The decision to halt the global clinical trials of a coronavirus vaccine being developed by Oxford University and AstraZeneca, after a serious side-effect was reported in a participant, might be a setback in the quest to get an early vaccine, but it could very well be a blessing in disguise.
It is likely to temper the public expectation and excitement about a vaccine being available very soon, ward off political pressure to rush through the development process and make it ready by a particular date, and force all the developers to scrupulously follow the process, even as they try to fast-track the development.
“This is nothing to be alarmed about as of now. These things happen quite routinely during vaccine or drug trials. The good thing is that despite the rush to produce a coronavirus vaccine, we still have systems in place that would pick these things out. So that is reassuring,” said Shahid Jameel, a virologist.
“When such things emerge, you have to pause, reassess, re-examine. And that is what seems to be happening in this case. This is normal process, and this is how it should be,” he said.
The Oxford University/AstraZeneca candidate vaccine is undergoing phase-3 clinical trials at more than 60 locations in the United States, and also in Brazil and South Africa. It is the same vaccine that was cleared for combined phase-2 and phase-3 trials in India. Those trials also began last month, and would be affected because of this decision.
This vaccine has for long been considered to be one of the most promising ones that are being developed. More than a billion doses of this vaccine has already been pre-booked by countries, even as the human trials were continuing.
In a statement, AstraZeneca has described the decision to halt the trials as “routine action which has to happen whenever there is potentially unexplained illness in one of the trials”. It is being described as a precautionary step. Side-effects are not unexpected in the participants, but this one is reported to be not just serious but also unexplained as of now.
While there is no question mark over the safety of the vaccine as yet, this incident does highlight the uncertainties inherent in vaccine development, and the importance of scrupulously following all the steps in the clinical trials.
In the current haste to produce a coronavirus vaccine, considering the prevailing emergency health situation, several usual regulatory procedures have been bypassed, raising concerns among many scientists and experts. A coronavirus vaccine was earlier expected to be ready by early next year. That itself would have made it the fastest developed vaccine ever. But now there is an attempt, especially in the United States, to release the vaccine this year itself. There is also a political push to get the vaccine released before the November 3 Presidential election. President Donald Trump, who is seeking a re-election, has repeatedly said that a vaccine could be available this year, possibly before the November 3 deadline as well. The availability of the vaccine is seen as boosting his re-election chances.
But elsewhere as well, there has been a rush to come out with a coronavirus vaccine, even if that meant skipping phase-3 clinical trials altogether. That is what has happened in the case of Russian vaccine, and a couple of candidates in China. These vaccines have been approved in their countries, without the phase-3 trials having been initiated. It is only now, after much criticism, that these vaccines are also preparing to undergo phase-3 trials.
In the phase-1 of clinical trials, usually carried out on a small group of people, just about one or two dozen, researchers check whether the vaccine candidate is safe or not, meaning whether or not it induces any harmful side effects in the human body. The phase-2 trials, usually carried out on a few hundred participants, is mostly about checking whether the vaccine triggers adequate immune response in the body.
The phase-3 trials are the most comprehensive and time-taking. It is usually carried out among several thousand participants. The leading contenders for the coronavirus vaccine are trying to enrol between 20,000 to 60,000 participants for phase-3 trials. The AstraZeneca vaccine intended to enrol 30,000 volunteers. This last stage of trials is all about checking the effectiveness of the vaccine in real-life situations, not in laboratory condition. Participants in this stage are allowed to go about their normal life. Some of the participants are given a placebo, or a dummy vaccine, and these form the control group, while the others get the real thing. No one knows what they have got. And after some time, all of them are assessed to see whether they have been able to ward off the infection. If those who have been give the real vaccine show a higher resistance to the disease than the control group, the vaccine is considered to be effective.
In the current case, regulators like the US Food and Drug Administration has said it would approve a vaccine if data showed it was at least 50 per cent effective.
Unlike phase-1 and phase-2 trials, where the volunteers are chosen to be healthy adults, phase-3 trials involve a very large number of participants some of whom can have underlying diseases or weaknesses. As a result, it is not unusual for a case like the current one to emerge during the trials.
Also, in phase-3 trials participants are usually followed up for several months, sometimes years, to see how they are responding. Such extended follow-ups are necessary also to assess how long the effectiveness of the vaccine stays.