Sadly, the government’s piecemeal statements on the conditional clearance are only adding to the confusion
In the case of Moderna’s US approval, more than 30,000 persons were enrolled in the Phase 3 trials and 196 of them got Covid-19 afterward (Representative image; AP photo)
Now that the government is almost ready to start its vaccination drive, it is important it clear the air on the controversy over the clearance given to the Bharat Biotech vaccine. Since it is still not clear what exactly the ‘in clinical trial mode’ clearance entails – it cannot be a clinical trial as there is no control group – it would be a good idea to guarantee that everyone being vaccinated will be given the Serum Institute (Oxford-AstraZeneca) Covishield shot and, if Bharat Biotech’s Covaxin is offered, potential recipients be allowed to reject it and instead get Covishield. The Subject Expert Committee believes Covaxin has the potential to tackle various new strains of Covid-19; to quote health minister Harsh Vardhan, “it contains immunogens (epitopes) from other genes in addition to those from spike protein”. But this is a theoretical possibility, it needs to be proven in the Phase 3 trials; nor is it clear that Covishield will not be able to tackle the mutations.
If it wasn’t bad enough that no questions were entertained at the press conference where the clearances were announced, ICMR chief Balram Bhargava’s comments have only added to the confusion. Justifying the clearance, he said on Tuesday, the immunogenicity and safety of Covaxin had been demonstrated from the Phase 2 trials, and that this is a surrogate for efficacy. If the relationship were as straightforward, why even ask for Phase 3 human trials since that can delay the approval process by several months as volunteers have to be enrolled, given the shots over a period of a few weeks and then observed for at least two months for the initial results?
Not surprisingly, while Cadila Healthcare presented safety and immunogenicity data from its Phase 1 and 2 trials, SEC gave it permission to start Phase 3 trial for its DNA vaccine and said the efficacy of the vaccine ‘should be assessed on the data generated after day 84 from the first dose’. Long observation periods are in line with the global practice and while many continue to believe that several vaccines have got clearances abroad without Phase 3 trials being completed, this certainly does not apply to vaccines like Pfizer, Moderna and Oxford-AstraZeneca. In the case of Pfizer’s UK approval, for instance, data for over 36,000 participants in Phase 3 trials was examined; while 170 of these persons contracted Covid-19 in the post-vaccine trial period, 162 were those that got a placebo and 8 got the vaccination, giving an efficacy of around 94%. In the case of Moderna’s US approval, more than 30,000 persons were enrolled in the Phase 3 trials and 196 of them got Covid-19 afterwards; 185 from the placebo group and 11 from the vaccine group. Indeed, when people talk of small samples of around 200 being used to grant clearances, they mistakenly assume the Phase 3 trial comprises only those who get Covid-19.
In addition to this, the government also needs to take a call on what kind of immunity from lawsuits is to be given to vaccine-makers; such immunity has been given by several countries and will play a critical role in not just the price, but also the availability of vaccines. And though the Covishield permission is for two shots with a 4-6 week gap between them, the UK has moved to a 12-week gap for Oxford-AstraZeneca as this increases the efficiency of the vaccine – the initial belief was this was the result of a half-dose followed by a full-dose – to around 90%; since India’s regulators have followed the UK regulators on the Oxford-AstraZeneca clearance, they will need to take a call on this as well. Other options are also being worked on, including an Oxford-AstraZeneca tie-up with Russia’s Sputnik – one dose of the first followed by another of the second – but that will be considered only after detailed trials.