The World Health Organisation (WHO) has published a report of a joint Health Research Authority/WHO workshop on the ethics review of COVID-19 human challenge studies. We look back on the HRA’s role in this ground-breaking journey: from application, to approval, to results and beyond.
Back in 2020 the media was buzzing with news of cutting-edge trials. ‘Research offers hope for coronavirus,’ said the government’s Chief Scientist, Sir Patrick Vallance. We heard that the world’s first COVID-19 human infection challenge study was being planned in the UK.
Human challenge studies involve the deliberate infection of healthy volunteers. New vaccines need to be tested on a large number of people. A challenge trial makes it quicker to check on a much smaller number of people whether a vaccine protects when people are deliberately infected with the virus so these studies could speed up the development of treatments to fight against COVID-19.
This type of research is not unheard of, but the COVID-19 challenge study was different. 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. This wasn’t the case with coronavirus.
While there was no shortage of volunteers to take part in challenge studies if needed, it was clear that the ethical issues raised by allowing people to be deliberately infected with COVID-19 needed careful consideration by the HRA’s Research Ethics Committee members.
As our Chair Professor Sir Terence Stephenson said at the time: ‘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.’
The route to approval
Any challenge study taking place in England needs to be reviewed 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.
Knowing an application for the proposed COVID-19 human infection challenge vaccine study was likely, we began to prepare.
Setting up the committee
In preparation for the challenge study application, a specialist Research Ethics Committee was brought together to review the research proposal, made up of experienced members from around the UK, some of whom had reviewed challenge studies before. It was chaired by Stephanie Ellis.
The specialist REC included 18 experienced members from existing RECs from a range of professional backgrounds and nationalities (12 from England, three from Scotland, two from Wales and one from Northern Ireland). The committee included 12 expert members (people with relevant formal qualifications or professional experience that can help the REC understand particular aspects of research proposals), and six lay members (members of the public).
This special committee was recognised by the United Kingdom Ethics Committee Authority and members were given special training, developed using guidance from the World Health Organisation, which included the WHO’s key criteria for the ethical acceptability of COVID-19 human challenge studies.
Challenge studies require careful consideration, but the REC was well qualified to do this.
Considerations
When the application then arrived from Imperial College London in early 2021, our specialist REC sprang to work. Its job was to consider the purpose of the study, the research team’s experience, how patient and participant views had been included in the design, the balance of the potential risk against the possible benefit, how participants would be selected, how the potential harm would be addressed.
Another crucial consideration was to consider whether potential participants would know enough to make an informed choice about whether they wanted to take part, and whether payments for participating were fair.
Approval
After raising some questions with the research team and receiving further information, the research ethics committee gave a favourable opinion for the world’s first COVID-19 human infection challenge study on 16 February 2021.
The research
Conducted by Imperial College London in partnership with hVIVO (a contract research organisation that specialises in human challenge studies), the research took place at the Royal Free Hospital in London.
The world’s first COVID-19 human challenge study involved 36 participants having drops of fluid containing the virus into their nose. 18 became infected, confirmed by PCR testing, and 16 showed symptoms. All 36 participants finished the study healthy.
Study data, published in a preprint in January 2022 and widely reported, helped us learn more about the virus’ progression. The study has generated valuable clinical insights including the length of time between being infected and displaying symptoms, information about how the virus is shed by people, and how well lateral flow tests work.
Next steps
The success of the first COVID-19 challenge study paves the way for even more exciting research in the future.
The HRA/WHO joint workshop report published this week is based on a roundtable workshop with the HRA, members of the specialist REC and members of the WHO Working Group that developed the Guidance on Human Challenge Studies in COVID-19. It concludes that the approach the HRA took represented a model of good practice for ethics review of novel, complex and sensitive study designs. The WHO suggests that the combination of international guidance and experience in the UK of the delivery of COVID-19 human challenge studies may help to promote public confidence in human challenge research.