is that the Centre is considering the possibility of prescribing only one dose of Covishield, the Oxford-AstraZeneca product produced by Serum Institute of India. The government has already stretched the gap between the two doses to 12-16 weeks, in a move that was seen as a way to tide over the shortage in vaccine supply.

NDTV reports that the government will first review the “impact of its decision to extend the gap” between the Covishield doses, which will “also help decide on a possible single-dose plan”.

“Single dose vaccination will help the government cover a much wider base of the population,” the report says, quoting unnamed sources, suggesting this move is also motivated by a desire to overcome potential supply-side issues. Over the past few weeks, there have been several reports of people who have received one dose of a vaccine unable to get a second dose.

Watch | India to Ignore UK Efficacy Data on 1-Dose Covishield for B.1.617.2, Stick to 12-16 Week Gap

Another assertion made by these same sources gives cause to doubt the wisdom behind the proposed plan. They said that the AstraZeneca vaccine candidate “started out as a single dose option before effectiveness studies recommended two shots”. However, these sources added that there is a view that a “single shot is enough protection from the virus”.

“Vaccines like Johnson & Johnson and Sputnik Light, which are based on a similar principle as AstraZeneca, are single dose, sources point out, so Covishield should work as one too,” the NDTV report says.

However, the scientific foundations of these assumptions is not known. A recent study by Public Health England (PHE) on the B.1.617.2 variant of the novel coronavirus, first identified in India, found that only a double dose of Covishield could provide strong protection against COVID-19. The study said:

“Two doses of the AstraZeneca vaccine were 60% effective against symptomatic disease from the B.1.617.2 variant compared to 66% effectiveness against the B.1.1.7 variant [first identified in the UK]… Both vaccines [AstraZeneca and Pfizer] were 33% effective against symptomatic disease from B.1.617.2, 3 weeks after the first dose compared to around 50% effectiveness against the B.1.1.7 variant.”

In light of this study, experts had raised concerns about the government’s decision to expand the gap between two Covishield doses to 16 weeks, saying it might not help in reducing symptomatic infections. If the Centre decides to adopt a single dose regimen, it is likely that these concerns will be further heightened.

However, Narendra Kumar Arora, chairperson of one of India’s COVID-19 working groups, recently told Karan Thapar in an interview to The Wire that the Centre will ignore the results of the UK study, highlight issues such as small sample size and the uncertainty band surround the 33% efficacy estimate.

India has so far administered just over 21 crore vaccine doses, of which 88.94% are Covishield. While Bharat Biotech’s Covaxin represents a majority of the remaining doses, a small fraction of Russian made Sputnik V has also been administered.

As of Monday morning, the country had recorded over 2.80 crore confirmed cases of COVID-19 and has reported 3.29 lakh deaths.

Watch | ‘Delay Second Covishield Dose for 8-12 Weeks, Permit Open Market Sales for Unused Vaccines’

In an interview with Karan Thapar for The Wire, professor Gagandeep Kang answered several questions about the Oxford-AstraZeneca vaccine, which is known as Covishield in India.

Gagandeep Kang, who is widely considered India’s top vaccine scientist, has said the Indian government should delay the second dose of the Covishield vaccine so there is a 8-12 weeks interval between the first and the second. This is what a World Health Organization (WHO) guidance, dated February 10, has advised.

Kang, who is the Wellcome Trust Research Laboratory professor at the Christian Medical College at Vellore and a member of the Britain’s prestigious Royal Society, revealed that she is a member of the strategic advisory group of experts who have helped the WHO come to this conclusion.

In a 41-minute interview to Karan Thapar for The Wire, professor Kang answered several questions about the Oxford-AstraZeneca vaccine – known in India as Covishield – which have been the subject of concern and discussion internationally but have not attracted attention in India and have not been flagged or spoken about by the government.

Elaborating on her advice that the second dose of Covishield should be given after an interval of 8-12 weeks, Kang said: “I agree a longer interval will be better”. She added: “If I was in a position to make decisions, I would recommend the second dose is given after an interval of 8-12 weeks.” Asked if the government telephoned for her advice, Kang replied “absolutely”.

In the interview to The Wire, Kang also spoke about the decision by Germany and Denmark not to give the Oxford-AstraZeneca vaccine to people over 65 because they have doubts about its efficacy for this age group. Kang said she believes these doubts are “unlikely to be justified”. However, she accepted that the number of people in the Oxford-AstraZeneca trial group over the age of 65 was small (it was one-tenth of the sample) and this is too small a number for firm conclusions. The WHO, in its February 10 guidance, has recommended the vaccine for use for persons aged 65 years and older.

Kang also spoke about South Africa’s decision to temporarily discontinue the Oxford-AstraZeneca vaccine because they believe it’s ineffective against mild and moderate forms of the South African strain. She believes this was clearly shown by South Africa’s research although the research group was small. She also said statements made by Oxford University Dons that AstraZeneca will be effective against serious illness caused by the South African strain are based upon the belief that all vaccines tend to be most efficacious against serious disease. This, she pointed out, is an assumption in the case of AstraZeneca and not based on hard evidence. The truth is, as she put it, “we just don’t know”.

Speaking about the general confusion about the efficacy of AstraZeneca, which is why the Swiss have decided not to give it at all, Kang accepted “the data is confusing”. She said “a fair amount of confusion surrounds the results of AstraZeneca”. She said this is partly because mistakes were made in initially estimating the potency of vaccine doses. She pointed out that AstraZeneca has not made vaccines before whilst the University of Oxford has a lot of experience in this field.

AstraZeneca initially said two full doses would give 62% protection but half a dose followed by a full dose would give 90% protection. Thereafter, the British said a month after the first dose there was 70% protection which would go up to 80% after two further months. On this basis, the British were the first to formally delay the second dose for up to 10 or 12 weeks.

Kang also discussed the French decision to only give one dose of any vaccine to people who have had COVID. She raised the concern that if the decision is based upon RT-PCR results, then it runs the risk of giving only one dose to people who may have got false positive results and were not really infected and, therefore, do not have the protection that comes with infection.

Finally, Kang said that given the vaccine hesitancy prevailing, the government should permit open market sales of vaccines that are not used by the public health system i.e. Pfizer, Moderna, Sputnik and the Chinese vaccines. They could be made available immediately. This would be in addition to and separate from the public vaccination programme based upon the government’s prioritisation strategy.

Kang was also asked whether there was a need for the prime minister and the president to set an example by publicly taking Covaxin or Covishield to encourage others, and she replied saying that she did not believe that we need public figures and celebrities to act as role models. She said in health matters it’s incumbent on every individual to take the right and sensible decision himself or herself.

However, in this context, she did once again repeat something she has said in earlier interviews to The Wire that we do not have evidence of the efficacy of Covaxin.

The above is a paraphrased precis of Gagandeep Kang’s interview to Karan Thapar for The Wire. Although recounted from memory, it’s not inaccurate. There is, of course, a lot more in the interview than has been covered in this precis. Please see the full interview for a better appreciation and understanding of professor Kang’s arguments.

Watch the full interview here.

How Effective Are The Covid-19 Vaccines?

While the Pfizer and BioNTech vaccine offers the highest efficiency at 95%, the Sinovac vaccine offers 50%.

Last week, there was more good news on the COVID-19 vaccine front with US firms Johnson & Johnson and Novavax releasing efficacy data from late-stage trials. Johnson & Johnson’s JNJ-78436735 candidate is being developed by its subsidiary Janssen Pharmaceuticals in Belgium and the single-dose jab was shown to be 66% effective in global trials. Interestingly, that figure was actually higher in its US trials, where it reached 72%. The US has ordered 100 million of doses of the vaccine and Johnson & Johnson has stated that it intends producing up to one billion doses in 2021. NVX-CoV2373 from Novavax has also shown to be 89% effective in UK trials and it works against the new variant of COVID-19 detected there. Both of the vaccines will now need to be reviewed by regulators before they can be pressed into use.

The University of Oxford and pharmaceutical giant AstraZeneca vaccine passed that milestone in the EU on Friday amid a bitter dispute over vaccine shortages and unfulfilled contract obligations. When AstraZeneca released initial data from trials in late November, it showed that ChAdOx1 nCoV-2019 was 70.4% effective, though it can achieve up to 90% protection if a half dose is taken initially, followed by a full dose. The positive results came after Pfizer and BioNTech reported that their vaccine is 95% effective at preventing COVID-19 while Moderna announced that their jab also has 95% efficacy. Both vaccines are based on introducing genetic material, mRNA, into the human body in order to produce spike proteins which prevent the coronavirus from entering human cells.

The Oxford University/AstraZeneca vaccine is adenoviral and is based genetically modifying a common cold virus that used to infect chimpanzees. Despite the positive results, there is no data regarding whether the candidates prevent the coronavirus from being transmitted as well as for how long protection lasts. Even though it has a lower efficacy from a single dose, the Oxford/AstraZeneca vaccine has been shown to work effectively in different age groups, though Germany has prohibited it for over 65s, citing a lack of data.

It is also significantly cheaper than other COVID-19 vaccines and much easier to store, meaning it can be distributed more easily, potentially making it the shot of choice in poorer parts of the world. Its ease of storage characteristics are shared with Johnson & Johnson’s shot which can last months in a regular refrigerator while its single dose provides it with a further advantage over the competition. The Moderna vaccine can be stored at temperatures of between 2C and 8C for 30 days while the Pfizer/BioNTech vaccine, on the other hand, must be stored at -80C, exacerbating logistical challenges. It usually takes a decade to develop such a vaccine but, astonishingly, the process for creating these jabs has taken a mere 10 months.

It is also important to mention the efforts of other countries, particularly Russia and its Gam-COVID-Vac jab, better known as Sputnik V, which is being developed by the Gamaleya Research Institute of Epidemiology and Microbiology. The Russian Health Ministry announced that Sputnik V is 92% effective, though that figure was controversial as it was approved for distribution despite being tested in a small group of people. According to late-stage trial data published in The Lancet involving some 20,000 people, Sputnik V is completely safe and is one of the world’s most capable COVID-19 vaccines with an efficacy of 91.6%, closely matching those controversial initial estimates. Elsewhere, China’s Sinovac Biotech vaccine Coronavac has shown efficacy of 50% in Brazilian trials.

This article was first published on Statista.

Why DCGI’s Covaxin Verdict Forces First Vaccine Recipients To Make a Tough Call

We have a situation in which at least some people might see no other option but to get Covaxin, irrespective of their doubts about its safety and efficacy.

Bengaluru: In a statement at 11 am on January 3, the Drug Controller General of India (DCGI), Dr V.G. Somani, said the Covaxin COVID-19 vaccine candidate was being approved in “clinical trial mode”. Multiple observers – including noted clinician and vaccine expert Gagandeep Kang – were befuddled about what he could have meant.

At 9:40 pm on the same day, Union health minister Harsh Vardhan said on Twitter that those given Covaxin will effectively be participants in a clinical trial to help determine the vaccine’s safety and efficacy.

While Dr Somani’s statement on January 3 mentioned “clinical trial mode”, another note published by the subject expert committee of the Central Drug Standards Control Organisation (CDSCO) said Covaxin would receive “grant of permission for restricted use in emergency situation in public interest as an abundant precaution, in clinical trial mode, to have more options for vaccinations, especially in case of infection by mutant strains”.

A grant of this description is not recognised in India – specifically, by the New Drugs and Clinical Trials Rules 2019 and the Drugs and Cosmetics Act 1940. Dr Somani also refused to take questions from reporters, so there is considerable confusion. However, Vardhan’s tweets confirm that the CDSCO, the DCGI and the Union health ministry are accelerating Covaxin’s public exposure using the new, more contagious strain of the novel coronavirus as an excuse.

Also Read: COVID-19 Vaccines: What We Lose When We Lose Public Accountability

A new trial

“Up front, I do believe that eventually Covaxin would turn out to be safe and more than 70% efficacious,” Shahid Jameel, a noted virologist and currently director of the Trivedi School of Biosciences, Ashoka University, Sonepat, told The Wire Science. “I say this based on the platform, which is widely used, and on Bharat Biotech’s own track-record of successfully making inactivated viral vaccines. My concerns are with the process and the utterances of people in responsible positions.”

In India, clinical trials are regulated by a clutch of legal, scientific, ethical and democratic principles administered by three entities: the CDSCO, the company or institution sponsoring the trial and the specific site at which the trial is conducted. Apart from this, the journals that publish papers arising from trials have their own requirements. These boundaries in turn give rise to specific circumstances and contexts in which clinical trials can happen; if trials cross these boundaries, they become at risk of breaking some or all of the rules that guide their conduct.

To understand what these boundaries look like, consider examples in which trials crossed them. As Dr Jammi Nagaraj Rao has written about Biocon’s botched itolizumab trial: the researchers who conducted the trial changed the trial outcomes after it kicked off, didn’t specify how they calculated the sample size, weren’t clear on differences in effect sizes between groups of participants, used an unclear dosing strategy and hid the outcomes of some patients. A different trial indicated that favipiravir is not an effective antiviral agent against COVID-19 – but the researchers published a press release saying the opposite.

In a third instance, Bhopal-based activist Rachna Dhingra alleged on January 3 that a hospital was administering the Covaxin vaccine candidate among unsuspecting people who hadn’t been told they were really part of a clinical trial. Fourth example: Bharat Biotech reportedly asked the principal investigators at its trial sites to invite people older than 50 to participate saying that, otherwise, they might have to wait longer to get a chance to receive Covaxin. And fifth: At the time the Indian Council of Medical Research (ICMR) approved Bharat Biotech’s phase 3 clinical trials for Covaxin, one analysis found several lapses in the choice and constitution of ethics committees that would oversee fair conduct of the trial.

Even now, ICMR and AIIMS New Delhi director Randeep Guleria rushing to the DCGI’s defence has raised red flags. (Guleria told NDTV that Covaxin would only be used as a “back up”.) As Jameel pointed out, “ICMR is a partner in the development of Covaxin and AIIMS is one of the trial sites. This is deeply troubling.”

Bharat Biotech’s Covaxin. Photo: File Image

Where is phase 3?

An ‘open’ clinical trial to be conducted with a vaccine candidate on the basis of “rolling reviews” is at risk of repeating these transgressions – and others besides.

For example, Bharat Biotech, the company behind Covaxin, has already reported that it has recruited around more than 20,000 volunteers for Covaxin’s phase 3 clinical trials. According to a health ministry press release published on January 3, Bharat Biotech has already administered Covaxin to ~22,500 participants, and has determined the vaccine to be safe based on their response.

However, the company has not shared the efficacy and safety part of this information with the public – not even with independent scientists via manuscripts in scientific journals – while experts have said it ought to. The company has only shared it with the CDSCO, pursuant to Covaxin’s approval.

Aside from the contents of the proceedings, Jameel disputed the proceedings themselves. “If approval requires both safety and efficacy data for a representative population, phase 2 safety and immunogenicity do not fulfil those criteria. That is why we do a phase 3. It is the closest you get to a population,” he said. “Where is that data? Vaccines are not drugs. They are given to healthy people. They are prevention, not treatment. Both safety and efficacy required.”

In addition to safety concerns, which haven’t escaped attention, there are two claims about the vaccine candidate in the public domain for which the basis is unknown. First, that the vaccine is expected to be around 60% efficacious. Second, that ICMR thinks Covaxin is likely to be more effective against the new strain of the novel coronavirus.

“The [subject expert committee] argument is that Covaxin would work as some sort of insurance against the UK variant, but I am completely unaware of any data on Covaxin’s efficacy on any strain of SARS-CoV-2, let alone any special efficacy against the variant strain,” Kang told Deccan Herald. “It is quite a stretch to say it would work against the UK variant.”

Even Krishna Ella, chairman and managing director of Bharat Biotech, said during a press conference on January 4 evening that his vaccine candidate’s “effectiveness against the virus’s mutant strain is a hypothesis” – that there is no data on this front yet and that the company will produce “confirmatory data” in “one week’s time”.

With Covaxin, a vaccine candidate of unspecified safety and efficacy in the fray, its roll-out must also include plans for dealing with adverse events. According to the 2019 Rules, a person injured in the course of a clinical trial is entitled to free medical attention for as long as required and financial compensation from the trial sponsor. While Bharat Biotech is the sponsor for the ‘closed’ trial involving ~22,500 volunteers, it’s not clear who the sponsor for the ‘open’ trial is. But considering the DCGI, the CDSCO and the health ministry have approved Covaxin’s use in “clinical trial mode”, they are likely to share responsibility as well.

Second, to obtain ‘good’ data from a clinical trial requires ‘good’ trial design. This means, among other things, that the number of people in the two groups – the control arm and the vaccine arm – has to be determined beforehand, based on what outcomes the researchers are looking for, what biases and confounding factors they need to evade, and how statistically significant the results need to be.

As things stand, the DCGI and Vardhan have both confirmed that the health ministry is approving Covaxin for emergency use because of the novel coronavirus’s new, more-contagious strain. But we don’t know if Bharat Biotech’s decision to have 26,000 participants in Covaxin’s phase 3 trials accounts for the approval.

Then there is the considerable time and monetary cost. “For any clinical trial, there are both inclusion and exclusion criteria,” Jameel explained. “Would those be followed for every person who is vaccinated?” He pointed to the exclusion criteria attached to Covaxin’s phase 3 clinical trials: if any volunteer met any of these conditions, they would be excluded from the trial. “For example, would every vaccinee be tested for prior infection using antibody and RT-PCR tests? Would every vaccinee be tested for HIV, HBV and HCV? Would this not add to cost and logistics?”

Source: CTRI record

Alternatively, the company and the health ministry could together decide to treat Covaxin’s ‘open’ trial as a new study. If Covaxin’s approval hinges on the new strain, the ‘open’ trial could be used to determine if the candidate is indeed efficacious against the strain. Ella did say during his press conference that the plan for the ‘open label’ trial is to not have a placebo arm, and instead to “keep vaccinating and monitoring”.

On the flip side, such a study will effectively be a single-arm clinical trial or an observational study. And these are both less useful to determine the safety, efficacy and immunogenicity of vaccines than randomised controlled trials.

Also Read: All You Need to Know About Bharat Biotech and Covaxin During the Pandemic

Right to choose, without choices

In the final analysis, the health ministry has eroded Indians’ individual right to consent to medical treatment – under Article 21 of the Constitution. The government has previously said vaccinations will be voluntary. Government officials have also said that receiving Covaxin will be a choice and that recipients will have to sign a consent form before they do so. At the same time, the novel coronavirus – new variant or otherwise – and the subpar healthcare infrastructure in many parts of the country together make a vaccine less than optional, especially among frontline and healthcare workers, and among the elderly and people with comorbidities.

Add the fact that Covaxin’s credentials are mired in secrecy, and we have a troubling situation in which at least some people might see no other option but to take the vaccine candidate, irrespective of how doubtful they are that they will be protected.

As Jameel said, “Sidestepping processes and poor/complex communication will fuel rising vaccine hesitancy in India. There is already evidence of that on account of fast-tracked development timescales.”