HOW RISKY ARE CHALLENGE STUDIES?
Overall, the same ethical requirements that govern all medical research – obtain informed consent, minimise harms to participants, ensure scientific validity, receive appropriate institutional approvals – also apply to challenge studies.
In a context where exposure to an infectious agent is integral to study design, harm minimisation is especially important. Specific mechanisms include careful selection of participants who are least likely to be badly harmed by infection; close monitoring of symptoms and quick access to treatments; and keeping participants in a closed environment until they are no longer infectious and are unlikely to spread the disease to others.
Informed consent is also absolutely essential. While there are some other contexts where consent may be waived, only competent adults who provide consent may be enrolled in challenge trials. In this way, participants can evaluate and endorse for themselves whether they feel comfortable with being exposed to an infectious disease, in view of the potential social benefits and knowledge such studies might bring.
Because participants typically must remain in a contained environment for days or even weeks on end, participants are usually paid a substantial amount as compensation for their time and inconvenience.
Some may be concerned that such substantial payments could distort participants’ judgments, but this risk can be minimised with robust consent provisions. Moreover, given how great a commitment a challenge study involves, it would arguably be unethical not to pay participants a substantial amount.
Engagement with relevant communities and potential participants is also a core part of challenge studies. Indeed, the grassroots organisation 1Day Sooner emerged during the COVID-19 pandemic and quickly garnered interest from thousands around the world willing to risk their own health in a challenge trial if it would contribute to the acceleration of effective treatments and vaccines for COVID-19.
1Day Sooner has since pivoted to advocate for trials in a range of other infectious diseases. Its success reflects the importance of capturing the sentiments of potential participant voices in the development and oversight of challenge trials.
This is not to say challenge trials are without risks. However, the result of the design criteria for conducting modern-day challenge trials is that the risk that a participant could die or suffer any serious long-term injury has been reduced to very, very close to zero.
Indeed, a review of hundreds of challenge trials from 1980 to 2021, involving more than 15,000 participants, found no deaths at all in that period, and only a fraction of a per cent of participants experienced serious adverse events. This is a comparable or even more favourable risk level than that of many early phase clinical trials of novel therapeutics.
In short, with careful design and appropriate oversight, a challenge study can not only be ethically acceptable but is also an important component of a larger toolbox in combatting infectious diseases.
G Owen Schaefer is Assistant Professor at the Centre for Biomedical Ethics at National University of Singapore’s Yong Loo Lin School of Medicine, while Jerry Menikoff is Professor of Bioethics in the same institution. Barnaby Young is Head, Singapore Infectious Diseases Clinical Research Network at NCID.
