Serum Institute’s trial has run into a controversy. Will this erode public trust in a vaccine?


If the news was all Covid-19-related doom and gloom for the better part of 2020, the last couple of weeks have been awash with optimistic headlines. Several vaccine candidates have been reported to show potential that exceeds expectations.

India has not been immune to this excitement. The Oxford-AstraZeneca vaccine that the country is betting on for the early rounds of immunisation has shown fairly promising results too.

The Pune-based Serum Institute of India, which is the world’s largest vaccine manufacturer,has tied up with the University of Oxford and the British-Swedish company AstraZeneca to commercially produce and market this vaccine in India if and when it is approved.

But allegations that surfaced late last week concerning possible side-effects of this vaccine may have punctured some of the initial euphoria. Public health activists say that the seeming lack of transparency that they believe the episode reflects could result in public distrust and hurt India’s efforts to inoculate people.

An explosive allegation

The controversy began when a volunteer from Chennai who had participated in the vaccine’s trial went public with a threat to sue Serum India Institute, the Pune-based company that is conducting trials on the vaccine in India.

The person’s lawyer and family alleged he had suffered serious neurological impairment after the under-trial coronavirus vaccine was administered to him. In a legal notice sent to Serum Institute, the person reportedly warned of legal action if the company did not halt the vaccine’s trial immediately and suspended all plans for its “manufacture and distribution”.

Serum Institute was quick to defend the trial. It described the allegations as “malicious and misconceived” and threatened to sue the volunteer. “The complications he suffered were independent of the vaccine trial he underwent,” the company said in a statement. In other words, the person did not fall sick because of the vaccine, according to the company.

The principal investigator of the Chennai leg of the trials also came on record saying that he had concluded that the adverse event was unrelated to the vaccine, an assessment that he said was corroborated by the ethics committee of the facility where the trials are taking place, and the Data and Safety Monitoring Board of the Serum Institute.

‘Blatant attempt at intimidation’

Despite this, the company’s threat to counter-sue the volunteer caused outrage among India’s public health and scientific communities. They said that an allegation like that called for transparency, not high-handedness. The “blatant attempt at intimidation of a clinical trial participant” was an attempt by Serum Institute to “divert public scrutiny of its trial”, said the AlI India Drug Action Network, a watchdog organisation, in a statement.

Equally alarming, critics said, was the way the episode came to light: only after a volunteer threatened to go to court. This was in stark contrast to how adverse events in the same vaccine’s trials were handled in other parts of the world.

Apart from the Chennai case, there have been two other instances of volunteers reporting severe adverse events (requiring hospitalisation) during trials of the Oxford-AstraZeneca vaccine. Both times, the trials were globally paused – and a public announcement made to that effect – until it was concluded that the illnesses had not been caused by the vaccine.

A scientist at Serum Institute’s Pune facility in May. Credit: Euan Rocha/ Reuters

‘To safeguard the reputation of the company’

In the face of mounting criticism, Serum Institute issued another statement on December 1, defending its actopms. While they were “sympathetic with the volunteer’s medical condition”, the company said it sent the legal notice “to safeguard the reputation of the company which is being unfairly maligned”.

The statement further reiterated that “regulatory and ethical processes and guidelines were [being] followed diligently and strictly”.

It said:

The concerned authorities were informed and the Principal Investigator, DSMB [Data and Safety Monitoring Board] and the Ethics Committee independently cleared and reckoned it as a non-related issue to the vaccine trial. Post which we submitted all the reports and data related to the incident to the DCGI [Drug Controller General of India]. It is only after we cleared all the required processes that we continued with the trials.

Questions linger

But public health activists remain unconvinced – and say the clarification has muddied the waters even more. Serum Institute’s statement, they contend, seems to suggest that the trial was paused to assess the adverse event. However, there have been no disclosures at any point to that effect – neither by Serum Institute nor AstraZeneca, or for that matter by India’s drug regulator. “There is no indication that the trial was ever paused or even a brief period of time,” saod Malini Aisola of the AlI India Drug Action Network.

A spokesperson for Serum Institute declined to clarify this. VG Somani, the drug controller general of India, did not respond to calls, messages and emails seeking comment.

Serum Institute’s actions, experts warned, could lead to a trust deficit. “Opacity and false statements lead to mistrust and can damage the prospects of a potentially good vaccine,” said Sandhya Srinivasan, a Mumbai-based public health researcher and journalist.

However, some researchers and scientists have argued that it was not necessary to disclose every adverse event to the public or even the participants of the trial. They needed only to be reported to the institutional ethics committee at the trial site, the data and safety monitoring board and the regulator, said the clinical scientist Gangandep Kang in a television interview.

To disclose or not?

Vasantha Muthuswamy, chairperson of the ethics advisory committee of the Indian Council for Medical Research’s bioethics cell, had a similar take. “Thousands of clinical trials are going on in the world including India and hundreds of SAEs [serious adverse events] are being reported and acted upon to assess the relatedness,” said Muthuswamy. “These are not being publicised as due process is followed by all concerned further course of action to resolve the same or pay compensation wherever it is due.”

Indeed, voluntary disclosures about drug orvaccine trials are rare all over the world. Yet, in the face of public pressure to be more transparent in these extraordinary times where trial timelines have been drastically crunched, more and more companies have shed the old practices of secrecy.

As Srinivasan explained, “Transparency is particularly important when a newly developed vaccine is going to be used on hundreds of millions of people and on the basis of a few months of follow-up.”

Anant Bhan, a researcher in global health, bioethics and health policy, said Serum Institute’s decision to withhold the information was “surprising considering the same company [AstraZeneca] in other cases” has disclosed serious adverse events publicly.

However, some argue that such disclosures could do more harm than good. “In the current sensitive situation making a big issue out of this may give publicity to some, but don’t you think is causing more harm to the society by creating a fear psychosis?” asked Muthuswamy. “Vaccine hesitancy will become more now.”

Vaccine hesitancy refers to the phenomenon of people refusing to get inoculated despite the presence of a safe and effective vaccine.

Bhan did not seem to agree. “Being transparent and upfront is a better idea,” he said. “If people feel the whole process is opaque and some information is being, it could lead to more harm.”

Yet others said that they did not believe Serum Institute’ lack of disclosure was an outcome of heightened vaccine hesitancy in any case. “I can only assume that their reluctance comes from their interest in getting an approved vaccine into the market as soon as possible, getting the government’s contract, and the financial impact of such an announcement,” said Srinivasan.

Regulators role

The Indian Council of Medical Research, which is the co-sponsor of the trials in India, should have also done better, contended Srinivasan. “I imagine it too is under pressure to get a vaccine out as soon as possible,” she said. “The Oxford vaccine seems to meet the standards of efficacy, it’s affordable, and it can be used within India’s immunisation infrastructure. This might explain their reluctance [to be more transparent], but not justify it.”

Amidst all of this, India’s drug regulator, Central Drugs Standard Control Organisation’s muted response has also come under scrutiny. Incidentally it is not the first time in the pandemic that critics have criticised the regulator for a lack of transparency. The controller is responsible for “safety, efficacy and quality” of all medical products manufactured, imported and sold in India. This means it also oversees and sets safety standards for clinical trial of drugs in the country. Yet, there has been no official statement by the drug controller on the matter.

On the evening of December 2, Press Trust of India reported, quoting unidentified sources, that an expert committee set up by the controller had found no connection between the vaccine and the Chennai volunteer’s illness. The person was administered the vaccine on October 1, and hospitalised on October 12 following severe illness; his situation came to light in the last week of November.

“The event happened on October 1, the causality should have happened by early November at the latest,” said Bhan.

Somani, the drug controller general, did not respond to queries seeking an explanation about the alleged delay.

This reporting was supported by a grant from the Thakur Family Foundation. Thakur Family Foundation has not exercised any editorial control over the contents of this article.



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