Controversy followed close on the heels of a recent study on the long-term safety of Covaxin, the Covid-19 vaccine developed by Bharat Biotech in collaboration with the ICMR-NIV. The paper authored by researchers Upinder Kaur, Aakansha Jaiswal, Ayushi Jaiswal, Sankha Shubhra Chakrabarti, and others from the Banaras Hindu University (BHU) was published in Drug Safety, the official journal of the International Society of Pharmacovigilance. However, ICMR (Indian Council of Medical Research) demanded its retraction as it was a ‘poorly designed study’. This garnered media attention, prompting editor Nitin Joshi to oblige, thereby setting a bad precedent and letting down the community of scientists.
The study on Covaxin included a one year follow up on vaccinated individuals to collect data on Adverse Events of Special Interest (AESI). Researchers found that of the 926 respondents, over 40% reported viral upper respiratory tract infections, while new-onset skin and subcutaneous disorders and general disorders were reported in around 10% of individuals. Nervous system disorders were reported in 4.7%. The full text of the study included its limitations and highlighted the need for more detailed research.
ICMR found the study unacceptable as it was poorly designed and had no control arm of unvaccinated individuals to compare the rates of events between the vaccinated and unvaccinated groups. As the method of data collection used had a high risk of bias, the reported events in the study could not be attributed to Covid-19 vaccination.
In the retraction notice, the editor said that he no longer had confidence in the study’s conclusions as the data were presented in a way that could lead to “ambiguous or incorrect interpretations” and that the study “should be removed on public health grounds”.
The editor’s comments in the notice are questionable, as none of these concerns were raised before its publication on May 13, 2024. In fact, it was the editor and two independent reviewers who reviewed the study. The authors revised the text as per the changes suggested by the reviewers.
Why did the editor publish the paper if it had serious flaws? When the editor said that he has lost confidence in the scientists who conducted the study, it is the scientific community that lost confidence in the editor.
Similar paper on Covishield not retracted
Interestingly, ICMR’s critical remarks apply equally well to another study by BHU researchers published in the same journal a year ago — a paper on the safety of Covishield, the Covid-19 vaccine developed by Oxford-AstraZeneca, published on May 3, 2023. Its results were similar to those of the Covaxin study, however, the numbers of different adverse events were smaller. Researchers found that vaccination using Covishield received after recovery from Covid-19 is an independent risk factor for AESIs and persistent AESIs.
Some of the researchers who had worked on the Covishield study worked on the Covaxin study as well.
However, ICMR did not call for the retraction of this study even though it had all the telling ‘frailties’ of the Covaxin safety study. Was its retraction not demanded because the study did not create a controversy?
If statements from such studies that use the Cohort Event Monitoring method are taken out of context and blown disproportionately, they can become controversial.
Both studies followed the Cohort Event Monitoring (CEM) method, an intensive method of post marketing surveillance for medicine safety to collect and analyse data, endorsed by the World Health Organisation (WHO). According to WHO, AESIs mean “a pre-specified medically-significant event that has the potential to be causally associated with a vaccine product that needs to be carefully monitored and confirmed by further special studies.” Once such special studies are conducted, the noted AESI may ultimately be found to have no direct connection to the vaccine itself.
The CEM method merely gives warning signals. The identification of AESIs does not denote anything concrete; however, there is a requirement for further studies to resolve such identified AESIs. The researchers are duty-bound to report the observed findings as per the scientific process. However, was it appropriate for the researchers to carry out detailed analysis of the collected data in both papers?
The peer reviewers and the editor knew what was the due process and did not find any shortcomings in both papers, and published them. One of them – the one on Covaxin – unfortunately courted controversy.
Even so, the editor was duty-bound to refer the paper to an independent committee to decide its fate rather than exonerating himself and the peer reviewers for their indefensible action. The editor and publisher chose the convenient path and removed the paper, as they did not want to leave any ‘ugly debris’ behind. One can’t help but observe that the gatekeepers of Drug Safety failed.
Travails of peer reviewing
It is quite ironic that the same editor had co-authored an editorial on March 8 this year on the many issues they face regarding peer reviewing. They wrote, “The process of peer review represents the gold standard for evaluating medical science across journals and disciplines and is considered a key pillar to ensure reliable research, scientific integrity, timely dissemination of information, and ultimately, better patient care. However, the current process is far from perfect (example: lack of standardisation, relatively slow pace), subjective (example: susceptible to conscious and unconscious bias) and does not seem ideally suited to tackling the new challenges, especially those posed by the growing number of scientific journals and preprint services containing manuscripts that are not yet peer reviewed or accepted by academic journals.”
Considering the paucity of good reviewers, it should be enquired whether the peer reviewers were the same for both the Covishield and Covaxin papers.
ICMR’s flawed response
Over a century old, ICMR, the premier research development agency of the country collaborated with Bharat Biotech to develop and produce India’s own vaccine against Covid-19, a creditably proud national achievement.
However, the ICMR’s approach in handling the controversy surrounding the BHU study is far from desirable.
It particularly exaggerated what was possibly an administrative lapse or indiscretion of a researcher in acknowledging ICMR’s non-existing ‘contribution’ to the study. The acknowledgement in the now removed paper read, “Upinder Kaur and Sankha Shubhra Chakrabarti thank the Institutions of Eminence Scheme in the Banaras Hindu University for research support. Sankha Shubhra Chakrabarti thanks the Indian Council of Medical Research for research support. (sic)”
The ICMR threatened legal and administrative action against the two authors, when only one author made the allegedly ‘grave’ mistake. ICMR’s action of issuing the letter to both of them and circulating copies to the press was unfair, faulty, and indefensible.
Can we appreciate the alacrity with which ICMR responded to the controversial paper? Yes and no!
One reason for the media to go to town was the adversarial reactions of the BHU, ICMR, and Bharat Biotech. Even though BHU faithfully followed the WHO recommended CEM method, Bharat Biotech went ahead with a defamation suit against the researchers.
Engaging in turf war, the ICMR lost a golden opportunity to raise vaccine awareness among the public. As vaccine denial is a reality, ICMR could have used the opportunity to raise awareness on the benefits of vaccination by giving quantitative data on vaccine safety.
More importantly, the ICMR-Bharat Biotech collaboration must expressly publish the results of phase 3 study of Covaxin to boost public trust and bolster the credibility of the agencies.
Due to the unprecedented health crisis caused by the Covid-19 pandemic, the competent regulatory authority had granted Emergency Use Authorization (EUA) to Covaxin manufacturers, allowing them to use vaccines to prevent and/or reduce the impact of life threatening effects of Covid-19. Such granting of EUA is done after assessing the available clinical trial data, and not the entire trials. The developers/manufacturers parallelly continue to do other clinical trials to obtain additional safety and effectiveness information to enable full license.
Regrettably, ICMR’s priority appears to be to discipline the BHU researchers. The community of scientists, certainly the younger generation, may sympathise with the researchers who now face a defamation suit.
The need for a science media centre
How and why did this paper get wide media coverage? Reporters with a few exceptions carried verbatim a few statements from the abstract of the paper as they were ‘newsy’. Few sought guidance from any expert. The reports of those who did were balanced.
What most of the media failed to recognise is that the abstract does not constitute the whole paper. The authors did elaborate the limitations of their study prominently in the paper. However, they should have explained them in simple terms in the abstract as well and showed healthy scepticism about their own results. Scientific temper demands that. A conscious and balanced approach may have reduced the chance of misinformation and misinterpretation.
The controversy surrounding the Covaxin study points to the need for a science media centre (SMC) like the one in London. It ensures that the press has ready access to experts’ views whenever journals publish notable papers.
Dr K S Parthasarathy is a former secretary of the Atomic Energy Regulatory Board. He is available at ksparth@yahoo.co.uk to receive feedback.
Views expressed are the author’s own.