Insights: Pandemic Threat May Open Doors for Human Challenge Trials

Alyssa GovindanNewsletter

Along with the impacts of climate change and increased globalization comes an increase in infectious diseases. Warmer temperatures allow for easier transmission of vector-borne diseases (VBDs) which means that regions that are typically cooler are now getting warmer, allowing for carriers of diseases to thrive. In fact, if global temperatures rise even two to three degrees Celsius, the population at risk for malaria is expected to rise by three to five percent. Other diseases carried by mosquitos are also showing up in unexpected areas.  The Asian tiger mosquito has recently been responsible for Chikungunya in Europe. A Lancet article also charts the rapid trajectory of the West Nile virus, which was first discovered in East Africa but later spread to the United States, then to Argentina, Canada, Romania and Russia.

In preparing for an increase in VBDs and for pandemics in general, global health experts recommend investments in vaccine development and anti-vector agents. One method of testing plausible vaccines is through human challenge trials. Human challenge trials are when participants are injected with an infectious disease in order to test a vaccine’s effectiveness in preventing illness. These types of trials are gaining traction due to the looming severity of infectious diseases and the potential of traditional vaccine testing failing in the future.

Human challenge trials are not exactly new. They have been used since 1796, when Edward Jenner infected people with cowpox – eventually paving the way for the development of the smallpox vaccine.  In recent decades, human challenge trails have been used to test vaccines for illnesses that can be quickly and completely treated.  Results from this method have even been used in applications to the FDA for vaccine licensing.

A recent New York Times supplement sponsored by the Bill & Melinda Gates Foundation delves into the steps that must be taken to prepare for a pandemic, whether it be influenza, a mutation of a common disease or a disease we’ve yet to encounter. Since disease transmission can move fast, regulatory policies may need to be altered.

“We have to look at the regulatory pathway for drugs and vaccines and work out ways to streamline those so they are as efficient as possible without putting patients at risk” said Jeremy Farrar of Wellcome Trust.

There is of course controversy over the ethics surrounding human challenge trials but with appropriate precautions and regulation, many agencies, such as the EMA and FDA are open to discussions with companies aiming to conduct the trials.

The inherent theme in medicine to do no harm is what puts some bioethicists on edge. Although human challenge trials tend to explore illnesses known to be easily treatable, some participants will undeniably experience adverse symptoms.  Others argue that asking someone to put themselves in harm’s way, even for the benefit of others is unethical.

Protecting vulnerable populations is another concern for many bioethicists. Since there have been challenge studies conducted on vulnerable populations without adequate review in the past, it is important to determine a clear ethical framework moving forward.

Since analyses pertaining to the ethics of human trials have habitually focused on diseases that would likely cause no lasting adverse effects, there is little guidance for researchers wanting to branch out to uncertain territory, such as Zika. The National Institutes of Health are planning to fund a trial where participants are inoculated with potential vaccines then given small doses of the Zika virus. In response to this proposed trial, a panel of bioethicists has called for an ethics review of the study design, noting that the risks would not be justified.

Recently, many were shocked by a human trial that took place in England where volunteers swallowed live typhoid bacteria in order to test an experimental vaccine. The vaccine being tested, Typbar TCV, is already being manufactured and used in India, but the manufacturers were seeking pre-qualification from the World Health Organization (which has since occurred). One hundred healthy participants swallowed live Salmonella typhi after receiving either the vaccine or a placebo. Since Typhoid is easily treatable with antibiotics, those that did fall ill were quickly treated. The vaccine proved to be 87 percent effective in preventing typhoid and GAVI has already earmarked $85 million for the procurement of doses next year.

Global health experts and scientists fear that although we don’t know the nature of the next pandemic, they are certain it will occur. The Ebola outbreak that occurred in West Africa just a few years back revealed that the world was unprepared for such an event. Today, pandemic preparedness is on the radar in a way it has never been . Nevertheless, it remains to be seen whether or not the necessary resources and policies will be in place to avert the next .

Alyssa GovindanInsights: Pandemic Threat May Open Doors for Human Challenge Trials