03:46 - Source: CNN
Hear from first US participant to receive Moderna Phase 3 trial vaccine

Editor’s Note: Robert Klitzman is a professor of psychiatry and director of the masters in bioethics program at Columbia University. He is author of “Designing Babies: How Technology is Changing the Ways We Create Children.” The opinions expressed in this commentary are solely those of the author. View more opinion articles on CNN.

CNN  — 

As scientists race to develop a Covid-19 vaccine, thousands of people have expressed their interest in participating in clinical trials that would expose them to the virus. Many of these people are eager to help in the name of saving lives and willing to take on any potential risks.

But should they be so eager to participate?

Usually, vaccines are developed over the course of several stages, starting with testing in petri dishes and animals. The small fraction of these that show some promise then enter several phases of human trials, where researchers administer the vaccine to an increasing number of people while monitoring the dosage and assessing side effects and efficacy.

In Phase 3 (the last phase before FDA approval), researchers separate the participants into two groups, and administer the vaccine to one group while giving the other a placebo.

Researchers typically wait several months as the participants lead their lives, going to work, seeing family members or taking public transportation. If fewer people who received the vaccine than those given the placebo end up getting infected, it is deemed effective.

Robert Klitzman

Because doctors have an ethical duty to minimize harm, they generally avoid purposely infecting people with a virus. But the usual process of waiting to see how many of the participants are naturally infected takes a long time.

And if the trials are being conducted in a place where community spread is low, participants in both groups may never be exposed to the virus, and researchers would have a hard time determining whether the vaccine works.

Given the urgency of finding a safe and effective Covid vaccine, researchers are, in some cases, skipping animal testing. So-called “human challenge” or “controlled infection” trials have also been proposed, which would allow researchers to intentionally expose all participants to the virus to assess the experimental vaccine’s effect more quickly.

An organization called 1Day Sooner, which advocates for the use of “human challenge” trials in the development of a Covid-19 vaccine, asks people (especially those who are young and have no underlying health conditions) to enter their names online and state that they are willing to volunteer to take part in such a trial.

The idea has garnered considerable support, with more than 32,000 people expressing interest, according to the 1Day Sooner website. The group also organized an open letter addressed to National Institutes of Health Director Dr. Francis Collins, highlighting the importance of controlled infection trials. More than 150 people have signed it, including 15 Nobel Laureates and a number of other experts and academics.

On paper, this approach seems straightforward and full of potential, given that the world is desperate to develop a Covid-19 vaccine. But it is critical that the process – along with the final product – is as safe as possible, especially given the mistrust of science in this country and the growing anti-vaxxer movement. This novel study design raises several significant problems that have not yet been resolved.

More than 165 Covid-19 vaccines are currently in development. No one knows which one, if any, will work. Vaccines typically take more than a decade to develop; scientists usually test many possibilities to find one that succeeds.

In general, only about 14% of vaccines that enter Phase 1 clinical trials end up getting approved. But that success rate is based only on studies that have published data – many drug companies and researchers fail to release the data when their experimental products don’t work. The actual odds of success are undoubtedly much lower.

If a controlled infection trial of a vaccine fails after all the participants have been infected, some will likely get very sick and die. According to the US Centers for Disease Control and Prevention data from mid-February to mid-March, as many as 20.8% of 20- to 44-year-olds infected with Covid required hospitalization, 4.2% were admitted to the intensive care unit and 0.2% died.

It remains unclear whether controlled infection trials will be implemented, or how. Proponents of these trials say they might need about 100 participants for each study. If researchers took this approach for 20 studies, 2,000 people would be infected with Covid.

Assuming none of the vaccines worked, an estimated 416 of these participants could need hospitalization, 84 could require ICUs and four could die, based on the CDC data from earlier this year. If one out of the 20 trial vaccines works, only 100 participants would be protected, while 1,900 would be infected.

Most vaccine trials are designed to test whether the product leads people to develop antibodies, not whether the vaccine actually prevents infection. Even if an experimental vaccine causes someone to develop antibodies, they might not successfully trigger all the components of the body’s immune system to effectively attack the virus.

To top it off, researchers haven’t determined how long the Covid antibodies will last, how many antibodies will protect people from infection and whether reinfection is possible. While willing volunteers – many of them young adults – may think they face little to no risk in controlled infection trials, some are putting themselves at greater risk than they realize.

A vaccine may also only be partially effective and could cause significant side effects. It might, for instance, create antibodies only in perhaps 50% or 60% of participants, and cause serious illness in 10%.

Given Covid’s enormous devastation, the US Food and Drug Administration has said it will approve a vaccine that prevents disease or decreases its severity in at least 50% of those who receive it.

It’s important to remember that in 1976, a swine flu vaccine was approved and eventually administered to about 45 million Americans, more than 450 of whom developed Guillain-Barre syndrome – a rare neurological disorder in which the body’s immune system mistakenly attacks the nervous system.

The incident has helped fuel the anti-vaxxer movement ever since.

Drug companies developing the vaccine will also undoubtedly look to profit from it. Remdesivir, an antiviral drug that has shown signs of speeding up recovery in moderately ill patients with pneumonia from Covid-19, costs $2,000-$3,000 per person for a five-day treatment course.

While proponents of controlled infection trials argue that participants would be saving millions of lives, that would be the case only if a vaccine proves to be safe and effective – not to mention accessible for millions of people.

Unfortunately, given the ever-rising costs of drugs in the US, pharmaceutical companies that end up developing a successful vaccine may charge a significant amount of money for it.

Though the Trump administration recently arranged a $1.9 billion deal with Pfizer for 100 million doses of a vaccine, with rights to acquire 500 million more, that experimental vaccine is only one of many currently being investigated.

Proponents of challenge studies have also largely ignored the question of whether participants (or their family members) will be compensated if they end up with long-term medical problems or die as a result of the trial.

And while participants are generally paid to participate in conventional vaccine trials, subjects in controlled infection trials would presumably get paid even more, raising concerns that this would attract people who are in financially vulnerable positions to assume higher risks.

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The country faces an economic crisis and there is a long, dark history of researchers experimenting disproportionately on poor people and people of color. Just look at the case of Henrietta Lacks, a Black woman whose cells were taken from a tumor on her cervix without her knowledge and used in medical research for decades without her family’s knowledge.

While we shouldn’t automatically reject the possibility of human challenge trials, given the number of lives that could be saved with an early vaccine, we need to proceed very cautiously.

If we do embark on these trials, researchers should be even more selective about which experimental vaccines to use. Drug companies should also commit to making the vaccine, if it is approved, affordable for millions of people.

Researchers, should they embark on controlled infection trials, should administer the vaccine and infect only a handful of participants at a time, and check whether it’s effective before giving it to additional subjects to minimize any potential damage.

Informed consent and robust guidelines for all participants is crucial, and researchers should quiz each participant to guarantee that he or she fully understands the potential risks.

We all want a safe, effective and widely available vaccine, but researchers need to ensure that participant safety is also thoroughly considered.