COVAXIN controversy: Doctors in trial sites chosen by ICMR say human trials can’t be fast forwarded, anticipate 6-month observation period
Hyderabad-based Bharat Biotech received approval from the Central Drugs Standard Control Organisation (CDSCO) to begin human trials of COVAXIN last week. The vaccine has been developed in collaboration with the ICMR and National Institute of Virology in Pune.
The hospitals chosen by the ICMR to conduct human trials of the coronavirus vaccine developed by Bharat Biotech — COVAXIN — are gearing up for the "top priority project" and looking at a span of at least six months of monitoring the people who will be administered the vaccine. Hyderabad-based Bharat Biotech received approval from the Central Drugs Standard Control Organisation (CDSCO) to begin human trials of COVAXIN last week. The vaccine has been developed in collaboration with the ICMR and National Institute of Virology in Pune.
Following the approval for human trials, ICMR chose 12 institutes as 'clinical trial sites' to conduct the trials of the vaccine on chosen participants.
Dr Chandrashekhar Gillurkar, director of the Gillurkar Multispecialty Hospital in Nagpur, is anticipating an observation period of at least six months for the people who will be administered the trial vaccine. His hospital is one of the 12 trial sites chosen to conduct human trials.
Explaining the medical timeline of Phase I and Phase II trials, he said that the research team will check in with the ‘participants’ of the trials on day 14, day 28, day 42, day 104, and day 194 after the vaccine is administered.
The timeline, laid out by Dr Gillurkar, becomes significant after a letter, circulated internally by the ICMR, instructed trial sites that the vaccine should be launched for public use by 15 August. The letter, dated 2 July, also said, “In view of the public health emergency due to COVID-19 pandemic and the urgency to launch the vaccine, you are strictly advised to fast track all approvals related to initiation of the clinical trial and ensure that the subject enrollment is initiated no later than 7 July, 2020... Non-compliance will be viewed very seriously," the letter further added.
'Human trials can't be fast-forwarded'
A consultant physician with Jeevan Rekha Hospital in Karnataka’s Belgaum, another hospital listed as one of the trial sites by the ICMR, Dr Amit Bhate said that making the vaccine available for public by 15 August “is not possible”. The hospital will have to follow scientific protocol regardless of the instruction in the "leaked" letter, he told Firstpost.
“It’s a slow process, human trials can’t be fast forwarded. There are many dynamic factors to be taken into account in vaccine research, nothing can be hurried just because there is a deadline set,” Bhate said, "We haven’t personally received any instruction about making the vaccine available for public use by 15 August, so we will continue to follow scientific methods in our research."
Dr G Arjuna of the King George Hospital in Andhra Pradesh’s Visakhapatnam, one of the 12 sites picked by the ICMR. echoed Bhate’s statement. “Arbitrarily they (ICMR) have chosen one date, but this is a scientific process so we can’t pre-decide a date for the launch of the vaccine," he said.
According to Gillurkar, by 15 August only the initial results from Phase I and Phase II trials will be available. He said that the government will get an initial idea of the safety and immunogenicity (ability of a foreign substance to provoke an immune response in the human body) of the vaccine by then. “It is up to the discretion of the government then, whether to release the vaccine to the public or not,” Gillurkar said.
The ICMR's letter had sparked off a heated debate among the medical community who slammed the research body for unprecedented speeding up of the process. Speaking to Firstpost, Dr Anant Bhan, a researcher in global health, bioethics and health policy said, “It’s understandable for a pandemic of this scale. But we can’t compromise on the safety and the efficacy aspects. Minimum standards around safety, efficacy and quality need to be followed. Collapsing the entire process to just 45 days is unlikely, and almost impossible,” he said.
The ICMR, on 4 July , clarified that it is adhering to global standards in developing and testing the vaccine. "Our process to develop vaccine to fight COVID-19 pandemic is as per globally accepted norms of fast tracking," ICMR said.
What to expect during clinical trials of COVID-19 vaccine?
Of the 12 sites listed, the three hospitals that Firstpost spoke to - Gillurkar Multispecialty Hospital in Nagpur, King George Hospital in Visakhapatnam and the Jeevan Rekha Hospital in Belgaum - have worked on vaccine research in the past.
Gillurkar said his hospital had worked with Bharat Biotech on more than 10 research projects and Bhate said the Belgaum hospital had already been conducting research on the typhoid vaccine, among others. The doctors said that the ICMR has stipulated that hospitals must screen people from ages 18 to 55 and only recruit those who are completely healthy and without co-morbidity. The screening process that is set to begin on 7 July.
"The ICMR has said that in phase I, a total of 375 people should be administered the vaccine and 750 in in phase II. We have also been instructed to administer a low dose to the participants in the first phase," Gillurkar said. All the information on the condition of the participants after administering the vaccine will be shared with the ICMR, Bhate told Firstpost.
Gillurkar said monitoring the level of anti-bodies in the patient will be an important metric to understand whether the vaccine is working. "We will observe basic parameters in phase I and phase II, if there is a significant rise in the level of anti-bodies, then the vaccine is working," he said. Participants could also experience itching or swelling around the area of the injection, or even nausea, body ache, or fever. In very rare cases, there have been instances of anaphylactic shock (an extreme, often life-threatening allergic reaction to an antigen to which the body has become hypersensitive). "But that is very rare because the vaccine basically contains a ‘killed virus’," Gillurkar added.
Discrepancies emerge in the information given by ICMR
The doctors from the three hospitals told Firstpost that the information from the ICMR was not clear enough to understand the process of the trial properly. While Gillurkar from Nagpur said that the results of the pre-clinical trials that were conducted "in New Zealand on rabbits and mice" by Bharat Biotech had been shared with his hospital, Bhate and Arjuna said that they had not received any such information.
Gillurkar also said that he had received the ICMR’s letter specifying the 15 August date for the launch of the vaccine while Bhate said his hospital had not. Arjuna, from King George Hospital, also said that he hadn’t received instructions on the recruitment of participants for the trials while the others had. Other media reports also noted the discrepancies in sharing information.
Arjuna further added that his hospital was also consulting with the Andhra Pradesh government and was likely to hold a meeting with the state health department in the coming days. "We are taking the guidelines given by three authorities – ICMR, the state government, and our ethics committee – into consideration before we start the trials," he said.
Currently, the hospital was awaiting approval from the state government and the ethics committee. “The ethics committee will give approval quickly because it is a government project and not private,” he said.
Bharat Biotech recently said it has submitted all data pertaining to Covaxin to the WHO for EUL and is awaiting feedback from the global health watchdog
More than 4.49 crore (4,49,03,025) balance and unutilised COVID-19 vaccine doses are still available with the states and UTs to be administered, the ministry said.
Over 4.23 crore balance and unutilised vaccine doses are still available with the states and Union Territories for inoculation, it said.