It has been an arduous journey for the first India-developed and manufactured COVID-19 vaccine to get its emergency use authorization approval without added conditionalities. It finally happened at the end of a three-hour long review meeting on Wednesday evening when the 10-member subject expert committee, set up by the Drug Controller General of India finally chose to recommend removal of the clinical trial mode conditionality added to the vaccine under the emergency use authorization (EUA), which it was granted on 3 January 2021.
An expert and a senior official from the government, in the know of the developments, told Financial Express Online that the expert committee “found the interim efficacy data adequate enough to assure safety and efficacy of the vaccine and thereby recommended the removal of the clinical trial mode conditionality.” On why it did not want to wait for the final results, the apparent reason was based on the findings of the study and the current scenario. Clinical trial efficacy, he explained, is based upon how many COVID positive cases are registered post the vaccination and for better efficacy these cases need to be more in the group that is administered the placebo than in the clinical trial arm where the vaccine was injected. In the case of Covaxin, the interim analysis was based on 43 cases out of 130, and of these 43, 36 cases were reported as COVID-19 positive versus 7 cases in the group that was administered the placebo.
The calculation of efficacy is done as 36 minus 7 divided by 36 and multiplied by 100, which in this case comes to 80.6.
One added element, according to the senior official, has also played a role in the decision to recommend the removal of the clinical trial mode with the interim efficacy data. It is apparently to do with the situation in the country where the number of COVID positive cases as a whole are coming down and therefore data on the positive cases post-vaccination will also take a long time leading to inordinate delays despite the vaccine data already providing an assurance on both safety and efficacy. Though, he added that the company will, however, continue its study of all the cases and work on its final results.
Getting to this has not been easy for Covaxin, which was one of the two vaccines to be granted the emergency use authorisation on January 3rd this year. The other vaccine being Covishield, the Oxford-Astra Zeneca vaccine made by Serum Institute of India. However, unlike Covishield, Covaxin was granted the EUA with the added conditionality that the vaccine would have to be administered in a “clinical trial mode.” This meant when administering this vaccine, an informed consent form had to be signed by the recipient of the vaccine and if after the vaccine has been administered and there is any serious adverse health event and later it is proved that it was due to the vaccine then the company would have to pay compensation to the recipient. These conditions were included because back then there was no data available as the phase 3 clinical trials were not completed and therefore the resultant efficacy data was not available.
Now that Bharat Biotech, which developed the vaccine along with the Indian Council for Medical Research (ICMR), has concluded the phase 3 clinical trials and submitted the data about a week earlier for review by the expert committee for removal of the clinical trial mode conditionality, the meeting happened on March 10th. The company had claimed an interim clinical efficacy of 81 percent in its announcement on March 3rd and had got favourable reactions from experts. For instance, one of the well-known experts in this space, Dr Gagandeep Kang had told Financial Express Online: “interim efficacy results are a planned analysis and are showing very good results for Covaxin”. Though, she was awaiting more data granularity. “Now, we have to wait for full results at 130 cases, a breakdown by severity and their secondary outcomes of asymptomatic infection and viral loads.”
The senior official also indicated as things stand the regulatory clearance allowing Bharat Biotech to remove the clinical trial mode conditionality may happen the next two days or so after the changes in the vaccine fact sheet by the company are reviewed.