New Delhi: A day after a US publication claimed that documents show how Bharat Biotech made “questionable changes” to trial protocols and omitted the data of several participants in the race to develop the homegrown Covid vaccine Covaxin, the Union Health Ministry has rubbished the allegations as “misleading, fallacious, and ill-informed”.
Citing numerous internal documents, which ThePrint has also seen, the report by STAT News said that Hyderabad-based pharma company Bharat Biotech took various shortcuts in the processes for testing the safety and efficacy of Covaxin to “expedite the approval process” for the vaccine. STAT News is produced by Boston Globe Media and focuses on medical journalism.
The report also suggested that the Central Drugs Standard Control Organisation (CDSCO), which is India’s drug regulator, did not do due diligence in approving the vaccine.
Bharat Biotech has hit back at the allegations in a strongly worded statement. Calling the report “incorrect and erroneous”, it said that every decision during the process was taken in public interest to bring the vaccine in the middle of the pandemic. It also pointed a finger at “select few individuals and groups” who “helped perpetuate fake news” throughout the pandemic.
Meanwhile, the Health Ministry has asserted in its own statement Thursday that the Government of India as well as CDSCO “followed a scientific approach and prescribed norms in approving the Covid-19 vaccines for emergency use authorisation”.
Here is a look at what the internal documents cited in the news report show, as well as Bharat Biotech’s reactions to the allegations.
Also read: CBI chargesheet in Biocon case raises questions about how India manages drug trials
‘Discrepancies’ in trial participants
One of the “discrepancies” flagged in the STAT report was that the number of people enrolled in the Phase I portion of the trial differed from what was later published in the international medical journal The Lancet.
Initially, documents dated 2 September 2020 reveal that the Phase I/II protocol had 402 participants who were given the first dose, while 394 subjects got the second dose.
However, when the results of the said trials were published on 21 January last year in Lancet Infectious Diseases, the paper stated that 375 people were given the first dose and 368 received the second.
This raises questions because in clinical trials, data should not be omitted from any of the patients included in the study in order to keep the results unbiased.
According to STAT News, Bharat Biotech director V. Krishna Mohan “conceded the error” but said that although there were some mistakes, the decisions reflected the unusual challenges of working amid the pandemic.
Mohan reportedly attributed the discrepancies in the data to communication gaps that resulted from multiple teams across the country working at breakneck speed.
“Perhaps, we could have disclosed it,” Mohan was quoted as saying by STAT News. “It was not so much a discrepancy. … The whole idea was, ‘Let’s get the data out.’”
Changes to trial protocols require the approval of an Institutional Review Board (IRB) or the Independent Ethics Committee (IEC). Mohan said that the Drugs Controller General of India was informed of the change in the number of participants.
While documents reveal that the trials were supposed to be an “adaptive, seamless study” — which means changes to protocols could be carried out — there were no disclosures about the changes in the studies that were later published.
Changes to trial protocols
Internal documents reveal that major changes were made to the Phase II trial protocols, or set of procedures, to test the vaccine’s efficacy and safety.
The initial trial protocol dated 17 August 2020 was set to have three trial groups or arms. Two groups of 300 participants each were supposed to receive the vaccine in different doses, while the third group would have been the control group that receives a placebo.
Having a control group is a standard procedure in any clinical trial as it helps rule out any biases in the study design. This group helps researchers collect data on what happens when participants do not receive a drug in the controlled setting.
However, in the amended trial protocol data as of 2 September 2020, the number of participants were reduced to 190 in the first two groups, while the control group was done away with altogether.
The reason mentioned for doing so in these documents was to expedite the trial, as the world was facing a pandemic and India was still in need of a vaccine.
Moreover, the approval for Phase III trials was given on 10 October 2020, before the Phase II trials were completed, documents accessed by ThePrint show.
What has Bharat Biotech said?
According to the STAT News article, Bharat Biotech executives had acknowledged that they were under “political pressure” and were focused on releasing the vaccine as soon as possible.
In a statement after the article was published, however, Bharat Biotech raised strong objections to how it had been characterised.
“There was no external pressure to accelerate development… The pressure was all internal to develop a safe and effective vaccine for the Covid-19 pandemic, to save lives and livelihoods in India and globally,” the statement said.
It added that hundreds of millions of doses of Covaxin had been administered worldwide and that the vaccine had an “excellent safety record with minimal adverse events”.
The statement also elaborated at length on how the company had conducted clinical studies and developed the vaccine in accordance with global guidelines. It said that “more than 20 publications” had documented “every aspect” of the vaccine’s development.
On allegations around trial protocols, the statement said that Covaxin was evaluated in about “20 pre-clinical studies, including three challenge trials (in animals) and nine human clinical studies”.
“These trials have clearly demonstrated safety and efficacy of Covaxin,” it noted.
The statement reserved scathing words for those who it claimed were trying to “discredit” the work of Bharat Biotech.
“Vaccines against ebola and monkey pox, were approved by stringent regulatory agencies in developed countries based on Phase I and II clinical data only and without Phase III data. If such an approval was given by regulators in India, there would be an uproar, but the same people and organisations remain silent, demonstrating their hypocrisy,” the statement said.
“We condemn the targeted narrative against COVAXIN put forth by a select few individuals and groups who have no expertise in vaccines or vaccinology. It is well known that they helped perpetuate misinformation and fake news throughout the pandemic. They are unable to comprehend global product development and licensure processes,” it added.
“While these people and organisations were busy with false information and fake news during the pandemic, more than 1,000 personnel at Bharat Biotech across India were busy developing, testing, manufacturing, and distributing Covaxin”.
(Edited by Asavari Singh)
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