Green plants, cool tones, casually placed scatter cushions: this living room in East Melbourne could belong to – or at least, be rented by – any millennial. The squeaky corridor floors are a giveaway, though; along with the beds on wheels.
This isn’t a real estate opportunity, but Doherty Clinical Trials (DCT) – Australia’s first unit dedicated to human challenge studies, where trial participants are given a dose of an infectious disease in a controlled setting. An offshoot of the Peter Doherty Institute for Infection and Immunity at the University of Melbourne, it opens on Monday – a breeding ground, its proprietors hope, for discoveries that may redefine the future of disease.
Human challenge trials, or controlled human infection model (Chim) studies, are “highly valued as one of the most efficient ways to evaluate the efficacy of novel vaccines and therapeutics”, Andrew Brockway, the facility’s CEO, says. They serve two primary purposes: providing insight into diseases, such as flu or malaria, or “to more quickly determine if and how well a specific vaccine or drug in development works” by administering it to a small cohort, all of whom are subject to the same conditions.
According to Brockway, this can produce more reliable and reproducible results than larger studies, where variables are less controlled, and can help explain what types of immunity affects the disease by comparing how different participants react to the same infection. Trials of this kind can shave years off the usual decade it takes for a vaccine to get approved. Speeding up this process can also have major financial benefits.
Challenge trials, which began more than a century ago and have been spearheaded by the UK, Australia, Europe and the US, are costly to carry out and recruiting healthy volunteers can be difficult.
That has done little to dim the aspirations of DCT, which plans to move to a larger site in 2027. On the slate in its current home are studies where participants will be infected with influenza, malaria, strep A and oral gonorrhoea. Other trials, run in collaboration with academic researchers and biotech companies, will test novel technologies, including a microneedle patch and a prophylactic nasal spray for Covid – both of which are designed to replace jabs altogether – while a Moderna tie-up will seek to develop mRNA vaccines. Brockway hopes the data amassed here will “potentially contribute to the management of future pandemics” too.
Meta Roestenberg, a professor in vaccinology and the clinical head of the Controlled Human Infection Center at Leiden University in the Netherlands (not associated with the Doherty clinic), says human challenge trials have yielded “very fundamental insights that are extremely useful” when it comes to infectious disease research. She points to the development of Vaxchora, the first cholera jab to be approved in the US in 2017, and RTS,S, a malaria vaccine now being rolled out in sub-Saharan Africa as among those that “show very clearly how challenge studies can help the development of novel products”.
But who would sign up? Brockway says participants are “often young university students”. “You get a lot of backpackers come through,” he says, likely encouraged by the financial reward, which is set at the minimum wage of $23.23 for each hour spent at the clinic, which can run to weeks, staying at the facility in some cases. “It’s not that we can just go and say, ‘Hey, are you coming for malaria? We’ll give you $2,000 for this visit’,” Brockway says. Payment is a standard hourly rate, not based on the disease.
In between observations and blood tests, participants can peruse the neatly curated bookshelf or visit the game room, stream films or do Zoom calls. The idea is to make it appealing – extra-wide beds, nice linen – in order to encourage participants to come back or tell their friends. As short-term rentals go, it’s not too bad.
Some volunteers are in it for the science. Keller Scholl, a 29-year-old PhD student, enrolled in a Zika challenge trial last year in the US after seeing a tweet calling for participants: “I want to make the world a better place. This was something I could do and we don’t have enough volunteers,” he says of his decision to sign up. Although he adds that he “wouldn’t have been able to do it without the pay”, which amounted to about $7,500 for nine days.
Scholl and three other participants were set up in a hospital facility. They had a five-bed dorm to themselves and shared book recommendations, ordered in food (although one volunteer did “great scrambled eggs”) and watched Netflix. The days passed easily enough until a rash developed on Scholl’s forehead and upper arms. On day nine on the journey home, fatigue set in “and the itch became painful and kept escalating”. It turned out to be “nothing too serious”, he says, admitting that he would have preferred to be in the placebo group, receiving a dose of saline instead of Zika.
Even so, he would “absolutely” do it again – a sentiment shared by 22-year-old Jenny McMichael, who recently completed a whooping cough challenge trial in the UK and is now looking for another in which to participate. “People assume you’re crazy for doing it,” she says. “[But] I actually found it to be really fun.”
Volunteers are crucial to challenge trials’ future, but Roestenberg appreciates that the notion of “deliberately inducing symptoms in healthy volunteers, giving people disease – this is very counterintuitive when you think about the ‘first, do no harm’ principle of medicine” – the promise made by all doctors when taking the Hippocratic oath.
There are other issues at play. Along with the fact that being infected with well-known diseases “puts people off” (again, counterintuitively, more so than experimental drug trials), they also give rise to major ethical concerns. I ask Scholl if he felt he wholly understood the ethical implications. “I was a philosophy minor: I’m not confident in the ethical implications of anything,” he says.
Challenge studies require approval by an independent ethics committee that has prior experience in reviewing such trials and are bound by the guidelines set by Australia’s National Health and Medical Research Council. Trial subjects must sign a consent form – outlining all benefits and risks and how to seek compensation – which is also reviewed by the ethics committee before the trial’s start. Medicines Australia is the custodian of the voluntary compensation guidelines, which stipulate that trial sponsors must pay compensation to participants in the case of injury.
Brockway says DCT, like all facilities that do challenge trials, will “operate under the highest standards of scientific, clinical and ethical conduct”.
Patrick Foong, a senior law lecturer specialising in bioethics at Western Sydney University, says “there is a risk-benefit analysis that has to be justified” for human challenge trials. “The human participants in research may not actually know what they’re getting themselves into.” That so much trial recruitment now takes place on social media, seemingly promising thousands of dollars in return for a few scratches of a needle, “is where we get a little bit concerned”, Foong adds. “If people are desperate, they are not really in the right frame of mind to be able to make an informed decision.”
This issue was brought into sharp focus during the pandemic, when challenge trials for Covid vaccines were floated. Concerns were raised that “many people would have lost their jobs, leading to financial desperation and the possible attraction of vulnerable participants”, Foong wrote in a co-authored article at the time. “The serious concern is that the money offered to them may operate as an inducement/undue influence to participate in the experiment, which may raise further ethical concerns.”
The benefits were ultimately deemed to outweigh the risks, and the trials went ahead (another Covid challenge trial was announced earlier this month). Contrary to how things appeared then, DCT’s opening is a signal, Roestenberg thinks, that there is now a greater understanding of the value of human challenge trials.
“I think it makes complete sense that there are more institutes around the world that develop the capacity to actually do these types of studies and make sure that we don’t run into a capacity problem,” she says. “I’m very happy to see that [they are] expanding.”
