It is the only way to get the vaccines on the market quickly.
Dozens of scientists – including fifteen Nobel Prize laureates – write this in an open letter addressed to Dr. Francis Collins, the director of the US National Institutes of Health . In the letter, the researchers passionately argue for so-called ‘ human challenge trials ‘ that can give an enormous boost to the development of a safe and effective vaccine against SARS-CoV-2.
Human challenge trials
Traditionally, developing a vaccine has taken quite some time. And also testing it is a time-consuming opportunity: all vaccines have to go through different phases before being eligible for approval. Of great importance are the three phases of clinical research, in which the vaccine is administered to increasingly large groups of people to test its effectiveness and safety. In the first two phases of this clinical trial, effectiveness is assessed by looking, for example, at the antibodies people produce after they receive the vaccine. But in the third phase it must become clear whether the vaccine can actually prevent people – if they come into contact with the pathogen against which the vaccine must protect – from becoming ill. At this stage of the study, a large group of people – often tens of thousands of test subjects – will be divided in two, after which one group will receive the vaccine and the other a placebo. These people are then sent home. And over time it must become clear whether infections by the pathogen against which the vaccine protects must actually be less prevalent among the group that has been vaccinated.
It is a robust experiment. But you can imagine that the experiment takes a lot of time. After all, you should actually wait for test subjects to come into contact with the pathogen. And for the sake of goodness, quite a few of the subjects need to be exposed to the pathogen if you want to demonstrate convincingly that there is a significant difference between the frequency of the disease among the vaccine-vaccinated and the placebo-vaccinated groups.
However, there is a way to speed it all up. Namely by proceeding to human challenge trials in this third phase of clinical research . Here too, some of the subjects receive the vaccine and another part a placebo. However, instead of waiting for exposure to the pathogen, the subjects are deliberately exposed to the pathogen under controlled conditions some time after administration of the vaccine.
It sounds like a radical idea, but the signatories to the open letter see it quite differently in the fight against COVID-19. “A safe and effective vaccine will be incredibly valuable and the sooner it is, the better,” said Alvin Roth, of Stanford University and one of the Nobel laureates who wrote their names under the open letter. “ Challenge trials make sense. We have to prepare them carefully and then go on bravely. ”Previous human challenge trials
Human challenge trials are nothing new. They have been used more often in the past to study pathogens and as such have also contributed to the development of various vaccines. For example, in 1796 Edward Jenner administered the smallpox vaccine he developed to his eight-year-old son, and subsequently exposed it to smallpox. The boy did not get sick. Jenner then repeated the experiment with another 6,000 subjects. The vaccine proved itself and ultimately led to the disease being eradicated 200 years later. Vaccines against cholera and typhus have also been developed thanks to similar experiments. The human challenge trials have not always been ethical in the past. For example, today no one would think of vaccinating an eight-year-old child and exposing it to a life-threatening illness. The scientific and ethical standard is now much higher and many see the human challenge trials as acceptable, as long as specific guidelines are met.
As Roth points out, safety must also be paramount in these experiments. That is why the researchers also state in their open letter a number of guidelines for the human challenge trials . For example, subjects should be relatively young and in good health. “The chance of people between 20 and 29 years old succumbing to the coronavirus is comparable to the mortality risk of living kidney donors,” the open letter read. Kidney donation is a fairly common procedure that can be roughly compared to the human challenge trials, the letter reports, because this procedure is also justified by the consent of the donor and the help of others. In addition, it is very important that all subjects who participate in the experiment are closely monitored and can count on the best possible care. In addition, experiments must be monitored both scientifically and ethically. Finally, it is very important that the test subjects participate voluntarily and also know what they are getting into. “If done right, human challenge trials could be an important way to accelerate vaccine development and ideally save the lives of millions worldwide,” the researchers concluded in their letter.
You may wonder if there are people who are willing to take this risk from the goodness of their hearts. The researchers have no doubt about that. “Decades of psychological research into altruistic behavior have shown that a large – and probably growing – part of the general population purely from altruism and not because they are insensitive to risks (…) are willing to take risks to help others. ” This conclusion seems to be supported by the fact that more than 31,000 people from 140 countries have already registered via the website 1daysooner.org for possible human challenge trials in which they will be deliberately exposed to the corona virus.”WE BELIEVE THAT HUMAN CHALLENGE STUDIES WOULD BE FEASIBLE AND INFORMATIVE IN THE COMING MONTHS”
And researchers therefore see no reason to have the healthy, young and well-informed people among these volunteers participate in a human challenge trial. In fact, in a sense they see it as a duty to set up these experiments. Because the sooner there is a vaccine, the fewer people who become infected with the virus and the more lives can be saved. In short: the end justifies the means. “We believe that human challenge studies would be feasible and informative in the coming months,” said vaccologist Adrian Hill, involved in the development of the corona vaccine ChAdOx1. “A scientifically, ethically and logistically well-designed challenge study enables us to gain a better understanding of virus transmission and immunology and to test the required vaccines and treatments,” added Nadine Rouphael,
The idea doesn’t come out of the blue, of course. Scientists have been playing with it for much longer. And there has also been a lot of thought about what such COVID-19 focused challenge trials should look like. As published in May in the journal Science already a study in which researchers on the ethical aspects bend. And the World Health Organization has already let it go . Whether the step will actually be taken? That remains to be seen. Earlier, Dr. Collins, the man to whom the open letter is addressed, already announced that challenge trialslying on the table. Not to actually get started with it, but as a point of discussion. One thing is certain: with this open letter, that discussion has once again gotten started.