Israelis participating in clinical trials of a locally produced potential vaccine against the coronavirus can still get the vaccine made by Pfizer, health authorities clarified on Sunday.
Clinical trials of any drug or vaccine involve controls: one group receives the actual active ingredient and another group gets a placebo, which has no biological effect. Under normal conditions, neither the tester nor the testee know in advance whether a subject received a real drug or placebo.
Now however due to the circumstances, if a test subject wishes to receive the Pfizer inoculation, their file will be opened; if they received a placebo and not the Israeli vaccine, they will be informed accordingly. Placebo recipients can then get the Pfizer shot, explains Dr. Erez Birnbaum, CEO of the Assuta Ashdod Medical Center, which is one of the sites at which the Israeli vaccine is being tested.
“The trial procedure won’t affect the opportunity and the ability of any patient to receive the Pfizer vaccine if and when it is wanted,” Birnbaum spelled out.
Put otherwise, the subjects don’t have to remain in the trial to the end, which could lead to the elimination of the trial control group.
The Israel Institute for Biological Research in Nes Tziona, which is developing the vaccine, had notified trial participants in advance that if they wish, at any time after joining the Israeli vaccine study, to receive the Pfizer or Moderna coronavirus vaccine, it would reveal if they received a placebo or a genuine Israeli vaccine.
Dozens of coronavirus vaccines are under various stages of development around the world. All face the same issue – a safe and effective vaccine has been developed, potentially obviating the need for theirs; and requiring thought as to how to handle the control groups in clinical trials of these other vaccines, in practice and ethically.
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“The dilemma is whether to breach the framework of the study,” says Dr. Yasmin Maor, the head of the Infectious Disease Unit at the Wolfson Medical Center in Tel Aviv. “The problem arose during discussions at the U.S. Food and Drug Administration last week regarding the Pfizer vaccine and what to do with those who received a placebo, and how to conduct additional studies. No conclusions were reached, but clearly, the moment that the double blind trial is cancelled and the subjects learn to which group they belong, and the vaccine is administered to those who received a placebo – that undermines the information being collected by the study.”
This is quite the conundrum: what should prevail – the rights of the subjects or the scientific greater good.
What options are open to the decision makers?
“There are three models. One option is to do nothing. The placebo will continue to be a placebo, and we’ll continue to keep track of them,” Maor says.
TheMarker countered that anybody can now test for antibodies and find out.
“True. Anyone who really wants to know, can know. But beyond that, there’s also an ethical problem here. A second option is to open the files, identify the placebo group, and enable them to be vaccinated and still continue to keep track of them.”
But if they received a vaccination, they’re no longer a placebo group.
“True, but it could still be a different group, because they received a vaccination later. There will be more limited learning here, but it won’t be zero learning.”
And what’s the third option?
“A gradated option: to open the files and discover who’s in the placebo group, but not to offer the vaccine to all of them at once as a priority, but to have people in the placebo group also receive the vaccine based on the actual prioritization of the country where they live. In that way their right to be vaccinated won’t be affected. On the other hand they won’t receive priority, and that will give more time for a follow-up.”
Weighty ethical questions are coming up here.
“True. First, it’s unfair to withhold a vaccine the moment that it’s clearly effective. Another weighty ethical problem is anticipating the future: If people know that the fact that they took a risk and volunteered for a study affects them negatively, and delays receipt of a vaccination that others can receive then in future, with other diseases and other studies, it will be difficult to find volunteers. We must take that into account in the overall view of the medical world.”
Will dozens of pharmaceutical companies now researching a coronavirus vaccine be able to continue with their studies?
“Yes, but the studies will be different. It will be possible, for example, to compare the vaccine with another vaccine that has already been approved. The question won’t be just whether the new vaccine is safe and effective, but which vaccine is preferable, and in what way.”
Perhaps the control group can simple be composed of people who don’t want to be vaccinated?
“In principle that’s possible, but there are problems here. The problem is that it changes from a controlled double blind study, in which no participant knows whether he received the vaccine or the placebo, to an open study in which people know which group they’re in. These are things that have an effect and create certain biases, for example on reports of side effects. It’s important to conduct such studies, but you have to be aware of their limitations.”