A potential COVID-19 vaccine ought to confer at least 50% protection and be able to either prevent infection or disease — but not necessarily both — according to draft guidelines issued by the Central Drugs and Standards Control Organisation, the apex regulator of drug and vaccine trials.
These guidelines are similar to standards set by the World Health Organization (WHO) as well as peer international regulatory organisations such as the United States Food and Drug Administration (USFDA).
Early tests on monkeys of the AstraZeneca-Oxford University candidate vaccine had shown that while some animals that got the vaccine contracted infection, they did not contract a lung infection or other severe manifestations of the disease. The same vaccine candidate is now being tested in Phase 3 clinical trials in several countries, including by the Pune-based Serum Institute in India.
The Hyderabad-based Bharat Biotech Limited, which is also developing a vaccine candidate, Covaxin, based on an inactivated virus, reported that its tests on animals showed no presence of the virus. In animal trials, all animals are deliberately infected with the SARS-CoV-2 virus and the responses of the vaccinated and unvaccinated group are compared. Because such deliberate infections are not allowed in people, trial designers deploy statistical techniques to decide on whether the administration of the vaccine has a protective effect.
“To ensure that a widely deployed COVID-19 vaccine is effective, the primary efficacy endpoint point estimate for a placebo-controlled efficacy trial should be at least 50%,” the guidelines released late on Monday note. They also specify a probability range that results must be confined to, and it’s these statistical boundaries that determine how many volunteers must be recruited to get reliable estimates of the vaccine’s efficacy.
“All vaccines for respiratory viruses are not always 100% effective,” said Dr. Balram Bhargava, Director General, Indian Council of Medical Research (ICMR), at a press conference on Tuesday, “The WHO says for a vaccine that safety, immunogenicity and efficacy are the three criteria. We are aiming for 100% efficacy but that’s unlikely being a respiratory infection, and so the target is 50% and above.”
AstraZeneca in its publicly released trial protocol last week said that there would have to be 150 people ill with confirmed coronavirus among participants who were vaccinated or received placebo shots to determine whether the vaccine was good enough. As per the USFDA guidelines, it would also evaluate the number of those ill and those not in vaccinated and placebo groups when there were 75 confirmed cases, and this could be a basis for early completion of trials.
U.S. biotech firms Moderna and Pfizer have also released such trial protocol though such details have not yet been given by Indian companies.
Before companies embark on trials in India, they have to disclose on a public website, managed by the ICMR, what the primary and secondary outcomes of the trial are. In the case of COVID-19 , companies have a choice of determining whether the presence of virus or manifestation of disease would be a primary outcome or not. This is apart from details on the occurrence of adverse reactions, severe unexpected reactions, and tolerance to the vaccine.