Why we agreed to review the first COVID-19 human challenge study

By Simon E. Kolstoe, Tony Lockett and Hugh Davies

Reliable information is essential for good decision making. This is particularly true when complex medical situations are combined with political and social ramifications, such as during the COVID-19 pandemic. The last two years have been revealing from the perspective of seeing how societies rely upon, but also interpret and apply, scientifically derived information.

The requirement for high quality data during the pandemic has led to considerable investment in research and subsequent discussions regarding reliability and prioritisation. While investment in certain areas such as vaccine development and addressing acute medical and social impacts of the pandemic can clearly be justified, not all research is good or valuable. Research is a complex activity, and quite often poor research design, and failure to adequately define and then test hypothesis, is the cause of considerable research waste.  Furthermore, even during the pandemic, the wider context must still be considered. There are plenty of other health challenges that are far more dangerous than COVID-19 (such as cancer and heart disease) that are still competing for funds and attention. Regardless of the pandemic situation, research efforts must still be focussed efficiently and on the right questions.

Human challenge studies, wherein human participants are deliberately exposed to a disease causing agent alongside experimental treatments, are not new. From one perspective they represent a particularly efficient and focussed scientific methodology by allowing careful control of a number of disease and treatment parameters. They are also often conducted under close medical and regulatory supervision. However, they can also be ethically contentious. In the majority of infectious disease related research treatments are tested on participants from populations who are naturally exposed to the disease. But, in challenge studies, otherwise healthy individuals are exposed to agents that may cause them long term harm. Thus, while in most research there are potential personal benefits to patients (who might otherwise have received no, or less effective treatments), challenge studies bring additional risks for almost no personal benefit to participating volunteers.

From the start of the pandemic the possibility of SARS-CoV-2 challenge studies have been discussed in this journal and elsewhere. Numerous scientific and ethical arguments have been made both for and against conducting such studies. Furthermore the theoretical benefits (and disadvantages) of such studies have varied significantly during different stages of the pandemic due to the rising and falling fortunes of healthcare systems, vaccine development (and implementation) programmes, the impact of social interventions (such as lockdowns), and more recently emerging coronavirus variants.

This creates a challenge for both researchers as they design studies, but also ethics committees asked to review and assess challenge studies. In our paper published in this journal we describe the ethics review of the first human challenge study approved in the UK (and possibly the world). This was the first time that the ethical arguments moved from the theoretical to the practical, certainly in the context of COVID-19. We describe how the committee used existing guidance and how this was synthesised into a robust, and defendable, ethics decision. The process was not straightforward, and could be viewed as contentious by some, but we believe the review was conducted with the best interest of patients, and our wider communities, at the heart.

Paper title: The UK Research Ethics Committee’s review of the global first SARS COV 2 Human Infection Challenge studies

Author: Hugh Davies on behalf of the specialist committee

Affiliations: UK Health Research Authority

Competing interests: None

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