Last updated December 11, 2020

Objections to COVID-19 Human Challenge Trials

[This 2020 page is kept for reference purposes. 1Day Sooner stands by its advocacy for COVID-19 human challenge studies, but the information below may be outdated does not necessarily represent our current thinking.]

COVID-19 human challenge trials are not a silver bullet. There are a number of objections and limitations to these trials that have been raised by scientists and bioethicists that must be grappled with by all stakeholders. Below, you can find six common arguments against challenge trials, replies from the 1Day Sooner team, and resources to learn more.

Lack of a Rescue Therapy

Previous human challenge trials involved diseases for which there was a very low risk of death or an approved rescue treatment. By contrast, COVID-19 has a significant mortality rate and there is no effective cure. Conducting a trial in which a healthy volunteer might needlessly lose their life in the context of a research trial goes against the fundamental principle of medical ethics, which is to do no harm.

  1. The risk of death for young healthy volunteers is very low, and on par with similar risks in medical context. In the absence of an approved rescue treatment, the short-term risks of death from COVID-19 for the young healthy volunteers who would take part in a SARS-CoV-2 challenge trial are lower than societally accepted risks like kidney donation. Additionally, we allow nurses and doctors who are up to 12x as likely to contract COVID-19 than the general population to show up to hospitals to save lives – even if they themselves are in their 50s or 60s, and are at significantly elevated risk. If these risks are allowed in other contexts without an approved treatment, they should be allowed in challenge trials if the latter can save lives.
  1. The World Health Organization (WHO) argued that a rescue therapy is not a prerequisite for a challenge trial. The WHO wrote in May 2020 that challenge trials would incorporate treatments if and when available, which could easily be before a challenge trial is launched, but the WHO suggests that is not a prerequisite, it is a mitigation which can be used alongside other risk-mitigation techniques.

Long-Term Risks

There is growing evidence that COVID-19 causes considerable long-term negative health effects. Some studies show that these sequelae can affect asymptomatic carriers and low-risk demographic groups. Robust informed consent requires that volunteers understand the full range of risks from a COVID-19 human challenge trial, and this is impossible in the status quo. The possibility of long-term sequelae mean that challenge trial participants could face significant lifelong health consequences from their involvement in a trial.

  1. Potentially significant long-term COVID-19 sequelae affect both sides of the risk/reward calculus. Potential long-term sequelae increase risks to potential trial participants, but they also raise the stakes of ending this pandemic sooner by making COVID-19 even more devastating in the long-run. We think it is preferable that young healthy volunteers with access to excellent medical care incur the long-term risks of COVID-19 rather than vulnerable populations who are at even greater risk.
  1. Uncertainty does not necessarily preclude informed consent. Long-term risks were not known during the first kidney donation in the 1950s, and they are still not known by healthcare workers who place themselves at greater risk everyday by showing up to work. Yet these groups’ choice to accept large and uncertain long-term risk is legitimate and justifiable toward the end of saving lives. We agree that volunteers would need to understand that there are considerable and uncertain risks in a SARS-CoV-2 challenge trial, but many wish to participate even understanding this. Given that understanding, they should be allowed to participate in such a trial if there is a chance that by volunteering, they may help shorten a pandemic that is disproportionately hurting vulnerable populations without access to medical care.

Applicability of Data

Data gathered from a COVID-19 human challenge trial would have such limited applicability to vaccine and treatment development that the benefits of such a trial would not outweigh the risk. Since a challenge trial would include only young and healthy trial participants, the resulting data would not necessarily be generalizable to older immunocompromised people– the exact demographic that is bearing the brunt of this pandemic.

  1. Testing on young healthy volunteers may produce generalizable data. It should not be taken for granted that indicating vaccine efficacy among young healthy populations would not be applicable to older immunocompromised populations. A substantial minority (8 of 19) panelists with the World Health Organization believed that “efficacy results in young adults in a challenge model will predict efficacy in elderly and high-risk adults.”
  1. Even a vaccine that only works for young healthy people would have enormous social value. Even if a SARS-CoV-2 challenge trial only indicates vaccine efficacy for young health populations, this would still have enormous social value by contributing to herd immunity given that young people disproportionately spread the virus to older and immunocompromised people. Also, because of the need to produce billions of doses and the limited production capacity that exists, multiple vaccines will likely be needed, in which case a vaccine for young healthy people can ensure a sufficient supply of approved vaccines for other demographics.

Limitations of Timeline

In order to conduct a challenge trial, researchers must manufacture a dose of the coronavirus in a biocontained facility, and a trial protocol must receive ethical approval. Phase III trials are already underway, and by the time challenge trials are feasible, we will likely have early data on the efficacy of Phase I vaccines like Oxford or Moderna. Therefore, challenge trials will not actually help accelerate the current vaccine development timeline.
  1. We need more vaccines. Amnesty International recently found that since rich countries have pre-purchased most of the limited supply of COVID-19 vaccines, 9 out of 10 people in poor countries won’t get vaccinated in 2021. Many leading vaccine candidates are difficult to distribute in the developing world, leaving as many as 3 billion people without accessWe will need more vaccines, and especially if transmission declines due to the first batch of available vaccines, challenge trials can help us get there.
  1. Challenge trials have broad scientific value. Challenge trials can also play a complementary role to Phase III trials by more quickly and precisely determining correlates of protection, the extent to which antibodies confer immunity, and early stage COVID-19 pathogenesis. The ability to observe participants closely and gather samples while tracing the progress of infection in real time, knowing exactly when they were infected and with what dose, and being able to follow up over a long period, would offer an unprecedented level of scientific and medical insight into an unfamiliar virus.
  • How” — 1Day Sooner

Risking Trust in Science

Data gathered from a COVID-19 human challenge trial would have such limited applicability to vaccine and treatment development that the benefits of such a trial would not outweigh the risk. Since a challenge trial would include only young and healthy trial participants, the resulting data would not necessarily be generalizable to older immunocompromised people– the exact demographic that is bearing the brunt of this pandemic.

  1. A death in a challenge trial is very unlikely. The short-term risk of death from COVID-19 for young healthy people with access to excellent healthcare is so low that it is difficult to measure.
  1. Public engagement can address this concern. As Caplan, Eyal, and Plotkin point out, “Some have speculated that challenge trials would destroy public trust in SARS-CoV-2 vaccines, but there is no basis for this speculation. The only empirical data we could find on the public’s opinion of challenge trials are from a deliberative workshop in the UK and a survey of 5,920 participants in the UK and seven other countries. Both suggest public enthusiasm for challenge trials.”  What is more, with sufficient educational outreach, people will know a) that challenge trials are risky and could involve death, and b) that any challenge trial death would be from COVID-19, not a vaccine. This will make a death or serious illness in a challenge trial less jarring. This public engagement is a precondition for challenge trials and we at 1Day Sooner hope to play an instrumental role in educating the public about these studies.
  1. Challenge trials could fill knowledge gaps, aiding clear public health communication. Data gleaned from challenge trials can actually help fight vaccine misinformation by quickly offering precise data about vaccine efficacy, early development of COVID-19, the extent to which antibodies confer immunity. Filling these knowledge gaps will strengthen the ability of regulators to make clear and prudent public health decisions.

Concerns about Diversity

In order to conduct a challenge trial, researchers must manufacture a dose of the coronavirus in a biocontained facility, and a trial protocol must receive ethical approval. Phase III trials are already underway, and by the time challenge trials are feasible, we will likely have early data on the efficacy of Phase I vaccines like Oxford or Moderna. Therefore, challenge trials will not actually help accelerate the current vaccine development timeline.
  1. There is crucial work to be done. People of color, and Black people in particular, have been historically neglected, oppressed, and exploited in human subjects research. It is utterly critical that any human challenge trial commits to anti-racist practices, such as engaging with scientists and doctors of color in the design of a trial and having informed consent protocols that are informed by the literature on how communication practices can have varying results for different racial groups. We further our work on racial equity, we have hosted several roundtables on race and vaccination in healthcare and vaccine trials. You can view the roundtables on our YouTube channel.
  1. Informed consent is paramount, and 1Day Sooner is working to include volunteer voices in challenge trial design. A through-line in previously unethical and racist human subjects research was a lack of informed consent: participants did not voluntarily enter the trial with an understanding of the risks they would incur, many of which were uncertain. 1Day Sooner’s fundamental goal is to advocate on behalf of potential challenge trial volunteers, and the paramount consideration therein is ensuring that the rights, dignity, and agency of volunteers are respected in a challenge trial.
  1. Challenge trials involve fewer trial participants, making trial diversity more feasible. Since exposure to the virus is guaranteed in a human challenge trial, researchers can conduct a trial with just a few dozen participants. This means that recruiting a racially representative trial may be more feasible than in Phase III trials, which involve tens of thousands of trial participants.