Indian Council of Medical research suggests a month’s time to complete three phases, global experiments taking months
A letter written by Indian Council of Medical Research (ICMR) Director-General Balram Bhargava stirred a lot of interest on the morning of July 3, 2020 — it claimed that the first Indian indigenous vaccine against COVID-19 would be available for public use by August 15. The vaccine, Covaxin, is manufactured by Hyderabad-based Bharat Biotech International Ltd.
However, as the day progressed, not just independent experts but even investigators of the clinical trial, including the principal investigator, said it was not possible in any way.
Twelve hospitals and institutes have been selected across India for conducting the clinical trials. Down To Earth (DTE) spoke to a couple of investigators at these trial sites.
When DTE called a senior faculty member of one of the institutes referred to in Bhargava’s letter, he was in total disbelief. “I am sure ICMR does not mean that we should complete trials by August 15,” he said.
“The letter must have inadvertently expressed something different from what they meant. This is just impossible,” the member, who requested anonymity, added.
Another investigator, Venkata Rao, from the Institute of Medical Sciences and SUM Hospital, Odisha said: “If I make a wild guess, since multiple sites are involved, we may do simultaneous Phase I and II trials at different sites. Only they can be completed by August 15. How can the remaining be completed by this date can only be decided after a discussion with ICMR.”
When asked if he was under pressure by ICMR to complete the project within the stipulated time frame, he mentioned that the first principle of any trial was to ensure no harm to the study participant. “No amount of pressure will work on us to ensure that the ethics of trial are not compromised,” he said.
What ICMR’s letter said
The letter by Bhargava, on the other hand, was what some experts described as dictatorial. “Kindly note that non-compliance will be viewed very seriously. Therefore, you are advised to treat this project on highest priority and meet the given timelines without any lapse.” The letter also asked these institutes to “fast track all approvals.”
SP Kalantri, medical superintendent at the Mahatma Gandhi Institute for Medical Sciences in Sevagram, who specialises in clinical research, said, “These are arm-twisting tactics.”
Before commencement of a clinical trial at any hospital, its institutional ethics committee (IEC) has to give an approval to that effect. After the study participants are enrolled, the IEC goes through the study protocol, does risk-benefit analysis and looks into the profile of participants, studies their consent form etc.
“The IECs are being pressured to give approvals without having adequate time to do all of this and fast track the process. This is a serious compromise,” Kalantri said.
Incidentally, Bhargava has asked all institutions to initiate recruitment of participants no later than by July 7. On the other hand, according to details available at the Central Trial Registry of India, a government platform where all trials are registered, the recruitment has to begin by July 13.
Nonetheless, one of the investigators whom DTE spoke to and referred to above, said, “We will begin the recruitment process by July 7 and end it in a week.”
Missing pre-clinical data
Before the initiation of three-phase human trials, animal studies are done in labs to have pre-clinical data. This is important because trial protocols are decided on its basis.
However, it is not available in the public domain yet. So much so that one of the investigators whom DTE spoke to revealed that even he had no access to this data.
“All that we have been told is that there were no adverse effects of the drugs in animal models. I have not seen discrete data,” he said.
DTE called up Bharat Biotech spokesperson Sheela Panicker to know the pre-clinical data. She refused to share it. As for the ICMR letter, a copy of which has been also marked to the firm, she said she could not even confirm whether the letter was received or not.
“This is very strange. When you are trying to produce the world’s fastest vaccine ever, you should at least share the pre-clinical data in an open public platform. Bharat Biotech must do this because they are using a genome that is sequenced by ICMR’s National Institute of Virology. If it is not doing so, at least ICMR must do it,” Anant Bhan, a bioethics expert said.
“This is the shortest-ever timeline of vaccine development I have ever heard of. To say the least, it sounds extremely worrisome and unrealistic,” Amar Jesani, an independent expert in bioethics and public health, told DTE.
“After conducting Phase I and Phase II trials, one analyses data, which can take anything from a few weeks to months and the protocol for the third phase of the trial is prepared. ICMR seems to be doing this at super human speed. If you compare it with other COVID-19 vaccines which are being developed globally, you will realise the absurdity of it,” Jesani said.
He also said the expert committee in the Central Drugs Standard Control Organisation office must have thoroughly gone through the study protocols before giving a go-ahead for the trial. A three-level review is done there. At least it should ensure transparency and make those reviews public.
After pre-clinical studies are completed on animal models, a vaccine candidate has to go through three phases of human trial.
In the first phase, the healthy volunteers are given the vaccine to study the tolerance against the toxicity of the vaccine. If the study participants tolerate it, the results are positive.
In the second phase, immunogenicity of the vaccine is tested, that is whether it is able to initiate an immune response against the virus in the study participant.
The third phase is to study the efficacy of the vaccine in the field. Usually thousands of study participants are enrolled across different cities to see in what proportion the vaccine proved to be efficacious. A vaccine is generally considered successful if it has worked well in more than 50 per cent patients.
How other COVID-19 vaccines fare?
The only vaccine to proceed into Phase III trials is that of Oxford University. It announced the Phase 1 trial way back on March 23. In a press statement on April 2, it said it would take at least 12-18 months to develop this new vaccine.
Another vaccine of US-based firm Moderna Inc has completed two phases of trials with the National Institute of Health. It is all set to launch Phase III with 30,000 participants this month.
A look at the timeline of this vaccine reveals that it disclosed its intent to run a Phase I trial way back on January 23. It took almost four months for it to announce Phase I results
A vaccine candidate of Chinese firm Sinovac Biotech Ltd on June 13 announced that its Phase I and II trials had been successful and it was ready to go into the third phase. Its vaccine development commenced at the end of January 2020.
DTE dialled the ICMR D-G and other officials to understand how the body proposes to complete all three phases in little over a month’s time for which others took quite a few months. Neither Bhargava nor others responded.
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