Arguments against human challenge experiments

1. There is a significant risk of serious harm and death to participants.

   Even if participants are recruited from relatively low-risk demographics, and quality medical care provided, it is likely given the numbers of participants needed for these studies that some of them will become seriously ill and there is a non-negligible possibility that some of them will die. As well as the direct effects of COVID-19, there are the possibilities of adverse reactions to the vaccine candidates, and also a possibility that the vaccine may result in making an individual’s response to COVID-19 more severe. It could be argued that conducting these experiments knowing these risks does not adequately respect a person’s right to life and the sanctity of human life itself.

2. The experiments may not result in a useable vaccine.

   While it is almost certain that some of the participants will experience harm during the experiments, it is far from certain that the research will yield a viable vaccine. As with all research, the results are unknown before the research is conducted and many medicine candidates do not successfully pass phase II and phase III testing.4

3. It may be impossible for an individual to truly give free and informed consent.

   A potential participant may experience psychological pressure as a result of their own fear or desire to make a social contribution, real or perceived pressure from friends, or a potential societal pressure to speed up vaccine development. It could be argued that this pressure may be to such an extent that it would preclude the possibility of an individual voluntarily giving their consent.

4. Conducting these experiments may damage the reputation of research and researchers more generally.

   History has many examples, particularly from the 20th century, of human experiments that were conducted in ways that are currently regarded as seriously unethical.5 It is possible that society, either now or in the future, may reflect negatively on any human challenge experiments conducted that have a significant human cost. This may lead to a long-lasting diminishing of public trust and confidence in research and researchers.

5. These experiments may be the start of a slippery slope.

   Even in recent history, such as with the Zika virus, proposals for human challenge experiments have not been considered ethical.6 If we allow such experiments now, it could make it easier in future situations with a less substantial risk to society to authorise potentially unethical experiments.

Counterarguments and potential mitigation strategies

A utilitarian perspective would regard the potential benefits to large numbers of people from a quicker-developed vaccine to outweigh the likely harms caused to a smaller number of people.7

A Kantian perspective may regard vaccine challenge studies as violating the second formulation of the categorical imperative as it would involve using the humanity of a participant merely as a means to an end.8 However it could be argued that this takes insufficient account of a participants’ ability to voluntarily consent to use their humanity in a sacrificial self-determinative way. Indeed as Wertheimer9 argues, ‘one’s choices may have moral value only if they are made autonomously, and so if we want people’s lives to have positive moral value, we need to provide the space for them to make choices for themselves’. Elsewhere,10 he expands on the idea that it may be morally praiseworthy for a person to participate in a study where the expected personal risks outweigh the expected personal benefits because of the anticipated benefits to others, and rejects the argument that such studies amount to a form of social conscripting and that slower scientific progress is always a morally necessary price to pay.

A virtue ethics approach while valuing the intent to do good would become more complex when faced with the issue of whether conducting experiments with a non-negligible risk of serious harm or death to individuals denigrates the value of an individual, and harms humanity through the consequent moral failing. The philosophical objections raised by the intrinsic value of a human argument could potentially be mitigated by ensuring that consent was truly obtained voluntarily, after appropriate disclosures by researchers, and by individuals with the capacity to so consent.

1. Addressing the risk of harm to participants.

   • As society we already permit individuals the freedom to make choices that pose significant risks to their health, for example smoking or riding a motorbike. We also permit them to voluntarily engage in occupations that carry with them a non-negligible risk of serious harm or death, such as astronauts or soldiers. It is not uncommon for a society to ask soldiers to go to war where there is significant likelihood of serious injury or death and the outcome of their work is uncertain. Indeed, there have been many medical trials in recent years that have resulted in some harm to participants,11 although the risks were generally smaller than they likely would be in a COVID-19 human challenge study.

2. Addressing the potential of no useable vaccine.

   • While it is true that any particular vaccine candidate studies may result in no viable vaccine, there is also a significant chance that it will result in one and consequently likely result in saving a very large number of lives.

3. Addressing the validity of consent.

   • It is impossible for any human to be totally devoid of the effects of individual, interpersonal and societal pressures, both conscious and subconscious, when considering the voluntariness of any consent. It could be argued that it actually withdraws from a person’s humanity and autonomy to deny them the opportunity to offer their consent to partake in research that could result in such a potentially large societal benefit. While part of the roles of societies and the law may be to protect people from themselves, their roles are also to permit conditions where a person can freely live and express their autonomy. The negative effects of COVID-19 are widely understood by likely participants, at least in broad terms, due to the media they are likely to have already consumed. Research, particularly on any long-term effects of COVID-19, is necessarily at an early stage and so for a participant to be fully informed can reasonably be interpreted as being made aware, in terms that they understand, of the currently understood risks and benefits at the point of making a consent decision.

4. Addressing reputational risk.

   • It is always possible that future humanity will look back on a decision to proceed with an experiment and reflect negatively on it. It is also possible that future humanity could reflect negatively on a decision to not conduct such experiments, or to not put sufficient efforts into assessing the possibilities of such experiments. Public confidence in researchers and the research process could be undermined if experiments with such great potential benefits were not undertaken, and ethics approval processes not adapted to be conducted at great speed while remaining robust.

5. Addressing the slippery slope.

   • Slippery slope arguments in general have been extensively considered,12 and when applied in this context they rely on an assumption that it would be a change in ethical standards to permit COVID-19 human challenge experiments in the current context. It could however be argued that to allow such experiments would not be changing our ethical standards, merely applying them to this new context. There are key differences in the contexts of, for example, Zika research and COVID-19, particularly in the gravity of threat they pose to society. Shah et al’s6 key question when ethically assessing proposed human challenge studies remains the same, namely ‘are the risks reasonable, minimized, and justified by the potential social value of the trial?’—it may be that the answer to this question is different in this case.

   • The ‘reasonableness’ of a risk and the ‘potential social value’ of a study are ordinary English words and will require interpretation by those in authority.

Guidance for regulators, researchers and ethics committees

Below is a non-exhaustive list of considerations when designing and assessing the ethical implications of human challenge COVID-19 studies.