What Are the Contentions Over Covaxin’s Efficacy?
At a time when the holy grail of the coronavirus vaccine escapade is turning conclusive, promising and successful, India is also joining its peer nations in terms of launching mass immunisation campaigns across the country in full throttle.
Two coronavirus vaccines (out of the most promising ones on the list) were granted regulatory approvals, effective immediately, albeit on an emergency basis.
There is, however, a critical point that differentiates both these vaccines. While the Oxford-AstraZeneca vaccine (Covishield) received approvals from both India as well as the UK simultaneously after thoroughly reviewed and well-publicised results on a global scale, the indigenously-made Bharat Biotech vaccine (Covaxin) has stirred up extensive and polarising commentary from experts in the medical community and otherwise, owing to the contentious question of its efficacy.
Let’s see about the merits behind these contentions.
What is Wrong With Covaxin?
The Government said that approval for this vaccine has been granted on the “safety and immunogenicity data”, derived from the Phase I and II clinical trials respectively. There is, however, a third precursor to the approval — efficacy data — that is granted after conclusive results are obtained in the Phase III trials.
On November 16th 2020, Bharat Biotech commenced the Phase III trials which enlisted 25,800 participants. The Director of ICMR (which was involved in the development of this vaccine), even stated that so far no safety concerns have been reported from any of the 22,500 participants among the above lot who had received the first shot.
Unfortunately, his testimony isn’t a part of veritable trial data because Phase III trial data for Covaxin still remains unpublished. Which now explains the idea of its employment as a possible “backup” in extremely emergency situations.
Regulatory Trajectory of a Vaccine
In India, clinical trials and approval of new drugs (including vaccines) are governed by the New Drugs and Clinical Trial Rules which were notified in March 2019. A vaccine has to undergo precisely the following stages before receiving regulatory nod for mass production and public use.
Three things you should know:
First, there are different categories of vaccine approvals based on scale and employability of use (e.g. Final use, emergency use, restricted use etc.). The two vaccines approved recently are meant for emergency use, meaning that they can be authorised for use in situations where life-threatening conditions or diseases are imminent.
Second, the term “emergency use” is actually short for “Emergency Use Authorisation” or EUA, which is defined by the US Food and Drug Administration (FDA) as a “mechanism to facilitate the availability and use of medical countermeasures, including vaccines, during public health emergencies, such as the current COVID-19 pandemic”.
Third, there is no identical EUA regulatory equivalent in India. What we have instead is an “accelerated approval process” which allows approvals based largely on the promising nature of clinical trial data, especially if it is meant for a critical cure or treatment, like say a global pandemic.
For now hold on to these points. We will revisit these criteria shortly.
The Problem With Covaxin
The Subject Expert Committee (SEC), on whose recommendations regulatory approval was accorded to the vaccine, mentioned its use for protracted emergency use in “clinical trial mode”.
Now, clinical trial mode means that recipients of the vaccine will have to offer their consent prior to its administration and any possible side-effects emanating therefrom will be monitored.
If you’re a keen observer of paradoxical behaviour, you probably understood by now as to how the twin issues of clinical trial mode and previously-mentioned accelerated approval process are in visible contradiction.
If your doctor determines that your need for a vaccine (that was approved on an accelerated basis) overrides the regulatory requirement of seeking your consent (thanks to clinical trial mode), because it is a life-altering situation, and he administers the vaccine, it will be difficult to determine the implications of the potential side-effects resulting from it later, if any.
Basically, the essentiality trumps the lack of efficiency in a morbid adaptation of Sophie’s Choice!
Extraneous Circumstances
This is the medical analogue for the “national security” metaphor used in political debates. There are, of course, exceptions to ensure that enough care and precaution is taken to obliviate as many possible counterproductive effects of a drug before releasing it to the public. Limit the damages, so to speak.
One, is if the early-stage trial data is definitively positive or way above the precarious threshold. The DGCI is well within its powers to grant approval for a vaccine if it has enough critical mass or promising results at the Phase II trial stage to be marketable immediately.
Covaxin’s Phase II data was based on trials involving 380 participants. Although it indicated accelerated response from immune cells against the virus, the side-effects caused were pain and inflammation in the area of injection.
Two. Probably the biggest variable that has caused such imbalance in the regulatory matrix is the advent of new strains of the coronavirus recently. The new mutant strain that emerged in the UK has now spread to 34 countries already. This is, perhaps, the most unpredicted factor which has influenced the approval of Covaxin as a wild card against the treatment of the newer strains, seeing as the odds of its effectiveness against them can swing widely across the spectrum in both ways, as compared to the vaccines whose Phase III results are already conclusive and definitive.
However, there is no data yet to verify this hypothesis.
As dire as it is to predict the possibilities of a global fight against a deadly virus with the help of a vaccine whose trial results are yet unknown (and hence possibly successful), it is not completely irrational to bank on a Hail Mary pass to fight a pandemic that has already caused wide spread devastation.
(Originally published January 7th 2021 in transfin.in)
