A Challenge Trial for COVID-19 Would Not Be the First of Its Kind
As the 2009 pandemic flu virus infected millions around the world, Matthew Memoli began planning to expose healthy volunteers to the pathogen—a proposal that met with considerable opposition. The scientific community was divided on whether the approach was ethical or even warranted.
As the director of the Clinical Studies Unit at the Laboratory of Infectious Diseases at the National Institute of Allergy and Infectious Diseases (NIAID), Memoli recognized the value of a so-called challenge trial for flu, and there was precedent for conducting one. “Our current vaccine and most of the antivirals that we use for flu were all developed in some part because of challenge studies,” says Memoli. But at the time he was applying for regulatory approval in 2010, it had been a decade since anyone had done a flu challenge study.
He made his case for reviving the approach to address the ongoing pandemic virus. He argued to numerous groups that a controlled exposure that mimicked what people could encounter in the real world would allow researchers to track subjects’ immune responses and test drugs and vaccines efficiently and with far fewer people than would be needed for traditional clinic trials. In the end, the US Food and Drug Administration (FDA) and the National Institutes of Health (NIH) ethics review board agreed with him, and he developed a challenge model using a wildtype strain of H1N1 that has since been sprayed up the noses of more than 400 volunteers.
While I’m a proponent of challenge models, I think there are some ethical requirements and those include having a significant knowledge of the long-term effects of the infection.—Monica McArthur, University of Maryland School of Medicine
“I personally take this very seriously. I’m making people sick on purpose. It’s not a joke; it’s a very serious thing that I’m doing. And I only want to be doing it if it really is truly something that is beneficial,” Memoli says.
Ten years later, Memoli is once again working on developing a human challenge model for a pandemic virus—this time, SARS-CoV-2. It’s not yet clear whether it will be used to test out vaccines or even therapeutics for COVID-19, he says, but “I have always believed that we should be preparing to do it.”
Since the early days of the COVID-19 pandemic, a debate has focused on whether a challenge study for COVID-19 vaccines should proceed. In June, an advisory group to the World Health Organization (WHO) issued a report providing guidelines for how such trials could be designed, but the committee was undecided over whether they could ethically proceed. Late last month, the Financial Times reported that the UK government announced it was considering a vaccine challenge trial for COVID-19 that could start early next year. (Imperial College London and the contract research organization hVivo, reportedly partnering on the trial, did not respond to requests for comment before deadline.)
For many pathogens other than SARS-CoV-2, challenge studies have already become a key part of research on vaccines and therapeutics. Besides influenza, scientists have developed challenge models for an array of other viruses as well as bacteria and parasites. “I think challenge studies have become more accepted, honestly,” says Memoli. “Since I started doing the flu challenge, I think there was a big resurgence.”