Recently there has been lots of media coverage and discussion about the first COVID-19 human infection challenge vaccine study in the world, planned in the UK. Human infection challenge vaccine studies involve the deliberate infection of healthy volunteers. These studies can be particularly valuable for testing vaccines and can speed up the development of new vaccines.
How do challenge studies work?
When trialling COVID-19 vaccines they need to be tested on a large number of people because not all the vaccinated people will get exposed to the virus. A challenge trial makes it quicker to check on a much smaller number of people whether the vaccine protects when people are deliberately infected with the virus.
Human infection challenge vaccine studies are often used to test vaccines. Generally, in challenge studies there is an existing treatment for the infection, so if the vaccine being tested doesn’t work, then treatment can be given. With COVID-19, although a lot has been learnt in a short time, there are still things that we don’t know. We now have some treatments, but they are not always effective and some people appear to be more at risk of severe illness than others. Any challenge study would need to use as much of the evidence as possible to manage the risks.
Considering the ethical issues
Any challenge study submitted to the HRA would require review by a Research Ethics Committee.
The role of a Research Ethics Committee is to ensure that, where possible, risks are minimised, and that participants can make a free and informed choice about accepting any remaining risks before getting involved in the trial. In preparation for the proposed COVID-19 human infection challenge vaccine study we’ve established a Research Ethics Committee of experienced members from around the UK, some of whom have reviewed challenge studies before.
This special committee has been recognised by the United Kingdom Ethics Committee Authority and contains a balance of expert and lay members, as do our other committees. We’re providing special training, developed using guidance from the World Health Organisation, to this group of Research Ethics Committee members. The committee will consider the purpose of the study, the research team’s experience, how patient and participant views have been included in the design, the balance of the potential risk against the possible benefit, how participants will be selected, how the potential harm would be addressed, whether potential participants will have information that allows them to make an informed choice, and whether payments for participating are fair.
Any application for a COVID-19 human infection challenge vaccine study will be considered under our COVID-19 fast-track process, to ensure important research starts as soon as possible. However, we follow the same processes and apply the same ethical standards for COVID-19 research as we do all other research.
Like all our meetings at the moment, the Research Ethics Committee will meet virtually, and the research team will be invited to attend to answer questions and discuss their application. After the meeting, the Research Ethics Committee may request changes or further information. The research team can respond and the final decision – of a favourable or unfavourable opinion – is made after that and published on our website within three days.
Stages of research
A human infection vaccine challenge study for COVID-19 would consist of several stages. The first part is to screen volunteers to select people who meet the specific criteria set out in the study protocol. These volunteers will then choose whether to proceed to one of the next stages. The second phase is to work out the lowest possible dose of virus that would prove that the vaccine works, by deliberately giving some of the volunteers measured amounts of virus, and checking for detectable signs of infection. The third stage then tests one or more possible vaccines by giving a separate set of volunteers a test vaccine followed by a dose of virus, and then testing for infection. Each of these phases will need a favourable ethics opinion before it can proceed. The third stage where vaccines are tested would also need Clinical Trials Authorisation from the Medicine and Healthcare products Regulatory Agency (MHRA).
Terence Stephenson, Chair of the HRA, said: “There’s very little research that carries zero risk. A challenge trial application would have to make the argument that the benefits to society greatly outweighs the risk and that evidence or data could not be achieved in a simpler or safer way.”
We protect and promote the interests of patients and the public in health and social care research. Challenge studies require careful consideration, but we are the ethics experts and our Research Ethics Committees have the skills, experience and established methods for considering this kind of research. We’re playing a crucial part in COVID-19 research: helping vital research start quickly but ensuring it maintains high ethical standards.