Why COVID vaccine safety needs scrutiny | Explained

A health worker displays empty vials of Covaxin in Guwahati. File
| Photo Credit: AP

The story so far: The Indian Council for Medical Research (ICMR) issued a letter to the researchers of Banaras Hindu University last week, countering their study on the side effects of India’s indigenous vaccine for COVID — Covaxin. In a rejoinder sent a couple of days after the publication of the research paper in a peer-reviewed journal, ICMR head Rajiv Bahl claimed that his institution had been incorrectly and misleadingly acknowledged in the paper. He pointed out what he called ‘critical flaws’ in the ‘poorly-designed study’. Notably, the ICMR was involved in developing Covaxin along with Bharat Biotech.

What did the BHU study conclude?

Adolescent girls and those with co-morbidities were at a higher risk of adverse events after receiving Bharat Biotech’s BBV152 (Covaxin) vaccine against COVID-19, BHU researchers said. Nearly a third of the participants reported adverse events of special interest (AESI). The one-year observational, follow-up study titled ‘Long-term safety analysis of the BBV152 coronavirus vaccine [Covaxin] in adolescents and adults: Findings from a one-year prospective study in North India’, also said that serious adverse events occurred in 1% of BBV152 recipients, and that extended surveillance is warranted following the vaccine administration.

Viral upper respiratory tract infections were reported in 47.9% adolescents and 42.6% adults, as per the study. New onset skin and subcutaneous disorders, general disorders, and nervous system disorders were the common AESIs in adolescents. General disorders, musculoskeletal disorders, and nervous system disorders were the common AESIs in adults. Menstrual abnormalities were noticed in 4.6% of female participants. Ocular abnormalities and hypothyroidism were observed in 2.7% and 0.6% of the participants, respectively. Among the serious AESIs (1%), stroke and Guillain-Barre syndrome were identified in 0.3% and 0.1% of the participants, respectively.

In response to this, Bharat Biotech, the vaccine manufacturer which worked with the ICMR’s own National Institute of Virology to develop the vaccine candidate, said for such a study in safety to be effective and informative, and for it to avoid investigator bias, some data points were also required. This included the AESI safety profile of the subjects prior to their participation in the study; a comparison of the safety profile of non-vaccinated subjects during the course of the study; a comparison of the safety profile of subjects who received other vaccines during the course of the study etc.

What did ICMR object to?

In his letter, Dr. Bahl said ICMR was not associated with the study and had not provided any financial or technical support. He alleged that the authors had acknowledged ICMR for research support without prior approval or intimation to the institution, calling this “inappropriate and unacceptable.”

With reference to the study itself, he claimed there were critical flaws: the study had no control arm of unvaccinated individuals for comparison with the vaccinated group, and therefore, the reported events in the study cannot be linked or attributed to COVID-19 vaccination; it did not provide background rates of patterns observed in the general population, and thereby made it impossible to study the observed events in the post vaccination period. Further, Dr. Bahl claimed there was no baseline information of study participants; the study tool was inconsistent with the AESI as defined in the reference paper, and the method of data collection (participants were contacted over the telephone, and their responses recorded without any clinical confirmation).

He further asked the researchers to remove the acknowledgement to ICMR and publish an erratum. His letter also called to retract the paper, with a remark: “This paper implicitly makes conclusions about vaccine safety that are not supported by evidence.” The BHU recorded that it had received the communique addressed to its researchers. The researchers have communicated their responses to the ICMR.

What was the fallout?

Most researchers were shocked by the response of the ICMR, terming it as “academic censorship.” Multiple accounts of doctors and researchers on social media also pointed out that the ICMR developed the vaccine along with the company, and not declaring its vested interest was also a serious lapse in research terms. Among those who formulated an official response, foremost was the Universal Health Organisation (UHO), a group of researchers, doctors, and public health experts, who echoed the research ecosystem’s shock at the belated denial. The UHO wrote an open letter to the ICMR stating the study filled a key gap in terms of field data, analysing the safety of Covaxin.

“While we were hoping and expecting that the ICMR would build upon this study, address its shortcomings, and elevate the standards of vaccine safety, we are aghast to come across letters sent by ICMR asking for the retraction of the paper, and threatening the authors of the study,” it said. On the point of not having a control group, the letter said, it was indeed a shortcoming but had been admitted in the study itself. Besides, this actually points to the fact that it was the ICMR that has access to the data with the control group — the original phase 3 trials of Covaxin. Neither the ICMR nor the company had published the long-term safety trials, it charged. While using telephonic interviews was not ideal, it has been used by ICMR in the past, even in papers on COVID vaccines. To call for the retraction of the BHU paper on these lines was unbecoming of a scientific institution of ICMR’s stature, the letter added.