The world’s first challenge trial for a SARS-CoV-2 (Covid-19) vaccine is set to begin in 2021—an unprecedented step in clinical research. Although challenge trials are not new, this is the first time regulators are being asked to give the go-ahead for healthy volunteers to intentionally be infected with a pathogen that has claimed more than 1 million lives globally, with no curative treatment available. The stakes could not be higher for volunteers taking part, or for the teams running the studies.
What is a challenge trial?
In a challenge trial, volunteers are intentionally injected with an infectious disease organism in order to test the efficacy of a potential treatment for that disease in real time. While it’s a concept that has been used over hundreds of years to test and improve vaccines we use today, such as cholera, many of the historical examples are considered wholly unethical by today’s standards.
Why is a challenge trial needed for COVID-19?
On average, it takes 4-5 years to develop a new vaccine, and the process involves phase 3 trials involving tens of thousands of people. This timeframe simply isn't acceptable in the case of Covid-19, considering the immediate global threat it poses. That's why researchers have been speeding up the vaccine R&D process by running efficacy and safety studies in parallel. Now they are looking to accelerate the process further by giving volunteers experimental vaccines and challenging them with Covid-19.
It has been argued that “by replacing conventional phase 3 testing of vaccine candidates, such trials may subtract many months from the licensure process, making efficacious vaccines available more quickly.” This, in turn, would reduce the global burden of Covid-19-related death and disability and begin to reverse the effects we’re seeing on the world’s broader health, social, and economic welfare.
What will happen in the challenge trial?
The first Covid-19 challenge trial will take place in the UK. It involves two stages: a characterisation study, which aims to determine the smallest amount of virus needed for a person to develop Covid-19; and the challenge study itself, in which a small group of volunteers will receive experimental vaccines or a placebo, followed by an infection-causing dose of SARS-CoV-2.
Although the study will only involve young and healthy participants at low risk of death from Covid-19, taking part will not be easy for participants. In the past, participants have become very ill during challenge trials, even during trials involving diseases for which cures are available, such as malaria and cholera.
Proponents argue that the net risk to participants “could be acceptable if participants comprise healthy young adults,” as long as they undergo frequent monitoring and are offered the best possible medical care following any infection.
What are the unique requirements of challenge trials?
According to the World Health Organization (WHO) in guidance published before the Covid-19 pandemic, there are "unique and important operational aspects to the conduct of a human challenge trial," in addition to the obvious ones, such as viral containment. Challenge trials should be undertaken:
- within an ethical framework in which truly informed consent is given
- with abundant forethought, caution, and oversight
- in line with expectations of a vaccine study—i.e. clear compliance with GCP
- in accordance with a protocol
- in clinical facilities capable of providing continuous monitoring and medical attention at appropriate timepoints
This presents unique hurdles for the study teams and sponsors to overcome. Putting the appropriate tools in place now to support planning and oversight will be essential.
Take informed consent, for example: In no other context do we ask healthy individuals to accept such risk with little potential of gaining any benefit. The need for consistent and clear communication to participants from the study team is paramount. Thirty-page documents alone will not suffice; study teams need interactive communication tools that can take participants through the trial information at the right pace, ensuring and confirming understanding at every stage.
The success of challenge trials depends on these selfless volunteers who are willing take risks for the broader benefit to society. They deserve the best and safest clinical trial experience possible.