/What are human challenge studies?

What are human challenge studies?


Recently, the government of the United Kingdom received ethics approval to run the world’s first SARS-CoV-2 human challenge study. In this article, we explain what human challenge studies are and what insights they can provide.

As it stands, 11 COVID-19 vaccines have been authorized, across several countries. Waiting in the wings are at least 80 vaccine candidates, 20 of which are in phase 3 clinical trials.

It is truly incredible that within 1 year of discovering a new virus, we already have a range of experimental and authorized vaccines, but this is not the end of the story.

There is still room to improve existing vaccines. Additionally, having a range of companies manufacturing vaccines can be beneficial — if problems arise with one supply chain, another can take its place.

It may also be the case that certain vaccines work better in some populations than in others.

To help streamline and improve vaccine testing and discovery, the U.K. government is funding human challenge studies.

The World Health Organization (WHO) describe a human challenge study in the following terms:

“Human challenge trials are trials in which participants are intentionally challenged (whether or not they have been vaccinated) with an infectious disease organism.”

This approach is nothing new, and it has helped medical science progress over centuries. The first true human challenge study was conducted in the 1700s. The experiment helped assess whether variolation — a method of inoculation — could prevent smallpox.

More recently, these types of studies have helped scientists develop vaccines for diseases including cholera, typhoid fever, influenza, and dengue fever.

The study making headlines at the moment, of course, will involve SARS-CoV-2, the virus responsible for COVID-19.

According to a press release from the U.K. government, the U.K. COVID Challenge study will initially include up to 90 volunteers aged 18–30 years.

They explain that participants “will be exposed to [SARS-CoV-2] in a safe and controlled environment to increase understanding of how the virus affects people.”

In the first phases of the research, the scientists will be using “the version of the virus that has been circulating in the U.K. since March 2020,” rather than any of the newer variants.

Of course, in a study like this, safety is paramount. All participants will be monitored by healthcare specialists 24 hours a day. Before the trial begins, the participants will be screened to check that they have not already had a SARS-CoV-2 infection.

Once the researchers introduce the virus into each participant’s nose, the participants will quarantine in a hospital for 14 days. Each will receive around £4,500 (almost $6,300) for their time, which will include follow-up tests over the next 12 months.

In later studies, the scientists plan to test vaccine candidates that have already proved safe in clinical trials. They hope to give these vaccines to small groups of participants, then introduce SARS-CoV-2.

In this way, they can more quickly identify which candidates might be most effective.

The research is being orchestrated by a number of institutions, including the U.K. government’s Vaccines Taskforce, as well as Imperial College London, the Royal Free London National Health Service Foundation Trust, and the clinical company hVIVO, an expert in viral challenge studies.

According to Clive Dix, the interim chair of the Vaccines Taskforce, the human challenge study will “offer unique insights into how the virus works and help us understand which promising vaccines offer the best chance of preventing the infection.”

Although real-world studies are the backbone of medical research, there are some things that they cannot easily tell us. For instance, one of the first things that the upcoming trial will investigate is how much virus is necessary to spark an infection. This would be nearly impossible to discover with real-world research.

Human challenge studies also allow scientists to observe the progression of an infection from the very moment that the virus enters the body.

They can also help scientists work out the details of how someone with a SARS-CoV-2 infection transmits virus particles into the environment.

Additionally, human challenge studies might help us understand which people are most likely to develop symptoms and, just as important, which people are likely to have none.

The chief scientific officer of hVIVO, Dr. Andrew Catchpole, hopes that the studies will also help experts understand “exactly what type of immunological response is required to confer protection from reinfection.”

Some people have questioned whether we truly need human challenge studies now that we have functioning COVID-19 vaccines. The authors of an opinion piece in BMJ explain why these studies are still important:

“While such trials are unlikely to accelerate the development of the first vaccines to hit the market, they may prove essential for second- and third-generation vaccines, which is essential, since rich countries are likely to outbid poorer ones for the first batch of vaccines.”

They continue: “There are over 300 candidate vaccines, and scientists will not be able to conduct conventional large-scale phase 3 studies for all of them. Challenge studies can prioritize the best candidate vaccines to test and prove efficacy in cases where transmission is low.”

It is important to note that not all scientists support the idea of human challenge studies using SARS-CoV-2. In the BMJ opinion piece linked to above, Dr. Charles Weijer, an expert on the ethics of randomized controlled trials argues that the risks are too great.

He explains that although, “Thousands of volunteers have participated in challenge studies in the past 50 years, and none has died as a result,” SARS-CoV-2 is a different case.

He explains that this track record “is because scientists have steadfastly protected volunteers by restricting challenge studies to well-understood diseases that would either resolve on their own and have no long-term harmful effects or to diseases for which curative treatment is available.”

He continues, “What we do know of the risks of SARS-CoV-2 infection suggest that they are too great to be permitted ethically.”

Although the ethical debate is sure to continue, the trial has been reviewed and passed by the country’s research ethics committee. Dr. Stephen Griffin, an associate professor in the Leeds School of Medicine, who is not involved in the study, explains:

“The study has received ethical approval from a dedicated research ethics committee convened by the [Health Research Authority]. […] The protocol contains an exhaustive list of criteria by which volunteers will be included, set out to minimize the risk of serious disease and death in participants.”

The scientists involved in the human challenge trial are now actively looking for participants.

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