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The Challenge Trial Challenge

Drs. Idowu Aimola and Francis Collins, the later of whom remains skeptical of human challenge trials, looking at a computer imaging program.
NIH director Dr. Francis Collins, left, with Dr. Idowu Aimola. Photo courtesy the National Institutes of Health.

In a world desperate for a safe and effective vaccine against COVID-19, the idea of deliberately exposing healthy young adult volunteers to the novel coronavirus to speed vaccine testing almost seems like a no-brainer.

The world, however, is a complicated place, and brains are quite helpful in navigating it. The medical establishment – informed by generations of experience with human experimentation, some of it quite painful – has so far resisted the urge to try to shortcut clinical trials. In standard trials, a large numbers of subjects go about their daily lives after vaccination. Researchers must wait for a statistically significant number of those who received the vaccine or a placebo to show the results. While vaccine developers are speeding up where they can, such as ramping up manufacturing before a potential vaccine is approved, they are still committed to the same process any vaccine would undergo outside a pandemic.

I think this institutional bias toward the tried-and-true is a mistake in the current situation. However, reasonable people can – and do – disagree about this. Those who object to so-called “human challenge trials” raise legitimate points that deserve consideration.

In challenge trials, volunteers receive a trial vaccine, wait for it to produce the hoped-for immune response in their bodies, and then allow researchers to deliberately infect them – in this case with the novel coronavirus – to see whether and to what extent the vaccine actually protects them. There is no shortage of individuals willing to participate. At the start of this week, the organization 1Day Sooner said it had registered more than 35,000 potential volunteers from 160 countries.

But while there are at least seven vaccines around the world that are currently in phase 3 trials to determine their effectiveness (some of which are combined with phase 2 trials meant to test safety and dosages), none have been publicly identified as challenge trials. This list does not include the only approved COVID-19 vaccine, a recent Russian entry whose testing protocols were abbreviated and opaque. It has drawn near-universal skepticism outside Russia.

COVID-19 seems almost tailor-made for challenge testing because of its idiosyncrasies. While often devastating and all-too-frequently fatal to older victims, evidence so far suggests the great majority of otherwise healthy young adults who contract it either are asymptomatic or experience mild symptoms that clear within a couple of weeks. Limiting challenge tests to people under, say, age 30 with no preexisting conditions should allow most such subjects to get through the test without much difficulty, even if the vaccine doesn’t protect them.

But a great majority is not the same as everyone. In a large enough sample, a certain number of test subjects are likely to experience much more severe illness than expected. Some could even die. Even for those who recover in the way young adults usually do, the potential long-term effects of COVID-19 are still unknowable, since the disease has not yet existed in humans for even a single year.

Skeptics of challenge testing point to these risks, among other concerns. Given how much we don’t know, some have argued that truly informed consent from volunteers is currently impossible. They note the limited range and efficacies of therapies to treat test subjects who go on to develop full-blown COVID-19. They observe that many vaccines, even those considered successful, may only prevent 70% to 80% of infections, or sometimes even less. A fraction of volunteers could be infected even if the vaccine works as designed.

Nor are the risks only to participants. A young volunteer who becomes infected may go on to infect other individuals, including those in vulnerable groups, who never meant to become part of a vaccine trial. And the foreseeable illnesses and possible deaths of volunteers may feed the resistance of those who refuse to be vaccinated in general, or who may refuse to be vaccinated under a program run by the current president’s administration.

There is at least some legitimacy to all of these points. So far, that has been enough to keep the medical establishment from departing from its usual drug trial protocols. Dr. Francis Collins, who heads the National Institutes of Health, expressed his reluctance at least as far back as May, when the first vaccines were still far from entering phase 3 testing. Despite substantial lobbying from some corners of the scientific community, he has thus far not changed his public stance, though he’s said that challenge trials are at least “on the table for discussion.” The Food and Drug Administration would also have to approve a challenge testing protocol.

President Donald Trump recently criticized the FDA for, in his view, slow-walking progress on COVID-19 to hinder his own re-election prospects. His theory of the bureaucracy’s motivation is demeaning, paranoid and (almost) surely wrong. His broader theory of the case, that the bureaucracy needs to break hidebound habits to address the pandemic with appropriate creativity and vigor – such as with this week’s emergency use authorization of convalescent plasma therapy – is not.

The world needs a vaccine ASAP. Every day of delay means more people die who otherwise would not. We know this will happen; we just won’t know their names. There are many others who suffer for lack of vaccine even if they are not infected with the novel coronavirus. The pandemic creates countless victims of substance addiction, mental illness, physical abuse, and disrupted livelihood and education as it drags on.

We send volunteers into danger every day for the greater public good. First responders like police and firefighters put themselves in harm’s way as a matter of course. So do soldiers. Ambulance crews, doctors and nurses knowingly expose themselves to COVID-19 whenever they report for work in this pandemic. No small number of them have been sickened and killed. Bus drivers, grocery clerks, meat packers and innumerable other essential workers are either volunteers or draftees, depending on one’s point of view, in the fight to keep society functioning amid varying degrees of lockdown.

The perfect is the enemy of the good – in this case, the greater good. In a perfect world, we could guarantee the safety of every vaccine trial volunteer. In this imperfect world, we can only guarantee that we will do our best to be careful, and that some will suffer despite our best efforts. The volunteers who want to take part in COVID-19 challenge trials are offering to take their chances for the same reason other brave people take risks they could easily avoid.

It isn’t clear how much time challenge testing can shave off the standard trial process, but it is not reasonable to think it would have no effect at all. Sometimes, the greatest challenge is to be willing to do something different when the situation warrants it. That is the case now, even if it isn’t a no-brainer.

Larry M. Elkin is the founder and president of Palisades Hudson, and is based out of Palisades Hudson’s Fort Lauderdale, Florida headquarters. He wrote several of the chapters in the firm’s recently updated book, Looking Ahead: Life, Family, Wealth and Business After 55. His contributions include Chapter 1, “Looking Ahead When Youth Is Behind Us,” and Chapter 4, “The Family Business.” Larry was also among the authors of the firm’s book The High Achiever’s Guide To Wealth.

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