The results of a recent study indicate potential research participants are open to alternative vaccine trial designs, including challenge trials in which participants are exposed to COVID-19.1

Researchers started the study in May 2020 as coronavirus vaccines development began. They wanted to see what people thought about accelerated clinical trial vaccine designs.

“Where we started was recognizing that early after vaccines, before trials were run, folks talked about ways to facilitate vaccine development,” says Joshua Kalla, PhD, assistant professor of political science and assistant professor of statistics and data science at Yale University.

For instance, one type of accelerated trial design would expose participants to the virus after they were given the study vaccine. The goal would be to see if the vaccine was effective at preventing them from contracting COVID-19.

“There were lots of people pushing for human challenge trials, and there was pushback on the scientific validity and ethics of these accelerated designs,” Kalla says. “We were interested in what the public thinks about these types of accelerated designs and whether the public thinks they’re ethical. Public opinion matters.”

One of the important functions of IRBs is to determine societal attitudes, which play an important role in determining what is ethical. “The World Health Organization came out with a document on accessibility of COVID-19 studies, and they stated challenge research programs should be informed by consultation and engagement with the public,” he explains.

The researchers spoke with IRB members and decided to seek a broader population to learn about their thoughts on the ethics of vaccine trials. “What we did was run a large online survey across a number of different English-speaking countries,” Kalla says. “We presented people with two fictional trial designs: One was closer to the standard vaccine trial, which ended up being what most pharmaceutical companies went with — the status quo approach — and the other was accelerated design.”

The status quo approach was described as recruiting 9,000 healthy volunteers, administering the vaccine to 4,500 and the placebo to the other 4,500. The human challenge design was to recruit 80 healthy volunteers ages 18-30 years and give 40 people the vaccine and 40 people the placebo.1

“We did tell participants that 40 people in the placebo group would be exposed to the virus, and all participants were young people, so it was unlikely there would be serious complications and very unlikely that any would die from the virus,” Kalla explains.

Researchers described it as a controlled setting in a medical research center where people would receive healthcare while participating in the clinical trial. “The key difference is the standard trial design tends to have a larger sample size and takes longer, but they’re not impacting people with COVID-19,” Kalla says. “With the other design, researchers are intentionally exposing people to COVID-19, and we ask people which of these two trials they prefer.”

Most of the study’s participants preferred the accelerated design and thought it was ethical. “We found, overall, people preferred the challenge trial to the standard trial design. This was true across countries and among older people, people of color, and people who lived in higher COVID-19 case areas,” Kalla notes. “We asked how ethical they thought the challenge to be — 75% said it was ethical and 6% said it was not ethical.”

While conducting the study, investigators did not know how much faster a challenge trial might be from the traditional design. They changed the examples to reflect different timelines. For instance, one case predicted the challenge trial would produce a vaccine by November 2020 and the traditional trial by May 2021, a six-month difference.

“Often in a standard design, more people tend to get sick with COVID-19 than in the human challenge trial design. [This is] because the standard design has a larger sample size,” Kalla says. “There would be a larger pool of people who are going about their lives as usual.”

The researchers’ study case predicted half as many people would die from COVID-19 with use of the accelerated design — 1.2 million vs. 2.4 million — because the accelerated design would produce a vaccine six months sooner.

As it turned out, there was an early push for some pharmaceutical companies to conduct a challenge trial, but none had done that, Kalla notes. The first human challenge trial was launched in the United Kingdom well into the pandemic.2

“We didn’t know what to expect,” Kalla says. “I think it’s very interesting that people are OK with having volunteers sign up for a human challenge trial.”

Study participants were told everyone who participated volunteered and understood the risks. “It seems like the average person surveyed in the United States and in much of the English-speaking world is OK with people being sick and having to participate in these trials if they can get out of the pandemic faster,” Kalla notes.

The study’s findings suggest IRBs might want to think outside the box about accelerated design of clinical trials and not assume that these are ethically unacceptable to the public.

“IRBs may want to think beyond the single community member on its board and think about using tools like surveys to get a broader sense of what a community person thinks about a study,” Kalla says. “There may be biases if we limit it to the point of view of a single IRB member because they are not representative of the mass public.”

REFERENCES

  1. Broockman D, Kalla J, Guerrero A, et al. Broad cross-national public support for accelerated COVID-19 vaccine trial designs. Vaccine 2021;39:309-316.
  2. Gallagher J. COVID-19: World’s first human challenge trials to start in UK. BBC News. Feb. 17, 2021.