India’s drug regulator has faced criticism from scientists for its decision to grant emergency use authorisation to Bharat Biotech’s Covid-19 vaccine without phase-three trial data about its efficacy and safety. Now, records of meetings held last week by an expert committee show its members too were apprehensive about the lack of adequate data – as recently as one day before they greenlighted it.

The subject expert committee has been set up by the regulator to examine the suitability of Covid-19 drugs and vaccines. The records show the committee made a sudden U-turn in how it viewed Covaxin, the vaccine developed indigenously by Bharat Biotech. On January 1, it said the vaccine’s “efficacy is yet to be demonstrated”. The next day, it went on to recommend the vaccine for emergency use authorisation.

Clinical trials are divided into three phases. Phase 1 of a clinical trial is usually small and is used to determine its safety profile. Phase 2, on the other hand, employs a bigger sample size, and looks at the immune responses triggered by the vaccine.

However, a vaccine is deemed safe to be commercially available only after Phase 3 – a much larger efficacy trial involving thousands of participants. Covaxin’s third-phase trial is still underway.

On December 30, the company, according to the minutes of the expert committee meeting held that day, “presented updated recruitment status and safety data including SAE [serious adverse event] data of the ongoing Phase III clinical trials”.

The committee, for its part, asked the company to “update and present immunogenicity, safety and efficacy data for further consideration”.

In the next meeting held on January 1, the company submitted data from the “Phase 1 and Phase 2 clinical trial along with the data from the ongoing Phase III clinical trial in the country”.

The committee in the meeting noted that a large trial was underway, but the proposed size of enrolment was yet to be fulfilled. The ongoing trial, the committee noted, “has demonstrated safety till date” but added that “efficacy is yet to be demonstrated”.

The committee then went on to ask the company “to expedite the recruitment and…perform interim efficacy analysis for further consideration of restricted emergency use approval”.

A sudden U-turn

The next day, January 2, the firm presented “updated data, justification and requested for consideration of their proposal in the wake of incidence of new mutated coronavirus infection”. This is seemingly a reference to the new mutation in the virus, first reported in the United Kingdom last month, which makes it more infectious.

This time, the committee’s reluctance seemed to have disappeared. It invoked the “safety and efficacy data from non-human primate challenge study where the vaccine has been found to be safe and effective”.

That, combined with its promising immunogenicity data, was enough for the committee to recommend it “for restricted use in emergency situations in public interest as an abundant precaution, in clinical trial mode, to have more options for vaccinations, especially in case of infection by mutant strains”.

There is curiously no deliberation on its earlier observation – made a day before – that the vaccine’s efficacy was yet to be demonstrated.

The advocacy group All India Drug Action Network said they were “perplexed at the abrupt change in thinking of the SEC [subject expert committee] from the first two meetings to the third day on which the approval was recommended while apparently discounting the need for efficacy data as the condition of the approval”.