Representational image of a vaccine being administered | Rawpixel
Representational image of a vaccine being administered | Rawpixel

New Delhi: As Bharat Biotech looks to complete recruitment for the phase 3 trials of its Covid vaccine candidate Covaxin, its pitch to potential volunteers has raised concerns.

The controversy stems from a Bharat Biotech document, accessed by ThePrint, that is meant to inform Covaxin trial sites about ways to address concerns raised by volunteers — or how to answer their ‘Frequently asked questions (FAQ)’. 

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One of the FAQs listed is: “Why should I participate in the Phase 3 Efficacy Trial for Covaxin and get vaccinated, when the government announced that persons above the age of 50 years will be vaccinated shortly?”

In response, the document states, principal investigators should tell recruits that the vaccine will protect them against Covid-19. The Hyderabad-based firm also wants recruits aged over 50 to be told that it is “advisable” for them to participate in the trial since it may take months for the government to reach them even if they are identified as a priority group.

Some experts have taken objection to the fact that the vaccine promises to be effective even as trials remain underway. Highlighting the risk, they pointed out that some of the recruits will be part of the trial’s placebo arm, and won’t be any more protected than someone who has received nothing.

Even as a principal investigator attached with one of the sites defended the document, saying it should be “taken in the right spirit”, another balked at the prospect of promising someone protection in a double-blind study, where even researchers don’t know which of the participants might get a placebo.

ThePrint reached the media representatives of Bharat Biotech and the Indian Council of Medical Research (ICMR), a collaborator on Covaxin, Friday via email and text message for comments on the document, but hadn’t received a reply till the time of publishing. This report will be updated when a response is received.

Also Read: Oxford Covid vaccine might become the first to get Centre’s nod for emergency use

What the document states

In its Phase 2 trial, indigenous Covid vaccine candidate Covaxin has been found to be safe with no serious adverse events, according to a non-peer-reviewed study released last week. However, the vaccine needs to undergo extensive Phase 3 trials before it can be cleared for use on the public. 

The basic difference between Phase 2 and 3 trials — both involving human subjects — is that the latter requires a far wider pool of participants to get a clearer, more accurate picture of vaccine efficacy and safety. 

As reported by ThePrint Saturday, Bharat Biotech is thousands of volunteers short of its target for Phase 3 trials. 

The FAQ document in question was released earlier this month, which is also when the government discussed an expert panel’s recommendation that those aged over 50 be included among the priority groups who will receive a Covid vaccine once it is approved.

The document quotes the central government’s announcement, saying, “When immunisation commences, it can be simultaneous also depending on the availability of the vaccine. It is possible that in the first month, there is limited availability of the vaccine but it will increase in subsequent months.” 

“As per the recommendations of the health ministry’s expert panel, the Covid-19 vaccine will be ‘distributed first in three groups’,” it adds, before listing the three proposed groups — one crore healthcare workers to be given “top priority”, followed by “two crore frontline workers that include the police, armed forces and disaster management volunteers”.

“Lastly, people above the age of 50 years and those under the age of 50 years with co-morbidities. The estimated population of the last category is close to 27 crore,” it states.

Based on “the above scenario”, it says, “it may take many months for the subjects above the age of 50 years to be immunised for Covid-19 vaccine, as per the government’s recommendations”.  

“Hence, it will be advisable to participate in the Phase 3 Efficacy Trial for Covaxin and get vaccinated to protect yourself against Covid-19,” it states.

Also Read: ‘How do we get there?’ – Bharat Biotech readies for uphill task of Covid vaccine roll out

Unethical to lure participants like this’

According to Dr Amar Jesani, editor of the Indian Journal of Medical Ethics, “the main point on which the document misguides PIs (principal investigators) and participants is that… it’s a good vaccine”. 

“They are assuming that their vaccine is already good enough. How can sponsors assume it?” 

He added, “The company violates the cardinal principle of clinical equipoise by saying that it can be given now rather than later on.” 

Clinical equipoise — considered a key principle of medical research — requires researchers to be uncertain about the relative merits of different interventions offered in a trial. This is meant to ensure that no trial volunteer is knowingly administered a disadvantageous intervention.

Jesani, who is a consultant on bioethics and public health, added that “telling people this vaccine is going to provide protection will create therapeutic misconception for the participant in presuming that the experimental drug is good enough”. 

“If PIs put it in practice, the participants will get more complacent,” he added.  

Another expert, Dr Anant Bhan, a researcher in the fields of global health, health policy and bioethics, raised similar concerns. 

“The document clearly has troubled language. The whole purpose of a phase 3 study is to establish efficacy (and continued focus on safety). This document presupposes efficacy but on what basis?”

Jesani said the company must “withdraw the document” as the larger implication of their move is that it may impact the final results of the vaccine trial. 

“Half of the participants are in the placebo arm. By giving the confidence to participants that they are safe after taking the shots, the participants may become complacent. The people in the placebo group, in reality, have got zero level of protection, hence, increasing their chances of getting the infection,” he said. “As people in placebo would get more infection, the result of those getting the vaccine would obviously look better.” 

A trial participant, meanwhile, said those of who possibly got a placebo would get vaccinated on priority, “possibly much earlier” than those to be selected for vaccination under round one.

“When I enquired how we will know if we have received the placebo or the actual vaccine, it was explained that only after Bharat Biotech gets the market authorisation from CDSCO, the placebo recipients will be informed that they have received a placebo and will be given the real vaccine. The good thing is that those of who possibly got a placebo will still get vaccinated on priority and possibly much earlier than most of the 300 million people being targeted for priority vaccination under round one,” said Rajiv Nath, managing director of Hindustan Syringes & Medical Devices Ltd who has recently participated in the trial.

“That’s fair, considering we took the risk of being part of a clinical trial. For me, it’s okay if the vaccination centres use this as an incentive to drive volunteers for clinical trials,” he added.

‘Document should be taken in the right spirit’ 

Principal investigator Dr Venkat Rao of the Odisha-based Institute of Medical Sciences, a Covaxin trial site, said the document should be taken in the right spirit. 

“There was a discussion on conference call about the common concern raised by trial participants that, when the legit vaccine will be launched by the government, the participants won’t be able to take that (if they have taken the trial vaccine),” he added. “As a fallout of the discussion, this FAQ was added.” 

He said the document explains to people that “first, the vaccine will be given to different groups. Your turn might come slighter later”. 

“It’s not about influencing the participants. We all know that rolling out of the vaccines is a difficult process. When two people participate in the trial, it is likely that at least one of them will get the vaccine, if the other is getting placebo. It is better to get something than nothing,” he added.

At Aligarh Muslim University’s Department of Tuberculosis and Respiratory Diseases, another trial site, Dr Mohammad Shameem disagreed. 

“The study is a double-blind study. I don’t get to know who is getting the vaccine and who is getting the placebo. So, how can I tell the participant that they might get protected against Covid?”

However, he added that the FAQ didn’t apply to AMU since it had already recruited its targeted 1,000 participants.

Also Read: Vaccines are cleared based on risk-benefit ratio, so keep faith — govt on Bharat Biotech shot


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