The Home Run Approach

Season 1: Episode 37
May 19, 2020

Photo via Centers for Disease Control and Prevention

The idea of intentionally infecting volunteers to speed up development of a COVID-19 vaccine has piqued a lot of interest. But that’s not the only way human challenge trials could be used.

Listen to the full episode below, read the transcript or scroll down for more information.

Click here for more of our coronavirus coverage.

The Basics: Human Challenge Trials

Human challenge trials — where healthy, consenting, adult subjects are given a vaccine and then infected or “challenged” with a live virus — date back to 1796 and the smallpox vaccine. That experiment — where physician Edward Jenner injected his gardener’s 8-year-old son with a vaccine and then exposed him to smallpox — as well as many others over the last two centuries would not pass modern ethical standards.

Over the last few decades, however, ethical oversight and scrutiny of human challenge trials has increased significantly. Researchers usually spend at least a year identifying the proper dosage and developing a study model that must be approved by an independent review board and the FDA.

More than 120 challenge trial studies were published in the last decade, with some playing an important role in new vaccines being approved. They are generally only considered an option for diseases with known treatments or which scientists know a lot about such as malaria, dengue, cholera and influenza.

The Latest: Challenge Trials and COVID-19

Even though relatively little is currently known about COVID-19, including how to effectively treat it, a growing number of scientists and policymakers think challenge trials could be a viable option to speed up development of a vaccine.

One proposal argues that scientists could save 3 to 6 months if they replaced the final step before the FDA approves a vaccine — where researchers prove the vaccine actually works — with a challenge trial. This would come after initial safety testing and be paired with an additional safety trial.

This idea has spurred more than 20,000 people around the world to volunteer for such a trial through the online advocacy group 1Day Sooner, and prompted studies of the idea by the World Health Organization and the National Institutes of Health.

The Tradeoffs: Different Uses of Challenge Trials

While using challenge trials to speed up vaccine development has captured the imagination of many in the scientific, policymaking and lay communities, it is far from universally endorsed. 

Concerns include the risks of infecting people with a virus scientists know so little about, whether the results would be generalizable to the broader population and whether participants fully understand the risks. (Even those currently opposed to challenge trials say it’s worth preparing for them now since that process will likely take 6 to 12 months and much could change that alters the tradeoffs of a challenge trial, such as a failed vaccine candidate and/or the discovery of a successful treatment.)

It is also not the only, or even the most likely, use of human challenge trials for COVID-19, according to experts.

Replace

The Idea: Replace a traditional Phase III efficacy trial with a challenge trial to prove a vaccine works.

Pros:

  • Would only require a few dozen study participants as opposed to thousands.
  • Would not have to wait for participants to be exposed in the course of their normal lives, which can take years.
  • Could speed up emergency use authorization of vaccine by 3 to 6 months, according to supporters.

Cons: 

  • FDA rarely approves vaccines without data from a large field trial.
  • Would require infecting people with deadly virus without proven treatment.
  • May not meaningfully speed up process with some traditional field trials expected to start this summer.

Prioritize

The Idea: Use challenge trials to identify the most promising vaccine candidates to advance to field trials.

Pros:

  • Could limit the number of time-consuming field trials required to identify effective vaccine.
  • Would still allow regulators access to data from large field trials before approving vaccine.

Cons: 

  • Still requires exposing volunteers to virus without known treatment.
  • Might not save as much time as replacing field trials.
  • Requires broad cooperation among vaccine producers.

Immunity

The Idea: Infect people recovered from COVID-19 to learn more about how immunity to COVID-19 works.

Pros: 

  • Identifying what makes people immune could make it easier to get people back to regular life and develop vaccines.
  • Would involve volunteers who have already recovered from COVID-19 and should be at lower risk for serious illness.
  • Would not disrupt the normal vaccine development process.

Cons: 

  • Would not as directly speed up vaccine development process.
  • Still requires exposing volunteers to virus without known treatment.
  • Lower perceived benefit may make it more difficult to recruit volunteers.

Transmission

The Idea: Test how COVID-19 passes by infecting one person and pairing them with a non-infected person.

Pros: 

  • Studying early and asymptomatic transmission is very difficult.
  • Better understanding how the virus spreads could allow more targeted public health efforts and easing of broad-based restrictions.
  • Would not disrupt normal vaccine development process.

Cons: 

  • Would not directly enhance vaccine development process.
  • Still requires exposing volunteers to virus without known treatment.
  • Lower perceived benefit may make it more difficult to recruit volunteers.

Episode Resources

Select Research and Coverage of Human Challenge Trials:

Ethics of controlled human infection to study COVID-19 (Seema Shah et. al, Science, 5/7/2020)

Infect volunteers with Covid-19 in the name of research? A proposal lays bare a minefield of issues (Helen Branswell, STAT, 5/1/2020)

Key criteria for the ethical acceptability of COVID-19 human challenge studies (World Health Organization, 5/6/2020)

A strategic approach to COVID-19 vaccine R&D (Lawrence Corey, John Mascola, Anthony Fauci and Francis Collins; Science; 5/11/2020)

Studies that intentionally infect people with disease-causing bugs are on the rise (Jon Cohen, Science, 5/18/2016)

Support for Human Challenge Trials for COVID-19

1Day Sooner

Human Challenge Studies to Accelerate Coronavirus Vaccine Licensure (Nir Eyal, Marc Lipsitch and Peter Smith; Journal of Infectious Diseases; 3/31/2020)

Extraordinary diseases require extraordinary solutions (Stanley Plotkin and Arthur Caplan, Vaccine, 4/20/2020)

Episode Credits

Guests:

Lehua Gray, Challenge Trial Volunteer

Seema Shah, JD, Associate Director of Research Ethics, Lurie Children’s Hospital

Zeb Jamrozik, MD, PhD, Monash Bioethics Centre

Anna Durbin, MD, Professor of International Health, Johns Hopkins Bloomberg School of Public Health 

Music composed by Ty Citerman, with additional music from Blue Dot Sessions.

Additional thanks to:

Tom Darton, Josh Morrison, Pieter Neels, Peter Smith, the Tradeoffs Advisory Board…

…and our stellar staff!