In new guidelines issued on May 6, the World Health Organization has said that well-designed human challenge studies could not only accelerate coronavirus ( COVID-19 ) vaccine development but also make it more likely that the vaccines ultimately deployed will be far more effective.
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In human challenge studies, healthy participants are first administered the candidate vaccine and then deliberately exposed to novel coronavirus . In conventional clinical trials, healthy participants are administered the candidate vaccine, and the safety and efficacy of the vaccine is assessed through natural infection.
Compare and select
The guidelines say that it would be “substantially faster” to carry out vaccine field trials through human challenge studies as far fewer participants need to be exposed to candidate vaccines to “provide (preliminary) estimates of efficacy and safety”. It says this approach will make it possible to compare the efficacy of multiple vaccine candidates and select the most promising vaccines for larger studies.
In addition to accelerating vaccine development, human challenge studies can help validate tests for immunity to the virus, identify correlates of immune protection, and investigate the risks of transmission by infected individuals, it says.
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COVID-19 can kill millions (over 3,00,000 people have already died) and strain the healthcare system worldwide. While physical distancing can help to reduce virus spread, it can disproportionately affect the underprivileged groups.
Successes and risks
While human challenge studies are ethically controversial, such studies have been performed safely in tens of thousands of people in the last 50 years and helped accelerate the development of vaccines against typhoid and cholera. Such a study for Zika virus was also conducted.
According to the guidelines, challenge studies would be least risky for young healthy adults aged 18-30 years, as the hospitalisation rates in this age group is about 1% and fatal infection rates around 0.03%. But a March 27 study in the Morbidity and Mortality Weekly Report found that 20.8% of patients aged 20–44 had severe disease which required hospitalisation, and 4.2% of patients developed critical disease, which required admission to an ICU.
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Human challenge studies are to be carried out only in specialised centres where close monitoring and ready access to early supportive treatment for participants, including critical care if required is available, the WHO says.
But what makes such studies for COVID-19 particularly risky and challenging is the fact that pathogenesis of the disease is poorly understood and there is no approved treatment available in case participants develop the disease.
Potential benefits and risks should be assessed, quantified and compared with other feasible study designs, and the expected benefits should be maximised and the risks minimised, the guidelines say. “Given the ethically sensitive nature of SARS-CoV-2 challenge studies, assessment of their potential benefits and risks should be especially rigorous,” it says.
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Meanwhile, the U.S. National Institutes of Health is also preparing the ground for human challenge trials for COVID-19 vaccines. The vaccines working group is preparing the scientific and practical considerations for COVID-19 human challenge trials, the Financial Times reports.
Michael Felberbaum, a spokesman for FDA told WIRED that challenge trials are one of the methods it is considering to speed up COVID-19 vaccine development.
Prof Andrew Pollard, who is leading the trial of the vaccine developed by the team at the University of Oxford’s Jenner Institute told The Guardian that there is “huge interest” in the possibility of challenge trials among those working on coronavirus vaccines. “At the moment, because we don’t have a rescue therapy, we have to approach challenge studies extremely cautiously,” Pollard said.
Ethical framework
“Recognizing the uncertainties, risks from SARS-CoV-2 human challenge studies appear comparable to the risks from some other research and activities similar to research,” says Seema K. Shah, a medical ethicist from North Western University, in a paper in Science authored by her that lays out an ethical framework for conducting such studies. “Given the extraordinary nature of the pandemic, our framework and analysis support laying the groundwork for coronavirus challenge studies.” Dr. Shah is also part of the WHO working group that developed the guidelines.
Meanwhile, NBC News reports that that the multinational testing company SGS and London-based hVIVO are planning human challenge studies. Nearly 20,500 people from 102 countries have already volunteered to participate in such studies.
