The Central Drugs Standard Control Organisation (CDSCO), India’s top drug regulator, will only approve Covid-19 vaccines that meet parameters, such as their ability to show they can improve clinical outcomes by at least 50 per cent during human testing. This means that Covid vaccines approved in India must be able to reduce the frequency of those inoculated being clinically diagnosed with the disease by 50 per cent or higher, according to experts.
The regulator, which released a new set of guidelines for Covid-19 vaccines on Monday, also emphasized that the statistical range of efficacy (the ability to produce the desired outcome) in the human trials cannot be lower than 30 per cent.
The guidelines come several months after the World Health Organization (WHO) and the US Food and Drug Administration (US FDA) released their own guidelines for Covid-19 vaccine approvals and draw from both documents, according to experts that have been closely tracking and involved in Covid-19 vaccine developments.
“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 percent, and the statistical success criterion should be that the lower bound of the appropriately alpha-adjusted confidence interval around the primary efficacy endpoint point estimate is (greater than) 30 percent,” stated CDSCO.
“What this essentially translates to is that the trial size has to be sufficient so that if the investigators get exactly 50 percent efficacy, we should have confidence that it will not be less than 30 percent,” said vaccine scientist and Christian Medical College, Vellore professor Dr Gagandeep Kang.
What this means?
The regulator is trying to ensure the candidate approved for mass vaccination shows an improvement of at least 50 per cent over the status quo. This means the number of people who develop symptoms, and are diagnosed by a doctor with Covid, should reduce by at least 50 per cent upon vaccination, as opposed to those who aren’t vaccinated.
“In a clinical trial, they are recruiting a certain number of patients to represent a larger population. CDSCO is saying that the basis of the primary objective should be to show an improvement in clinical symptoms,” said Dr Davinder Gill, former CEO of Hilleman Laboratories. “Considering the efficacy parameter, this means that the number of vaccinated participants that have been diagnosed by a doctor to have Covid-19 after vaccination should be at least 50 percent less than those in the placebo group. This number cannot be less than 30 percent,” he said.
According to him, objectives like “carriage” of the virus, or the reduction of transmission of the virus itself, cannot be the sole reason for receiving a licence from CDSCO to market the vaccine in the country.
“SARS-CoV-2 infection (whether or not symptomatic) should be evaluated as a secondary or exploratory endpoint, if not evaluated as a primary endpoint,” stated the draft.
“Essentially, if the primary endpoint is virologically confirmed disease–which means you must be sick and test positive for the virus to count as a case–as a secondary endpoint, you could test positive but may not be sick,” said Dr Kang.
“The guidelines are an amalgamation of WHO and US FDA guidance and are good to have. It would have been good to have a table stating what is essential and what is optional, particularly for safety monitoring, as safety concerns are affected by the vaccine platform,” she added.
The “first” goal for a Covid-19 vaccine in India would be the “reduction of mortality” in the vulnerable population, Dr VK Paul, Member (Health), Niti Aayog, who chairs the National Expert Group on Vaccine Administration for Covid-19.
CDSCO has also clarified in the draft that persons infected with the SARS-CoV-2 virus in the past should be included in vaccine testing, as long as they do not have “acute” Covid-19 or other acute infectious illnesses.
“Vaccine safety and COVID-19 outcomes in individuals with prior SARS-CoV-2 infection, which might have been asymptomatic, is also important to examine because pre-vaccination screening for prior infection may not be feasible in practice when the COVID-19 vaccine is approved and introduced in the market,” stated the 40-page draft.
“Therefore, subjects with history or laboratory evidence of prior COVID-19 infection should not be excluded from COVID-19 vaccine trial,” it added.
The guidelines are aimed at offering more clarity to vaccine firms that have been in the dark about India’s requirements where Covid-19 vaccines are concerned.
In early August, three vaccine firms raised the ambiguity in guidelines for Covid-19 vaccines, including their level of efficacy, during a panel discussion in Hyderabad.
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