Human Challenge Vaccine Trials

i. Introduction

The dilemma of whether “human challenge” trials should be carried out for the development of a
COVID-19 vaccine is of great relevance and dispute. The implications, moral and medical, are under
great scrutiny so that a verdict may be reached on whether pursuing these trials will be too great a risk
in comparison to their possible benefits. This area of research is of particular interest to philosophers
considering the necessary deliberation which must be awarded to the ethical matters of scientific
advancement, medical autonomy, and the choice one has to undertake personal risk. Support for this
case lies predominantly in the argument that the trials allow rapid development and testing of vaccine
candidates so that a secondary or tertiary inoculation can be created. Much of the rebuttal finds its
foundation in the seemingly pointless risks taken to develop further vaccines when multiple are
already successful and available. Both claims are important to examine as possible studies of this sort
are already appearing, for example in the UK, where thousands have volunteered to take part in a
clinical trial where they are exposed to the SARS-CoV-2 pathogen and then given vaccines to test
their efficacy.1

ii. The ethics of risk and the choice to take it

The potential good that “human challenge” trials can do with regard to studying the SARS-CoV-2
pathogen and developing vaccines is significant, and despite the existence of multiple effective
inoculations, the understanding we could gain and the progress towards developing secondary
vaccines is undeniably appealing to the medical community. These challenge trials simply allow us to
better understand “the biology of the disease, host immune response/and vaccine and therapeutic
development.”2 Also, with the rising prevalence of variants of concern (VOCs) and their potentially
enhanced risk, these challenge trials could introduce cross-variant examination into their research so
that we may better create countermeasures to protect populations against a wider variety of
pathogens.3 Discouraging the volunteering of informed individuals with altruistic motives from
participating in programs that will support the greater public good becomes, as Flanigan observes,
quite paternalistic, as they limit medical autonomy. She remarks that “just as adult patients
are/capable of consenting to other medical procedures, treatment, and research, they are capable of
consenting in challenge trials.”4

The rebuttal often finds its foundation in the proposition that these trials will disproportionally affect
at-risk groups and that even if there is an emphasis on researching with healthy and consenting adults,
the risk taken does not justify the potential gains. Some studies, such as one recently approved United
Kingdom, offer volunteers a monetary reward for their participation, but in doing so this encourages
the volunteering of those from lower socio-economic backgrounds, who are already impacted greatly
by the pandemic. selecting people from these groups may only serve to emphasise the structural

1
Daniel Sulmasy. “Are SARS-CoV-2 Human Challenge Trials Ethical?” JAMA Intern Med. Vol 181, no. 8, 2021, pp, 1031–
1032. doi:10.1001/jamainternmed.2021.2614
2
Amrita Sekhar, Gagandeep Kang. “Human challenge trials in vaccine development.” Seminars in immunology vol. 50,
2020, 101429. DOI: 10.1016/j.smim.2020.101429
3
Garth Rapport, et al. "SARS-Cov-2 Human Challenge Studies — Establishing The Model During An Evolving
Pandemic". New England Journal Of Medicine, vol 385, no. 11, 2021, pp. 961-964. Massachusetts Medical Society,
https://doi.org/10.1056/nejmp2106970.
4
Jessica Flannigan. “The Case for Challenge Trials.” The Ethics of Human Challenge Trials: COVID-19 and Beyond, Cato
Unbound, 2021, https://www.cato-unbound.org/2021/03/09/jessica-flanigan/case-challenge-trials/
injustices and burdens they face. 5 Therefore, informed consent and is compromised, because despite
being aware of any possible risks, volunteers may make rash decisions in participating and be
severely impacted as a result.

Though this argument has merit, the irrefutable proof is that thousands of people have volunteered to
participate in these trials, and when selecting subjects, those who are young and without any pre-
existing health conditions can be prioritised to minimise complications. Even if this were to occur, in
the context of COVID-19 and the proportion of individuals who have been vaccinated, “maintaining a
non-vaccinated placebo group” as a control for the challenge trial is ethically questionable.” 6 There
lies the ability to undertake this study with a low-risk group who can understand all of the possible
outcomes and consequences and consent, nonetheless.

The unknowns of COVID-19 are another area that causes great concern amongst those who refute
challenge trials, where the possibility for subjects to suffer ‘long COVID’ marks a problem area. This
is a severe possible side effect of contracting the virus, one that Weijer argues to warrant the necessity
of rescue medicine.7 There is no such form for any variant of COVID-19, and therefore Weijer
plausibly argues that challenge trials should not take place. He continues by objecting to Flanigan’s
paternalism argument, claiming that it should not be problematic if paternalism is justified. Thus,
knowingly exposing a participant to a virus that may cause serious harm “violates the/duty of care to
the participant”8 and, preventing such from happening is an understandable decision, and not
disrespectful.

iii. The politics of COVID-19

Ben Bramble’s central counterclaim to the need for challenge trials lies in the failures of governments
to handle the crisis in terms of distributing vaccines, ensuring apt safety measures were enforced, etc.
In surmising his argument, Bramble claims that “the fault here lies not with medical, but with
political, conservatism.”9 He continues to criticise the lack of political action, not the means by which
vaccines were developed, which by traditional standards, was incredibly fast in the face of such a vast
and rapidly growing emergency. Arguably then, it is rather the rollout and action of governments to
protect their citizens that mark the shortcomings and failures in this pandemic. 10 Bramble criticises
how these challenge trials may future preparedness by allowing governments to “take the easy way
out”11 by sacrificing a small group of volunteer subjects to potentially great dangers instead of having
the general citizenry make small concessions. Traditional vaccine trials follow the same premise
though, where a small societal cross-section takes a consenting risk to mitigate a larger and broader
sacrifice having to be made by a greater number of people. Even if the traditional trials which
5
Sean O’Neill McPartlin, et al. “Covid-19 Vaccines: Should We Allow Human Challenge Studies To Infect Healthy
Volunteers With SARS-Cov-2?” British Medical Journal, Oxford, 2020, pp. 1-3. Accessed 1 June 2022.

6
Garth Rapport, et al. "SARS-Cov-2 Human Challenge Studies — Establishing The Model During An Evolving
Pandemic". New England Journal Of Medicine, vol 385, no. 11, 2021, pp. 961-964. Massachusetts Medical Society,
https://doi.org/10.1056/nejmp2106970.
7
Charles Weijer. “SARS-CoV-2 Human Challenge Studies Should not be Permitted.” The Ethics of Human Challenge
Trials: COVID-19 and Beyond, Cato Unbound, 2021, https://www.cato-unbound.org/2021/03/15/charles-weijer/sars-cov-2-
human-challenge-studies-should-not-be-permitted/
8
Ibid
9
Ben Bramble. “Challenge Trials are a Poor Substitute for an Effective Pandemic Response.” The Ethics of Human
Challenge Trials: COVID-19 and Beyond, Cato Unbound, 2021,
https://www.cato-unbound.org/2021/03/11/ben-bramble/challenge-trials-are-poor-substitute-effective-pandemic-response/
10
Ibid
11
Ibid
Bramble advocates for are conducted in combination with a successful political response and enacting
of public safety proceedings, this does not nullify any benefits which could be found in a challenge
trial. In Flanigan’s response to Bramble’s objection, she suggests that they may “have accelerated the
pace of vaccine development/[made] it easier to develop vaccines tomorrow,” 12 thus saving lives to
outweigh any cost which the trials themselves may pose.

iv. Evaluation and conclusion

I do agree with Bramble and his discussion of political failures in response to the outbreak, spread,
and action taken to deal with the evolving COVID-19 pandemic. But this does not warrant a complete
discounting of the potential advantages of utilising human challenge trials which Flanigan outlines.
Although Weijer makes a sound point about how prohibiting risky volunteering for these trials is not
necessarily paternalistic given their inherent dangers, the reality is that more comparatively risky
medical procedures are undergone by consenting adults, which raises the principle of ‘risk parity.’ I
believe that scientific risks are to be considered no differently than those taken in other contexts,
where altruists are embraced for the challenge trials, as they present great benefits for society. 13 And
in an even more pragmatic consideration of trials, philosophical issues aside, they will likely allow an
influx and accumulation of important epidemiological and virological knowledge which will prove
central to the better handling of any future outbreak. Therefore, I am driven to support the clinical
application of human challenge trials for the COVID-19 virus in the testing of vaccine efficacy
against new variants so that we may better understand the disease as well as produce secondary and
tertiary inoculations for the future.

Word count: 1457

Bibliography
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Trials: COVID-19 and Beyond, Cato Unbound, 2021, https://www.cato-unbound.org/2021/03/11/ben-bramble/challenge-
trials-are-poor-substitute-effective-pandemic-response/

12
Jessica Flannigan. “Reply to Bramble.” The Ethics of Human Challenge Trials: COVID-19 and Beyond, Cato Unbound,
2021, https://www.cato-unbound.org/2021/03/25/jessica-flanigan/reply-bramble/
13
O’Neill McPartlin, Sean et al. “Covid-19 Vaccines: Should We Allow Human Challenge Studies To Infect Healthy
Volunteers With SARS-Cov-2?” British Medical Journal, Oxford, 2020, pp. 1-3. Accessed 1 June 2022.
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https://www.cato-unbound.org/2021/03/25/jessica-flanigan/reply-bramble/

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O’Neill McPartlin, Sean et al. “Covid-19 Vaccines: Should We Allow Human Challenge Studies To Infect Healthy
Volunteers With SARS-Cov-2?” British Medical Journal, Oxford, 2020, pp. 1-3. Accessed 1 June 2022

Rapport, Garth et al. "SARS-Cov-2 Human Challenge Studies — Establishing The Model During An Evolving
Pandemic". New England Journal Of Medicine, vol 385, no. 11, 2021, pp. 961-964. Massachusetts Medical Society,
https://doi.org/10.1056/nejmp2106970.

Sekhar, A and Kang, G. “Human challenge trials in vaccine development.” Seminars in immunology vol. 50, 2020, 101429.
DOI: 10.1016/j.smim.2020.101429

Sulmasy, D. “Are SARS-CoV-2 Human Challenge Trials Ethical?” JAMA Intern Med. Vol 181, no. 8, 2021, pp, 1031–1032.
doi:10.1001/jamainternmed.2021.2614

Weijer, C. “SARS-CoV-2 Human Challenge Studies Should not be Permitted.” The Ethics of Human Challenge Trials:
COVID-19 and Beyond, Cato Unbound, 2021, https://www.cato-unbound.org/2021/03/15/charles-weijer/sars-cov-2-human-
challenge-studies-should-not-be-permitted/