Pune’s Serum Institute of India and Hyderabad-based Bharat Biotech received the Drug Controller General of India’s approval on January 3 for “restricted” use of their Covid-19 vaccines in an “emergency” situation.
With less than a week left before India starts its nationwide inoculation drive, batches of coronavirus vaccine are being shipped to multiple parts across the country. As many as 3 crore healthcare and frontline workers will be the first in line to receive the shot. Pune’s Serum Institute of India and Hyderabad-based Bharat Biotech received the Drug Controller General of India’s approval on January 3 for “restricted” use of their Covid-19 vaccines in an “emergency” situation.
After Serum Institute’s maiden consignment of Covishield vaccines took off for Delhi from Pune on Tuesday, Bharat Biotech also dispatched the first batches of Covaxin, its two-dose Covid-19 vaccine, to 11 cities across India. The Hyderabad firm said it had successfully shipped the first batch of the vaccines to Ganavaram, Guwahati, Patna, Delhi, Kurukshetra, Bangalore, Pune, Bhubaneswar, Jaipur, Chennai, and Lucknow.
As of Tuesday, 54.72 lakh doses of the two vaccines cleared for use by the national regulator had reached vaccine stores across the country, the government said. With limited doses of Covid-19 vaccines available initially, the Centre said states will not have the option to choose which vaccine to administer to its priority groups.
Challenges in recruiting
In a webinar hosted by DBT on December 31, Krishna Mohan, Executive Director of Bharat Biotech, had mentioned about the challenges in recruiting participants for phase-3 trial, as many felt they had only a 50% chance of getting the candidate vaccine. The news about vaccines soon becoming available made the recruitment even more challenging.
Pankaj Patel, Chairman of Zydus Cadilla said during the webinar that he anticipates difficulties in quick recruitment of volunteers but not with recruitment per se. “There are enough people committed to helping clinical studies. It might take longer but there won’t be a challenge with recruitment,” he said.
Effects of approval
Now, with two vaccines approved for restricted use, how much more challenging will it be to enrol participants for clinical trials, particularly phase-3 trials that need 25,000–30,000 people? it would be more challenging than earlier for this reason,” says a medical expert.It would be challenging to recruit participants now. With the daily cases coming down, many people who would have volunteered would not see the urgency now as earlier. Also, with increasing numbers of infected people, there would be a reduced pool of susceptible people. Prior infection is an exclusion criterion.
Issues with slow spread
With the number of daily fresh cases slowing down since mid-September despite the winter and festival season, the spread of the virus appears to be slowing down. This raises an altogether different challenge in carrying out phase-3 trials where the efficacy of the vaccine is measured by comparing the number of COVID-19 cases and the kind of protection offered in participants in the vaccine arm vis-à-vis the placebo arm. China had to rely on other countries to carry out phase-3 trials of its vaccines as the virus spread had slowed sharply.
As per medical experts it is going to be a challenge, mostly because of the requirement of certain cases to develop in the trial after vaccine administration to understand efficacy.It is best to recruit participants based on an antibody test, and have two distinct groups of people to participate (both infected and susceptible) in trials to understand the efficacy in both groups. This will ensure reaching the sample size efficiently. Professor of Microbiology at CMC Vellore, Dr. Gagandeep Kang says vaccine manufacturers can carry out phase-3 trials outside India and efficacy results from such trials would be accepted by the Indian regulator for vaccine approval.
Health-care workers are relatively better informed of clinical trials and are more likely to participate in trials. However, with the government vaccinating them on priority, this section of potential participants will now hesitate to take part in COVID-19 trials. Some medical experts see another reason why health-care workers would hesitate to participate in trials when they have been prioritised to get the vaccine. Why would health-care workers participate if they are at high risk of infection, in line of vaccination, but have only a 50% chance of getting a vaccine?”
Testing younger people
Older people are particularly at risk of developing severe disease, and even dying, compared with younger people. That is precisely the reason why people over 50 years are one of the four high-risk groups to get the vaccine on priority. Since vaccines would become available in the market only after the government finishes vaccinating the priority groups, which would take many months, will trials be able to recruit only younger people?
Less than ideal
Only in an ideal situation will 100% of older people get vaccinated on priority. There will always be a certain percentage of older people who might be missed. Enrolling such people then depends on individual trial sites, says experts.
Younger people can be induced to participate in phase-3 trials. But the vaccine will then only be tested largely in a young and generally healthy group, unlike the population it would target when approved.
Serum Institute suing a Covishield trial participant for ₹100 crore has surely not helped in encouraging people to participate in trials.That was a public-relations disaster. The picture that emerged was a company abandoning and threatening a trial participant who volunteered initially for no monetary gain. Medical experts say the behaviour of the company was akin to intimidating the participant. It would have been ideal for the manufacturer