In all likelihood, the US drug regulator, the FDA, or other licensing agencies will develop the first emergency approval of a Covid-19 vaccine in conjunction with clinical trials of other ongoing companies. From a certain point of view, the studies could become unethical, the specialists point out, because half of the participants will get a placebo.
“It’s a very troublesome issue,” said Christine Grady, head of the bioethics department at the US National Institute of Health’s Clinical Center, which hosted a webinar on the subject last week.
“It’s important for science to move forward,” says Seth Berkley, who is leading an international project, COVAX, to develop and manage a portfolio of all Covid-19 vaccines. He believes that humanity needs multiple vaccines. Due to costs or side effects, some may benefit a specific group of patients, such as the elderly, pregnant women or patients in low-income countries.
Effectiveness, criterion no. 1
According to the WHO on October 2, 42 vaccines are currently being tested, 10 of which are in phase 3 (last) testing and involve tens of thousands of volunteers, who receive either the vaccine or a placebo, while their health is closely monitored. If its efficacy indices are as planned, manufacturers may request the Emergency Use Authorization (EUA) until the trial is completed. According to the emergency licensing rules issued by the FDA, it is stipulated that a candidate needs an efficiency level of only 50% to prevent cases of symptomatic patients, and as an additional measure of efficiency, to pass 2 months after at least half of the participants received the final dose.
On the other hand, Russia and China have already licensed their own versions of the vaccine, but their effectiveness has not been proven.
The efficacy tests developed by the American program Operation Warp Speed aim to analyze preliminary data from different groups of volunteers (50, 100 or 150 people), who develop symptoms of disease that allow researchers to estimate the impact of the candidate vaccine on people receiving the vaccine, versus those receiving placebo.
Man or society?
Specialists recommend that, in the case of comparative analysis between the vaccines in the samples, priority be given to the individual value over its societal value. In other words, according to Joseph Millum, a Clinical Center employee, clinical research poses ethical challenges because it exposes participants to risks for the benefit of others, not for the benefit of the participants themselves.
But researchers and ethicists cannot easily agree on this dispute. Christine Grady, head of the bioethics department at the Clinical Center at the US National Institute of Health, organizer of the webinar, said that if early vaccine results required emergency approval, participants in the clinical trial would have the right to know if they had received a worthless placebo or a vaccine that could potentially help them. “It’s a benefit that people included in the clinical trial should have access to,” says Grady.
Stanford epidemiologist Steven Goodman agrees that clinical trials for vaccines differ dramatically from other treatment trials, which help sick people. But people who receive a placebo in the test do not need it in the way patients need treatment, he argues.
A widely used vaccine can create herd immunity by slowing the spread of the virus in the community.
A pragmatic motivation
Things get even more complicated when it comes to the impact of an emergency clearance on other Covid-19 clinical trials. If testing for another candidate vaccine needs to start, ethical considerations may require the use of a recently authorized product instead of placebo. If the study is ongoing, especially towards the end, the specialists involved should explain to the participants the value for society in case there will be a continuation of a blind study. This will give them the opportunity to stay in the study, but also to receive the vaccine at the end.
If the approved vaccine provides only a modest benefit, participants will be more willing to continue the study “blindly.” However, a 50% chance of receiving a potentially better vaccine in the end, if they remain in the clinical trial, would be more affordable for volunteers. Many participants have very altruistic reasons for participating in the study, but they must also be offered a more practical motivation, experts say.
The key clue
The key clue to evaluating the effectiveness of the Covid-19 vaccine is antibodies, which will neutralize spikes, the surface protein of SARV-CoV-2, to stop infecting human cells, scientists explain. If trials indicate that a certain level of neutralizing antibodies provides protection against infection or severe form of the disease, this would be a major indicator of comparison between vaccines in tests for the development of the most valid variant. If the spike protein hypothesis proves to be incorrect, it will be the cornerstone of vaccines.
Sursa: Science Mag