A human challenge trial (HCT) is a study that deliberately infects volunteers with a virus after they've been given a vaccine, in order to see if the vaccine is effective. Clinical trials usually allow participants to be exposed to COVID-19 in their day-to-day lives, but HCTs intentionally infect volunteers in order to learn about the virus, immune responses, medications, and treatments.
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Human challenge trials take a group of healthy volunteers and give half of the group a vaccine for a specific illness. The other half get placebo (a fake drug they think is a real vaccine). Researchers then purposely expose the entire group to the real virus in a laboratory at a high enough dosage for them all to become infected. After being exposed to the virus, if the vaccinated group does not become sick, while the placebo group does fall ill, it means the vaccine is effective.
HCTs are different than more traditional vaccine trials, which wait until research subjects are exposed to a virus in their day-to-day lives, outside of the laboratory.
A benefit of a human challenge trial is the speed with which volunteers are exposed to the virus. It means researchers can know quickly whether or not their vaccine is effective.
Human challenge trials are also conducted in settings where researchers can control other factors, including when to expose a group to a virus, who gets to participate in the trial, and how volunteers get exposed. They can also involve a smaller number of participants than other medication studies.
The controlled way that human challenge trials are designed means they don't resemble how people get infected by viruses in the real world, outside of labs.
Human challenge trials are controversial and have caused debates about the ethics of infecting healthy volunteers with a virus that doesn't have a cure and can cause death. Though human challenge trials been used to study medications for illnesses like typhoid, cholera, and malaria, those diseases all had proven medical treatments that could stop disease progression if the vaccine did not work. In the case of COVID-19, few treatment options exist, so the amount of risk involved — even in healthy, young, willing volunteers — is significant.
Trial design and ethical considerations for a U.K. human challenge trial gained approval from U.K. regulators on February 17, 2021, enabling the study to proceed and begin enrolling participants. Scientists hope the study will shed light on how much exposure leads to infection and how immune responses develop over time.
The study is designed for controlled settings in hospital isolation rooms using an original coronavirus variant that has been circulating since March 2020, so there will be additional research needed to better understand how vaccines work in the real world and on newer variants.
Knowing that human challenge trials may be needed, and as treatments and vaccines are developed for COVID-19, the World Health Organization (WHO) issued guidance to scientists, doctors, ethicists, and researchers in May 2020. The WHO document provides an overview of the ethics involved, reviews why the studies are being considered, and lists eight criteria for studies to meet for possible consideration. The criteria are designed to ensure that there is adequate scientific justification, that risks and benefits have been carefully considered, that studies are performed with consultation and coordination among members of the public as well as experts and policy-makers, and that study sites are equipped to conduct research to meet the highest clinical and ethical standards, and to ensure that participants are selected to minimize risk.
Human challenge trials take many months to plan and, in the setting of a global pandemic, many experts argue that there is no time to waste in planning for these trials to begin. In an open letter to the U.S. National Institutes of Health, 15 Nobel Laureates and over 100 top scientists and researchers encouraged preparation for human challenge trials for COVID-19 vaccines. The letter was organized by an advocacy group that has collected human challenge trial volunteer signatures from more than 30,000 people in over 140 countries.