Challenge trials and tribulations- what’s next in the race to a SARS-CoV-2 vaccine?


‘Challenge trials’, where healthy volunteers are infected with a virus, are a mainstream tool in approaching vaccine development for diseases such as malaria, typhoid, or flu. However, the World Health Organisation’s (WHO) guidance on using challenge trials for the development of a Covid-19 vaccine has been received with some controversy, principally due to the lack of available knowledge on the virus. If the ‘safe dose’ of Covid-19, which has not yet been established, is exceeded, it poses serious risks to the volunteers. No fail-safes to the trials have been developed.

If the ‘safe dose’ of Covid-19 is exceeded, it poses serious risks to the volunteers

However, the alleviation of the mortality rate associated with the pandemic is dependent on the development of effective and safe vaccines that can be rapidly distributed. With the death rate reaching 430,000 globally at the time of writing, the estimated 1.5 years until vaccine rollout is daunting, especially when you also consider the economic and sociological impacts that lockdown has caused. Assessing the safety of a vaccine in the placebo phase of testing is what consumes a significant proportion of time, and involves following several thousand participants over several months to assess differences in the frequency of disease between vaccinated and control groups. 

The study us restricted to young, healthy people between the ages of 18 and 30

As the pandemic progresses, there is a risk of progress halting completely as the infection rates drop in some areas, therefore preventing participants from becoming infected naturally. Human challenge trials, under the eight criteria that WHO have outlined, could accelerate vaccine development, and increase their efficiency. These eight criteria are essential to running an ethical challenge trial, including soliciting ‘rigorous informed consent’ from participants, and restricting the study to young, healthy people between the age of 18 and 30.

Consent in medical trials raises complex and difficult issues, even when potential participants are confronted with the explicit risks they face. ‘Optimism bias’ is likely to occur, where participants underestimate the harm that could come to them, and how probable this is to occur. Furthermore, fully informed, rigorous consent is not completely possible, as the pathogenesis of Covid-19 is not well understood, so participants must be kept current and knowledgeable as more discoveries concerning the virus arise, and be given the option of retracting their consent. Caution is paramount when approaching challenge trials, considering the lack of rescue therapy available. The fine line between causing illness and severe illness could be established through dose escalation studies, though the resultant dose would still pose an uncertain level of risk to participants, and critics of the trials say that without such rescue therapy, a trial would be impossible to launch.

Critics of the trials say that without a rescue therapy, a trial would be impossible to launch

The guidelines outlined by WHO for challenge trials state that in the absence of an effective treatment the risk falls “within acceptable upper limits” for this research and specifies steps on how these trials may be deployed. This guidance has therefore sparked interest in those involved in vaccine development for Covid-19, and triggered the launch of efforts to ready challenge trials, such as through campaigns like “1DaySooner”, which aims to demonstrate public support for challenge trials. Although these trials are riskier than other, more rigorously tested ones, the unprecedented circumstance of a global pandemic must be taken into consideration. Efforts in developing vaccines need to move urgently to prevent an unnecessary loss of life, especially as the world begins to emerge from lockdown and open up once again.

Image: Emma Jesperson

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