Four days after India’s first indigenous vaccine candidate for Covid-19 was granted approval for human clinical trials by the drug regulator, the Indian Council of Medical Research on Thursday said that it wanted to “launch the vaccine for public health use latest by August 15”.

On July 2, the council’s director-general Balram Bhargava wrote to the 12 institutions participating in the trial to “fast-track all approvals”, adding that participants on whom the vaccine would be tested should be enrolled “no later than July 7”.

“Non-compliance will be viewed very seriously,” the letter warned, adding that the vaccine was “the top-most priority” of the government.

The vaccine candidate, named Covaxin, has been jointly developed by the Hyderabad-based private company Bharat Biotech and the ICMR. It was approved for human trial on June 29. In effect, the ICMR is saying it would release a vaccine for human use in less than two months of it being approved for trial – a timeline unheard of anywhere in the world.

Independent experts have criticised the letter. “I don’t think anywhere in the world has anyone ever given a date in advance for the release of a new vaccine before a clinical trial has even begun,” said Amar Jesani, editor of the Indian Journal of Medical Ethics and a public health activist. “That is not how science works.”

Vasantha Muthuswamy, chairperson of the ethics advisory committee of the ICMR’s bioethics cell, said she had not seen Bhargava’s letter, but conceded the timelines were too short. “By general experience, a month to decide whether to release a vaccine is a very short time,” she said. “Even if you fast-track it, it will take a minimum of one year.”

Strikingly, the expected duration of the trial, according to the government’s official clinical trial registry, is one year and three months.

Even many doctors entrusted with conducting the trial told the timelines laid down in the ICMR letter were unrealistic.

‘This is a trial on humans not animals’

For starters, seven of the 12 participating institutes are yet to receive a green-signal from independent ethics committees, a prerequisite for conducting clinical trials.

“As a principal investigator, I would not move unless I get a clearance, let it be anyone who is telling,” said Venkata Rao, in charge of the trial at the Institute of Medical Sciences and SUM Hospital in Odisha, one of the 12 chosen sites.

Rao added: “It is not that I am being adamant, but I am humbly saying that we should follow the principles. And the first and the most important principle is: do no harm.”

Another principal investigator at one of the government institutes chosen for the trial was even more scathing. “That is not a scientific letter,” said the doctor, referring to ICMR’s correspondence. “If the ethics committee does not approve, forget July 7 enrolment, we can’t do it by December 7 also even if the PM [prime minister] intervenes. We cannot deviate from protocols – this is a trial on humans not animals.”

Prime Minister Narendra Modi at a meeting on June 30 to discuss the development of a vaccine against the coronavirus. Credit: PTI

Lucknow’s King George Hospital is also awaiting a green signal from its ethics committee. “If they agree, we will be part of the trial and if they don’t we can’t be part of it,” said R Vasudev, the principal investigator of the trial at the hospital.

Jesani said it beat him that “the director general of the ICMR can write a letter like this”. “The head of the institution can call an ethics committee meeting at best, but how can you ask for speedy approvals and put in an implicit threat when ICMR’s own guidelines say that the ethics committee should be independent of the administration?” asked Jesani.

Among the five participating institutions that have already got clearances from their ethics committee, four are private hospitals. All four got the approval on June 30 itself, a day after the trials were allowed by the drug controller.

One such institute is the Jeevan Rekha Hospital in Karnataka’s Belgaum. The hospital’s administrators seemed quite upbeat about meeting the government’s deadline. “By August 15, we hope everything will be in place, I am not saying 110% but 99%,” said an administrator of the hospital. “If the government has set a date, they must have thought something about it.”

The three phases of clinical trials

But other institutions questioned the timelines. For one, enrolment of participants by July 7 was not possible under any circumstances, said Vasudev of Lucknow’s King George Hospital. “If at all, we will get approval [from the ethics committee] by then.”

Even if the trial was approved by July 7, it would still be difficult to furnish the final results of the trial by August 15, he added. “The sample size we have been allotted is around 150-200. We should be able to manage that by August 15, but the results would take some more time.”

Across the 12 centres, the trials are envisioned to have a sample size of 1,125 people.

As detailed in the registry, the trials would combine Phase 1 and Phase 2, a practice that is being followed in several clinical trials of probable Covid-19 vaccine candidates to expedite the process.

Phase 1 of a clinical trial is usually small and is used to determine its safety profile. Phase 2, on the other hand, employs a bigger sample size, and looks at the immune responses triggered by the vaccine.

However, a vaccine is deemed safe to be commercially available only after Phase 3 – a much larger efficacy trial involving thousands of participants.

The trial document for Covaxin does not mention Phase 3. Even for Phase 1 and Phase 2, there appears to be some confusion over the sequence to be followed.

While Vasudev of Lucknow’s King George Hospital said he had been sent the protocol for only Phase 2 trials, Rao of the Institute of Medical Sciences and SUM Hospital in Odisha said his organisation would be starting with Phase 1. “Then we will be migrating to Phase 2, but that process is not clear yet.”

The lead investigator at the government hospital was blunt in his assessment. “By August 15, even Phase 1 will not be complete,” he said, before quipping, “I think they got the date right, but forgot to add the year as 2021.”

This reporting was supported by a grant from the Thakur Family Foundation. Thakur Family Foundation has not exercised any editorial control over the contents of this article.