Researchers at Oxford University, in the UK, are seeking volunteers to participate in human challenge studies. These are carefully controlled experiments which involve deliberately infecting volunteers with a pathogen to analyse the effects of the infection. It could be important for future vaccine development.
While such studies are highly controversial, it is arguably necessary in order to study the human immune response and crucially, it may improve the effectiveness of future vaccines.
In 2021, the UK was the first country to approve a human challenge trial of Covid-19. Since April, researchers have been working on a low-risk dose of the coronavirus for human trials (phase 1). Vaccinologist Helen McShane led her Oxford team in testing what is the minimum amount of virus required to trigger an immune response.
The virus is rather different today as it has since evolved into various variants. As McShane said, “We have learned a lot about Covid over the past two years, but the emergence of new variants means that we will probably have to keep refining the vaccines. If we know what level of immune response we need the vaccine to induce, it will make future vaccine development much quicker and much more efficient.”
This second phase of the trial will last for one year. The researchers are using the original strain of the virus from Wuhan. Participants will be infected with SARS-CoV-2 through nasal drops. They will be infected with standardised dose of virus and they will be observed as to how their immune systems respond to the virus. There will be at least 17 days of quarantine for the volunteers in a special section of the hospital.
But what about ethical safeguards for these volunteers? Can allowing volunteers to be deliberately infected with a potentially lethal disease to develop a vaccine be conducted in an ethical fashion? Has reasonable care been given to maximise the potential benefits of the study and minimise the risks of harm to the volunteers? Is the informed consent process for the participants sufficiently rigorous?
Only younger healthy participants in the experiment should be recruited. Oxford is recruiting just volunteers between 18 and 30 years old who are in very good health.
But even younger people are taking a risk. All clinical researchers remember the fate of an 18-year-old American, Jesse Gelsinger. He died in a gene therapy trial in 1999. If a participant falls seriously ill with Covid-19, there is currently no cure. In the Oxford study, the volunteers will have to undergo various tests such as MRI heart scans and CT lung scans. Anyone who develops symptoms will be given Regeneron’s monoclonal antibody treatment, Ronapreve.
High-quality informed consent is crucial. This can’t be taken for granted. Apart from medical experiments in Nazi death camps, there have been many trials in which the patients were coerced, exploited, or deceived. Naturally, participation in the Oxford trials is entirely voluntary. But it is critical to ensure the participants really understand all the risks from the outset. This could be facilitated by requiring them to sit for an examination to test their comprehension.
Continuous informed consent is also critical since fresh developments arise from time to time, eg, greater knowledge of the virus and its ways of transmission.
Long-term monitoring and follow-up of the participants is also crucial. In the Oxford study, there will be five follow-up appointments after the participants are discharged.
In the Oxford studies, volunteers will receive a relatively large sum of money; £4,995 (around $A9,500) as compensation for lost time and inconvenience. It seems only fair. However, for someone in straitened circumstances, the cash might undermine informed consent. Ethicists say that payment for participation in studies should be modest — but Oxford’s seems unusually generous.
In the light of the urgency of developing a vaccine and the potentially catastrophic consequences for the whole world of having to live without one, human challenge experiments are probably worth the risk. But they have to be conducted with scrupulous attention to all of the ethical issues in a constantly changing environment.