Bharat Biotech got an approval for its COVID-19 vaccine and along with it came a lot of flak from critics who believe that the process was rushed for no valid reason. Dr Krishna Ella, the founder and chairman of Bharat Biotech, retaliated blaming everyone from the media to rival vaccine makers, except that his arguments hold no water. The drug regulator's approval for any new drug or vaccine is based on the understanding that the drug or vaccine's benefits outweigh its risks. However, considering that he admitted that Phase-III trials are still underway, there is no final estimate of Covaxin’s efficacy, and without that number, the approval should not have been granted. Benefits like how effective the vaccine is in preventing disease, and risks such as high mortality rate if the vaccine is not given or vaccine side-effects, are critical data that inform the approval. This benefit-to-risk ratio changes based on the vaccine and disease being considered, but there is no escaping the need for this data. It is, therefore, strange that the vaccine candidate being explored by Bharat Biotech-ICMR, Covaxin, has<a href="https://pib.gov.in/PressReleaseIframePage.aspx?PRID=1685678"> received</a> permission "for restricted use in emergency situation in public interest as an abundant precaution, in clinical trial mode, specially in the context of infection by mutant strains." Bharat Biotech has<a href="https://www.medrxiv.org/content/10.1101/2020.12.11.20210419v1"> shared</a> findings from their Phase I/II clinical trials as a pre-print on MedRxiv. These studies indicate safety and immunogenicity (i.e., the vaccine candidate's ability to generate an immune response) in human beings. However, Bharat Biotech<a href="https://www.livemint.com/science/health/bharat-biotech-begins-phase-3-trials-of-covid-19-vaccine-covaxin-in-india-11605570981150.html"> began</a> Phase III trials demonstrating the vaccine's efficacy instead of a placebo only on November 16. By December 22 they had<a href="https://www.business-standard.com/article/current-affairs/bharat-biotech-recruits-13-000-volunteers-for-covaxin-phase-3-trials-120122200562_1.html"> recruited</a> only 13,000 volunteers of the target 25,800 participants. The endpoints for the data collection on efficacy are Day 42 to Month 12, as per information<a href="http://ctri.nic.in/Clinicaltrials/showallp.php?mid1=48057&amp;EncHid=&amp;userName=CTRI/2020/11/028976"> submitted</a> to CTRI. It is therefore unlikely that any robust data about the effectiveness of the vaccine is available. Reports<a href="https://theprint.in/health/bharat-biotechs-covaxin-given-conditional-nod-based-on-incomplete-phase-3-trial-results-data/578389/"> suggest</a> that approval was based on immunogenicity data for 10,000 people after they have received the first dose of the vaccine and for 10,000 people after two doses. However, none of this data is available in the public domain, nor has it been peer-reviewed by independent experts. The Subject Expert Committee (SEC) made the recommendation of approval – however, very little is known about the composition of the Committee or the process followed for this approval. It will be premature to determine that Covaxin's benefits outweigh the risks without data on its efficacy. The opaqueness of the approval process adds to the scepticism that is forming around this vaccine. On the other hand, the US Food and Drug Administration has been very transparent with their evaluation of approved vaccines. Its<a href="https://www.fda.gov/news-events/press-announcements/fda-takes-key-action-fight-against-covid-19-issuing-emergency-use-authorization-first-covid-19"> announcement</a> for the Pfizer vaccine, for example, gave details on how many people had received the vaccine and placebo, the effectiveness of the vaccine, and, most importantly, the limitations of the vaccine. It provided a plan for vaccine monitoring and demarcated the company's responsibilities in the future. The discussions of the advisory panel that recommended approval of the vaccines were also<a href="https://www.statnews.com/2020/12/17/moderna-vaccine-fda-panel/"> made</a> public. Both Emergency Use Authorizations (EUA) were given based on Phase III data. In addition, both Moderna and Pfizer have published their trial data in peer-reviewed journals. China and Russia - which approved vaccines with insufficient Phase III data – have<a href="https://www.businesstoday.in/sectors/pharma/covid-19-crisis-scientists-flag-concerns-over-vaccines-from-russia-china/story/414747.html"> attracted</a> scepticism over this process. The constraints placed on the Indian economy and health crisis created by COVID-19 demand expedited approval processes; however, lack of efficacy data cannot be substituted in this fast-tracking process. So what more information do we need? Bharat Biotech and ICMR need to demonstrate the efficacy of the vaccine through published data. Phase III trials can take time, but it will be the correct and ethical way to get the vaccine approval. The government needs to be transparent on how approvals were given and what data were presented. Also, in future, government laws need to be clear on minimum standards that drugs/vaccines need to adhere to for approval. For example, FDA had mandated a minimum efficacy of 50% as a prerequisite for the EUA. It is therefore questionable how Covaxin was approved if Indian authorities followed a similar benchmark. A pandemic requires expedited decision-making, but moving the goalposts for different vaccines is not advisable. The government also needs to clarify the terminology used in their approval, primarily, the terms "restricted", "abundant precaution", and "clinical trial mode". A clinical trial requires constant follow up with participants, a special consent form explaining the risks of the vaccine, and a placebo group. It is unclear how those deemed eligible for Covaxin will be divided into these two groups or how the data will be collected and analysed. It is also unclear who will be responsible for this monitoring. The claim that the Bharat Biotech vaccine is more likely to be effective against mutant coronavirus strains is theoretical and needs to be backed by data. In this case, Bharat Biotech first needs to show efficacy against the original strain as well. In the absence of this data, investment in the vaccine may lead to no positive public health outcomes in India. It may be better to wait for the Phase III interim data and make an informed decision on including it for emergency use. The demand for vaccine efficacy data is not an attack on Bharat Biotech or its vaccine, it is simple scientific requirement that needs to be fulfilled. The impact of this opacity in regulation should go beyond Covaxin and Bharat Biotech. India is the largest vaccine manufacturer in the world. But we are behind in the technology and expertise in creating vaccines. For India to be a world leader in public health, we need to be ahead on indigenous vaccine research and manufacture. However, the scepticism generated by the ambiguity and double standards of the current approval process reduces confidence and credibility in locally made vaccines. The author, Shambhavi Naik, has a PhD in Cancer Biology and is a Fellow at Takshashila Institution, Bengaluru. SEE ALSO: <a href="https://www.businessinsider.in/india/news/bharat-biotech-sees-rivals-conspiracy-in-all-the-criticism-for-the-approval-for-covaxin/articleshow/80099818.cms">Bharat Biotech sees rivals’ conspiracy in all the criticism for the approval for Covaxin</a> <meta content="cms.next" name="cmsei" />

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