31 Jul 2020
Just at the point where vaccine trials are showing promise, levels of infection circulating in the general population in the UK are relatively low. This is obviously good news from many perspectives – but makes the next stage of testing more difficult. Is one possible answer human challenge trials?
Early-phase vaccine trials for COVID-19 in the UK are beginning to report results, suggesting a strong immune response in participants and a good safety profile. The next stage will be larger Phase III trials, recruiting a much more diverse cross-section of the population to explore whether a vaccine offers ‘real-life’ protection against the virus (and if so, for how long).
A common problem encountered in research during epidemics is that of timing: even impressively expedited vaccine studies may reach this stage just at the point when the first wave of infection is coming under control. This makes it much harder and slower to find out whether the vaccine offers protection, because research participants are just so much less likely to be exposed to infection.
One answer to this dilemma is that of international partnerships working across a number of countries at different points in the epidemic wave – as long as due attention is paid to the need to ensure that any successful vaccine will be as available and accessible in partner countries as it will be in the UK. An alternative approach, however, to vaccine development – already used for research in pandemic flu and malaria, for example – is that of ‘human challenge studies’ where participants are deliberately infected with the disease in question to see if the vaccine protects them. Such studies can produce much quicker results (although the time taken to establish them, including developing the strain of virus to be used, should not be overlooked.)
Opinions differ markedly regarding what is required for such human challenge trials to be conducted ethically – and in particular whether the existence of an effective treatment against the disease is an essential prerequisite. With impressive speed, the WHO global ethics team established an expert group to offer guidance for the COVID-19 pandemic, leading to the publication in early May of Key criteria for the ethical acceptability of COVID-19 human challenge studies. The guidance neither endorses nor rejects the possibility of challenge trials being conducted in the current pandemic. Rather it sets out the following eight criteria to be considered by policy-makers and researchers when considering the ethical acceptability of specific proposals to conduct challenge studies in COVID-19:
The guidance does not include a specific requirement for an effective treatment for COVID-19 to be available before challenge studies are considered, requiring instead a rigorous assessment of the risks and benefits. Some experts in this field remain deeply uncomfortable about this. Others note how even ‘treatable’ diseases can exceptionally lead to serious harm, suggesting that the availability of treatment cannot provide a simple yes/no answer to whether or not a study can be conducted ethically. Rather, the existence of a treatment is just one aspect of the overarching issue of risk minimisation.
There is a striking level of public support for challenge trials: the organisation ‘I Day Sooner’ advocates on behalf of many thousands of people worldwide who have put themselves forward to volunteer for a challenge study. Freely-chosen willingness to take risks for public benefit (permitted as praise-worthy self-sacrifice in other parts of life – think, for example of the risks run by the life-boat service) is seen by some as sufficient to justify trials going ahead without further ado. Others highlight the limits of informed consent in such circumstances – especially given how recent empirical research has highlighted the gap between people’s expectations of involvement in challenge studies and the reality. In our own work on research ethics at the Nuffield Council, we have argued strongly that while partnership with patients and the public is a core part of ethical research, the fundamental responsibility of deciding whether risks and benefits are appropriately balanced in any proposed study remains the responsibility of researchers and ethics committees. It cannot be ‘outsourced’ to potential participants.
So what would be required for challenge studies to take place in the UK? Drawing on the WHO guidance, serious public engagement must be the starting point – both with those who advertise their willingness to be involved, and within the communities geographically close to research sites that might consider such studies. Such engagement would serve both to draw out concerns, preconceptions or misunderstandings (whether in favour or against such studies) that would inform subsequent ethical review, and help create trusting partnerships should a study in the future be given the go-ahead.
Ultimately it would be responsibility of both local and specialised ethics committees (the latter established either at national or international level) to make a judgment, based on an analysis of the best available evidence of risks, and possible benefit. Not an enviable task.