Indian regulators overlooked 'sloppy science' relating to Covishield: Experts

The simultaneous regulatory approval to the home-grown vaccine without any data on its efficacy has so far attracted a torrent of criticism

Health officials have said the approvals were justified under emergency conditions: Shutterstock

G.S. Mudur   |   TT   |   New Delhi   |   07.01.21 :  Indian regulators overlooked “sloppy science” relating to Covishield, the AstraZeneca-Oxford Covid-19 vaccine, when they approved its restricted emergency use, multiple experts have said.

The simultaneous regulatory approval to the home-grown Indian vaccine, Covaxin from Bharat Biotech, without any data on its efficacy has so far attracted a torrent of criticism.

The experts, however, believe the regulators also made allowances for the AstraZeneca-Oxford vaccine, made in India by the Serum Institute of India.

The Central Drugs Standard Control Organisation (CDSCO), the regulatory authority for drugs and vaccines, on Sunday accepted an expert panel’s recommendations to permit conditional and restricted emergency use of both vaccines.

Health officials have said the approvals were justified under emergency conditions.

“We are in a war-like situation — we need innovative strategies,” Balram Bhargava, director-general of the Indian Council of Medical Research (ICMR), the apex health research agency, told The Telegraph.

India’s Covid-19 epidemic has shrunk from a peak of over a million active patients in mid-September to less than 228,000 on Wednesday. But Covid-19 remains a public health emergency with an average 18,000 new cases recorded daily over the past week. More than 150,000 people have died since the epidemic started.

National drug rules, pencilled in March 2019, allow regulators to approve vaccines on the basis of their capacity to generate immune responses, or immunogenicity, without efficacy data to address “serious or life-threatening disorders”.

“Safety, immunogenicity and efficacy are required in a non-emergency situation,” Bhargava said. “The existing pandemic, the mortality, available science, and lack of definitive treatment were considered (by the regulators) for accelerated approval.”

Bharat Biotech head Krishna Ella, a scientist turned entrepreneur, has accused critics questioning Covaxin’s approval of trying to “throw stones and bash an Indian company” while ignoring issues relating to Covishield.

Two members of India’s national task force on Covid-19 too have said the CDSCO panel’s approval to Covishield reflects a concession to poor science and incomplete data. One task force member has described the approval as an “opaque process”. Both members requested anonymity.

The Serum Institute, while seeking approval for Covishield, had submitted data from AstraZeneca-Oxford’s trial in other countries and safety and immunogenicity data from India. Under Serum’s clinical trial protocol, it was to assess safety in 1,200 volunteers and immunogenicity in 400 volunteers.

However, a senior government researcher told The Telegraph that the company had submitted immunogenicity data on only 185 volunteers, implying incomplete data.

A Serum spokesperson declined to say from how many volunteers the company had submitted the immunogenicity data to the Indian regulators. “But we submitted all data that were required,” the spokesperson told this newspaper.

Paul Offit, professor of paediatrics at the Children’s Hospital of Philadelphia and member of the US Food and Drug Administration’s vaccine advisory panel, is among researchers who believe that the trial data for the current AstraZeneca-Oxford vaccine are not strong enough for a reasonable assessment.

In its interim analysis, AstraZeneca pooled the results of two dosing regimens — one involving two full doses on 8,895 volunteers that showed 62 per cent efficacy, and the second involving a half dose followed by a full dose on 2,741 volunteers that showed 90 per cent efficacy. The pooled data showed 70 per cent efficacy.

“The trial involved two dosing regimens, two time intervals between the two doses, and two placebos,” Offit told this newspaper over the phone. “You shouldn’t combine data, but they did it. It is sloppy science and the data isn’t sufficient for efficacy assessments.”

A member of India’s national task force on Covid-19 expressed surprise at how the CDSCO had assigned an efficacy level of 70 per cent to the AstraZeneca vaccine. “The 70 per cent is a pooled average — when you approve a vaccine for use, you need to specify the expected efficacy for the dose approved.”

With existing data, Offit said, the AstraZeneca-Oxford vaccine would not get US FDA approval.

“The strategy of using an adenovirus to generate immune responses against the novel coronavirus may be perfectly viable, but needs to be convincingly demonstrated,” Offit said. The vaccine would need to be shown as effective through larger trials.

The efficacy trials of the Pfizer-BioNTech and Moderna vaccines — both approved for emergency use authorisation by the US FDA in December — had involved over 30,000 and 43,000 volunteers.

The home-grown Covaxin’s efficacy trial in India has recruited around 24,000 volunteers and, scientists say, the efficacy results can be expected only after March this year. The vaccine was approved only on the basis of its safety and its capacity to generate a robust immune response.

“Ultimately, Covaxin’s data from India will be much larger and stronger than Covishield’s,” Gagandeep Kang, professor of microbiology and a vaccine expert at the Christian Medical College, Vellore, said. “But at the moment, the data package for Covishield includes efficacy; Covaxin’s does not.”

Kang, however, said that while the AstraZeneca trial data from the UK are “messy”, they show efficacy.

The national task force member said the CDSCO panel’s approval process remained “opaque”. What data the panel had reviewed and what was discussed remains unknown — the minutes uploaded show only the outcomes.

For instance, it is unclear what made the expert panel change its stance on Covaxin within 24 hours. In a January 1 meeting, the panel had asked Bharat Biotech to provide “interim efficacy analysis” for consideration for emergency use.

The interim efficacy analysis is likely possible several weeks away. But on January 2, the panel granted emergency use approval, raising a question from critics — what extra input had the panel received over the course of a single day to change its stance.

“For the sake of transparency, the drugs controller-general of India (the head of the CDSCO) should respond to the questions being asked,” said Shahid Jameel, a senior virologist and director of the Trivedi School of Biosciences, Ashoka University, Sonipat (Haryana). “The DCGI and CDSCO are silent. This (silence) has muddied waters, not people raising questions.”

The UK, Argentina and India have approved the AstraZeneca-Oxford vaccine, widely described as the “vaccine for the world” because of its low cost and the relative ease of transporting it compared with the Pfizer and Moderna vaccines.

Covishield, developed by researchers at the University of Oxford, uses a chimpanzee adenovirus containing the genetic sequence of SARS-CoV-2, the virus that causes Covid-19.

Covaxin contains an inactivated (killed) strain of SARS-CoV-2 isolated by researchers at the National Institute of Virology, Pune. The Hyderabad-based Bharat Biotech developed the strain into a vaccine and is conducting clinical trials.