A team of American scientists proposed, in an article published on March 31, to speed up the normal procedure for validating a candidate vaccine by voluntarily exposing healthy individuals to Covid-19.
Quick. As the Covid-19 pandemic progresses all over the world, speed has become the main watchword for doctors and scientists, even if it means taking liberties with procedures. In France, Professor Didier Raoult caused controversy by praising the efficacy of hydroxychloroquine and azithromycin for treating patients contaminated with coronavirus when large-scale tests for this drug had not yet been done.
Far from the media noise around chloroquine, an American team put forward another proposal which makes the scientific community uncomfortable: a “Human challenge” which consists in contaminating a hundred healthy volunteers, some of whom would have received a candidate vaccine, that is to say at the advanced testing stage, in order to speed up the process of making treatment available to the general public.
Save several months
Their experience, detailed in an article published on March 31 by the Journal of Infectious Disease, was described as “provocative” by the highly respected scientific journal Nature. It would make it possible to take an important shortcut compared to the traditional procedure of validation of a vaccine, but “the volunteers are likely to be seriously ill and, some, could even die”, recognizes Nir Eyal, the director of the Center for Population- level Bioethics of Rutgers University (New Jersey) and main author of this study, interviewed by Nature.
This approach takes, of course, the first two phases of testing the usual procedure – in the laboratory, then on animals -, but diverges sharply during the human experiment, which is the longest stage. Traditionally, the candidate vaccine has been administered on a large scale, to a population of around 3,000 people. These individuals are then released into the wild and it is observed whether those who received the treatment are more resistant to the disease than those treated with a placebo. The big difference from the approach advocated by the study authors is that it is not the doctors who directly expose the volunteers to the disease.
“In this epidemic, many of the participants in a standard procedure for validating candidate vaccines will, once back in their environment, seek to minimize the risk of being contaminated and it will probably take a very long time to obtain scientific results actionable, “says Nir Eyal. Experts estimate that a vaccine would not be available for about eighteen months by following the rules to the letter. The researcher at Rutgers University judges that his approach would save “several months”.
A saving of time which can prove to be crucial. “The problem that often arises is that by the time a vaccine is available, the epidemic is over and we no longer know how to assess its effectiveness,” said Dr Anne-Marie Moulin, doctor and associate of philosophy, contacted by France 24. This is what happened during the 2014 Ebola epidemic. Without being able to test the candidate vaccines in the face of the epidemic, doctors cannot fully assess the weapon which is vital in return of the virus ..
“Nuremberg rules” at Covid-19
Historically, “human challenges” are far from unprecedented. “It is only relatively recently that vaccine studies have become standardized, being extremely demanding as regards the ethical conditions for carrying out them in order to minimize the risks as much as possible,” recalls Anne-Marie Moulin. In the early 1970s, a French hepatitis B vaccine was first tested on volunteers among hospital staff most exposed to this virus.
Despite these advantages and the tradition which would militate in favor of this risk taking with the health and the life of volunteers, this type of experimental approach encounters serious ethical obstacles. It is no coincidence that the “Nuremberg rules” – a moral code for scientific research established after the trial of Nazi doctors in 1946 – specifically banned human experiments “if there is a reason a priori to think that these clinical trials can kill or inflict debilitating lesions “.
More nuanced, the Council for International Organizations of Medical Sciences – which reports to the World Health Organization (WHO) and Unesco -, balances the risks for volunteers with the expected benefit for the discovery society. of a treatment. But this NGO specifies, however, that these “human challenges” are to be excluded in the case of diseases “like anthrax or Ebola, whose mortality rate is very high”.
Which does not seem to be the case with the Covid-19. However, even if the current pandemic could enter ric-rac within the framework of what is ethically acceptable, it is still necessary that the procedure devised by the American researchers minimize the risk run by the participants. Nir Eyal thinks he has succeeded. The hundred volunteers would be selected from young adults, between 20 and 45 years of age, who are the least likely to suffer from the life-threatening complications of Covid-19. They come from areas very affected by the coronavirus epidemic, which means that they are naturally very likely to be contaminated. Extensive medical examinations would ensure that none of the participants had any known comorbidities or conditions that could make Covid-19 more dangerous, such as breathing problems. These volunteers should also be given priority to obtain the best possible treatment in the event of a complication after exposure to the coronavirus.
Following the experiment, participants will be kept away from the rest of the population for fourteen days, which corresponds to the time during which they can be contagious, in order to minimize the risk of contamination for their loved ones. For Nir Eyal, “curiously, it might even be safer for these individuals to participate in this study, rather than waiting for a probable contamination and placing their hopes in the general health system”.
The problem of informed consent
Dr. Anne-Marie Moulin, who was director of the deontology and ethics advisory committee of the Research Institute for Development, considers the scientific aspect of the protocol interesting, but she doubts one last essential point of this type of clinical study: the informed consent of the participants. Nir Eyal ensures that each participant must be fully aware of the risks and accept them, but he remains “very vague on certain aspects of the selection of candidates,” notes the doctor. Thus, “we know that they must be in good health, but it is nowhere said how this state of health will be evaluated,” she regrets.
It would also be important, she said, to know more about the socio-economic background of the candidates. If only to ensure that they have the scientific culture to understand all the implications of such a study. We should also be able to assess their motivations. There is, in fact, a risk in this type of experience that certain individuals “pushed by the desire to have a quarter of an hour of glory for having participated in the study which made it possible to find a vaccine, seeks to conceal health concerns, “said the French scientist. According to her, “the way in which the selection of candidates is presented is summary”, which is ethically debatable, because they are the ones who will be on the front line.
But beyond these moral considerations linked to the protocols of the study itself, the proposal of Nir Eyal and his team poses a crucial question to society: that of “weighing the individual risk compared to the service rendered for the common good in times of crisis, “concludes the doctor-philosopher. And given the urgency of the health situation, she risks having to quickly respond to it.
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