The Moral Case for Testing Coronavirus Vaccines through "Challenge Trials" on Paid Healthy Volunteers

Doing so can potentially save many thousands of lives. And moral objections to this practice are weak. The issues here are very similar to the longstanding debate over whether we should legalize organ markets.

By now almost everyone recognizes how vital it is to develop an effective coronavirus vaccine as quickly as possible. A vaccine would save many thousands of lives that are otherwise likely to be lost to the virus. In addition, developing a vaccine may well be the only way to overcome the worldwide economic crisis caused by the disease. Even if lockdown orders are lifted, many people will still be unwilling or unable to return to anything like "business as usual" for so long as the coronavirus remains a threat.

The costs here are not just narrowly "economic." They also involve such things as foregone medical treatment leading to increased death from non-covid causes, growing hunger and poverty (especially in developing nations), and a reduction in childhood vaccinations that could imperil millions around the world. Anything that can make a vaccine available even a month or two earlier than would otherwise be the case could save a great many lives and avert much suffering.

But, in order to swiftly develop a vaccine, it may well be necessary to resort to "challenge trials": deliberately infecting healthy volunteer test subjects with the virus in order to then determine whether candidate vaccines work on them. My George Mason University colleague, economist Alex Tabarrok explains the reasons why here:

What if we develop a vaccine for COVID-19 but can't find enough patients to run a randomized clinical trial? It sounds absurd, but this problem has happened in the past. Ebola was identified in 1976, and candidate vaccines were proven safe and effective in mice and primates in 2004 and 2005, respectively. But no human vaccine was produced because it was extremely difficult, bordering on impossible, to trial an Ebola vaccine. The problem? Ebola is so deadly that people take precautionary measures long before a vaccine can be tested…

Vaccines are intended to prevent disease in healthy people, so they're tested for efficacy in healthy populations. But to test a vaccine, you need a population of still-healthy people who might get sick…

When a COVID-19 vaccine is available, it will be necessary to find a large population of people who are still at high risk of contracting COVID-19. This may be difficult. In developing countries, which may not be able to contain the virus, herd immunity may have developed. In richer countries, social distancing, testing and other measures may have made the probability of infection relatively low….

Even health care workers, however, have a low enough infection rate that you either need many months to determine if there is a significant effect, or you need large populations….

There is a second, related problem. Historically, most vaccine candidates fail. Thus, in a year or two, we want many vaccine candidates, not just one. But even if we are fortunate and have, say, seven vaccine candidates available, it probably won't be possible to run efficacy trials on all seven candidates….

The efficacy-trial bottleneck motivates the use of challenge trials. In a challenge trial, healthy individuals are split into two groups, one half vaccinated, the other not, and then both groups are infected or "challenged" with the virus. No waiting for natural infections here…

The virtue of a challenge trial is that the results would be available very quickly, within a few weeks, and using only a small population. If the vaccine is 50 percent effective, for example, then we would need around 100 volunteers or perhaps even fewer depending on how many people exposed to the virus in laboratory conditions contract the disease.

As Alex points out, these problems may foil early production and deployment of a promising vaccine candidate currently under development by scientists at Oxford University.  Challenge trials can fix this issue.

In this Washington Post article, philosophers Richard Yetter Chappell and Peter Singer make a strong utilitarian consequentialist case for challenge trials: the risk to the volunteers is greatly outweighed by the enormous benefits to others. There aren't many issues where Tabarrok - a libertarian - agrees with Singer (who is far more left-wing)!

Chappell and Singer are right in so far as they go. Any plausible cost-benefit analysis comes out the same way. But non-utilitarians might still have reservations, such as fears that paying volunteers to participate in challenge trials might lead to exploitation of the poor, "commodification" of the body, or the use of test subjects who are ignorant of the risks.

The challenge trial debate, gives me a strong sense of deja vu. For many years, I and others have argued that the government should legalize the sale of organs, so that thousands of lives can be saved - and much other suffering prevented - by increasing the number of organs available to those who need transplants. The arguments in that debate are very similar to those that can be raised against coronavirus vaccine challenge trials.

Thus, answers to standard objections to organ markets can also help justify coronavirus challenge trials. Consider, for example, the claim that paid challenge trials will exploit the poor. I answered that objection in the organ market context here:

[M]any people oppose legalizing organ markets because they believe it would lead to exploitation of the poor. But most of them have no objection to letting poor people perform much more dangerous work, such as becoming lumberjacks or NFL players. If it is wrong to allow poor people to assume the risk of selling a kidney for money, surely it is even more wrong to allow them to take much greater risks in order to increase their income.

If you believe that organ markets must be banned because they exploit the poor, you must also argue that the poor should be forbidden to take jobs as lumberjacks and football players. If you believe that such considerations justify banning participation in organ markets even by the non-poor, than we must also categorically forbid monetary compensation for football players. Indeed, the case for banning the payment of football players is actually much stronger than that for banning organ markets. Unlike the ban on organ markets, a ban on professional football would not lead to the deaths of thousands of innocent people.

If you still worry that the poor will be "exploited" in either organ markets or challenge trials, I offer the second-best solution of restricting participation in such markets and  trials to the nonpoor. Simply adopt a rule that all test subjects must have incomes above whatever threshold you think is enough to avoid "exploitation" (e.g. - above the poverty line or above the average income in the participant's country).

We do not need an infinite supply of volunteers for challenge trials. Just a few thousand. It should be possible to find them even if participation is limited to those above a certain income floor. As of this writing, the admirable "1 Day Sooner" website has already gathered over 25,000 volunteers who are willing to participate. Many, perhaps most of them, are not poor. And surely we can find more such volunteers, if need be.

Here is my response to claims that paying organ donors (and by extension Covid challenge trial participants) will somehow unjustly "commodify" the body:

Other critics believe that organ markets must be banned because it is inherently wrong to "commodify" the human body. Yet most of them have no objection to letting a wide range of people profit from organ transplants, including doctors, insurance companies, hospital administrators, medical equipment suppliers, and so on. All of these people get paid (often handsomely) for helping transfer organs from one body to another.

Perversely, the only participant in the process forbidden to profit from the "commodification" of organs is the one who provided the organ in the first place. If you believe that people should be forbidden to sell kidneys because earning a profit from organs is immoral "commodification" of the body, you must either oppose paying all the other people who currently earn money from organ transplants, or explain why they, unlike the original owner of the kidney, are not also engaged in commodification…..

What is true of organs is also true of vaccines. Scientists, drug manufacturers, doctors and others stand to profit from the development of a Covid vaccine, which necessarily involves human trials of one type or another. Challenge trial participants should be allowed to do so, as well.

I would add that we pay volunteers to risk harm to their bodies in many other contexts. Soldiers, police, firefighters, lumberjacks, coal miners, and professional football players are all examples. Participants in many of these professions accept greater risks than organ donors or young, healthy Covid-19 challenge trial participants are likely to undergo. If "commodification" is fine for lumberjacks, police, and firefighters, it should be permissible for challenge trial participants, as well.

There is, of course, a danger that some participants will not be properly informed of the risk. But that can be minimized by securing "informed consent" ahead of time, as is already required for medical procedures.

The information available to participants may well be imperfect. Covid-19 only appeared a few months ago, and there are still uncertainties about its effects. But we allow people to voluntarily take imperfectly understood risks for pay in many other contexts. For example, soldiers and police often do not know ahead of time exactly what sorts of dangers they may face in the course of doing their jobs. It is notoriously difficult to predict what risks may arise in future battles. The moral requirement of informed consent can surely be satisfied if volunteers are given the best information available at the time, and also informed that there are some risks involved that experts may not yet fully understand.

It is also worth noting that there are already volunteers available who do have a solid understanding of the risk, and who are not readily dismissed as desperate poor people ripe for "exploitation." Consider, for example, this article by Princeton student Isaac Martinez, explaining his willingness to volunteer, or this one by Bloomberg columnist Faye Flam, discussing her decision to do so.

There may be some who object to challenge trials even if the participants are not paid, on the ground that it is intrinsically immoral to deliberately subject healthy people to the risk of a deadly disease, even if they consent. But, as already discussed, we routinely allow volunteers to take risks with their lives and health in a variety of other contexts, including many where the potential benefits are far smaller than here. If it is not immoral to allow soldiers, police, and firefighters to take such risks, the same goes for challenge trial participants.

Like others who risk their lives to benefit others, challenge trial volunteers deserve our gratitude, and proper compensation for their efforts. And there is no good moral justification for forbidding them to take those risks. To the contrary, we should move ahead with challenge trials as soon as feasible. Every day of delay could literally be a matter of life and death - a great many lives and deaths.

Comments

[Dr. Ed]

What about prisoners seeking a pardon?
How about sex offenders -- a totally clean slate in exchange for volunteering.

[librarian]

In the same way a guppy is just a little whale.

[Dr. Ed]

A whale is a mammal.
Fish are not...

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[librarian]

Someone should sue the FDA for negligence.

[anorlunda]

"utilitarian consequentialist"

Is there no cure to the academic speech impediment syndrome?

[LawTalkingGuy]

Those are pretty old and straightforward descriptive terms. I wouldn’t put them in the category of nonsense academic jargon.

[Bob from Ohio]

"philosopher...Peter Singer"

A man who believes we can murder newborns.

[Brett Bellmore]

Pretty much everybody believes we can "murder" newborns. Singer believes we can't, that's the problem.

[The Turtle Dove]

Absolutely not. Here's why: If I accept a harm because I know that there will be a benefit from it, the equation is H<B. If I accept the proposition that the government will harm someone because it is the least oppressive means of acquiring a desired benefit, the equation looks like this: H(A)<B(B). To determine this, I need to know what relation A and B have, and that's G, for government. G(A)=G(B), if all's going well in the commonwealth. So the relation of A and B is that the constant of G has to have the same relation to both. I can therefore substitute in and have the condition H[G(B)] < B[G(A)]. A should accept the harm only if B, put in their place, would see it as their logical civic duty to ensure that A is accrued a civic benefit. And when wealth is unequal, B would often refuse this proposition.

In short, the harm/benefit calculus works as a function of government's relationship to its people. And to state the obvious, when the poor are exposed to a deadly disease for the benefit of those who (by the very fact that they haven't signed on) would not incur similar risk to assure that the poor accrue the civic benefit, while there might be a libertarian, open-markets argument for the survival of the wealthiest, there certainly isn't a moral argument here based on civil society or law.

Mr. D.

[Krayt]

If more die because you kept your morals, I'd question your morality.

[The Turtle Dove]

Your best argument in that case, though, would be that it is immoral to have morals, which is inherently contradictory.

You'd need a new idea of shared right to disprove any idea of shared right. Rejecting morality itself on moral grounds amounts to abandoning reason.

Mr. D.

[Commenter_XY]

I disagree. An autonomous individual is free to make their choice. Their body, their choice. You have nothing to say about it, as a moral proposition.

[The Turtle Dove]

Except for the fact that this is a government initiative to address a matter of public concern, not a private group's detour or frolic in search of better mousetraps to make money. Where the people are sovereign, both the one risking the harm and the one benefiting from it must believe the government's action to be moral.

Mr. D.

[Commenter_XY]

Again, I disagree. As an autonomous individual, I (and I alone) choose to participate, or not. I as an autonomous individual weigh the risks and benefits. I decide whether the government's actions are moral or not. I am the one taking the risk. You have nothing to say about that.

So long as there is transparency, an exchange of value for value, then there is a contract and you are not a party to it. It is neither illegal nor immoral.

[The Turtle Dove]

I do, however, have grounds to challenge the government's operation of the trial and my participation in the benefit. Would you have the right to participate in a high-stakes poker game, cockfight, or slave auction in the mayor's office? Perhaps, but I would have a moral objection to the use of the office, and if my reservations were based on the criminal code of the state, I'd have a right to expect your agreement with that, as a fellow citizen of the state. If the drug trial isn't against the criminal code (actually, it probably is, but arguendo), I would similarly expect your agreement with my objection if it implicated fundamental constitutional principles such as the equal protection of the law.

There is a clear moral claim on someone in a commercial transaction that they think is fair and transparent, and for which they have received value, so long as they wish to remain part of the state that preserves the equity of such transactions.

(Otherwise, the mayor might use a marked deck.)

Mr. D.

[Squirrelloid]

So, let the private drug companies run the trials, and don't involve the government in it?

[The Turtle Dove]

If the government had absolutely no role -- it wasn't funding it, and it wasn't using the company to produce something essential for the country as a presumptive customer of the product, you're right, there would be a different standard. We'd then look to the corporate charter of the company -- every private company is technically an instrumentality of the state, or created for the benefit of the people of the state, and therefore entitled to go about its business according to the term of its charter, usually for any lawful purpose -- and make sure that it wasn't doing anything egregiously illegal, unconstitutional, or hazardous. (Plantation slavery, death penalty for violation of the neighborhood building appearance code, etc.)

Mr. D.

[Commenter_XY]

You seem to miss the point. I'll try one last time.

You seek to impose your standardless, arbitrary values on a contract between two other parties. That is immoral. If two autonomous parties are transparent, exchange value for value, there is a contract. And you have no moral claim on it. Period.

Mr. Turtle Dove, you have yourself a nice day. And don't go nosing into someone else's business (contract). 🙂

[The Turtle Dove]

I'd just observe that your standard would permit indentured chattel slavery, contestants fighting to the death for the purposes of entertainment, and the domination of every part of the broadcast spectrum by pirate station broadcasts of Magnum, P.I. reruns.

Mr. D.

[Krayt]

Lots of words. What's the death count?

[The Turtle Dove]

About 150,000 per day, caused by man's sin. Almost all of whom worked painfully hard for most of their life, hoping for a better world.

Mr. D.

[LawTalkingGuy]

Assuming time and practicality were not material, which they are obviously, the most moral approach to future vaccine challenge trials, organ markets, and dangerous jobs is to not have society where the existence of those things is a necessity for the survival of the volunteer. It shouldn’t be necessary for someone to accept risks like that merely to avoid hunger, homelessness, or pay for another type of life saving care for themselves or a loved one.

Dangerous risks should be accepted based on a reward beyond the “reward” of having basic needs met. So there shouldn’t be an income barrier to these things because that takes away another opportunity to meet those needs.

Of course, this approach doesn’t help the immediate needs of the population generally for the covid vaccine or specific individuals waiting for organs or who will be in the future. So I think
I actually agree with Ilya that it’s probably best to open things up, with the caveat that we should be working towards a society where the potential volunteers aren’t weighing the risks with the belief that their basic needs may depend upon it.

[Commenter_XY]

Minimally, compensate the volunteers with a life insurance policy that will pay out if they die from the failed vaccine.

[Stephen Lathrop]

If you believe that organ markets must be banned because they exploit the poor, you must also argue that the poor should be forbidden to take jobs as lumberjacks and football players.

So you think the NFL is combing the slums of Calcutta for Tom Brady's replacement? Problem is, exploitation via football—which is pretty alarming if you look closely—is nowhere near the nightmare that a mass market in organs would deliver. In football, the personal rewards sought are out-sized, and the candidates few. It's a matter of scale. Even adding the lumberjacks doesn't much dilute that problem. There never were that many lumberjacks. They are mostly gone now.

But, as already discussed, we routinely allow volunteers to take risks with their lives and health in a variety of other contexts, including many where the potential benefits are far smaller than here.

Keep your eye on the pea. In the former context there is a considerable benefit to the volunteers themselves. In the challenge trial context, it is society generally, armed as it is with means of compulsion both subtle and blunt, which gets most of the benefit. Nor do I think you can much improve that situation by re-balancing scales, or sweetening pots. Pay each volunteer $10 million? Doesn't that just make the problem more vivid?

Perversely, the only participant in the process forbidden to profit from the "commodification" of organs is the one who provided the organ in the first place. If you believe that people should be forbidden to sell kidneys because earning a profit from organs is immoral "commodification" of the body, you must either oppose paying all the other people who currently earn money from organ transplants, or explain why they, unlike the original owner of the kidney, are not also engaged in commodification…..

That paragraph starts with the right word. The people facilitating transplants—unlike the donors—are not being harmed in the process. They are profiting. The role of a transplant surgeon, however equivocal you think it is now, will be a lot more troubling when the organs he installs get harvested as a means of capital punishment, in for-profit prisons. Nor would paid volunteer donors be practicing commodification. They would be victims of it.

The one good idea is the notion of a socioeconomic threshold for volunteer donors. But even there, the OP is weak. Above average income? Come on. That's pitiful.

The need is assurance that volunteers are absolutely free of compulsion. Not many people are. Look for threshold donors who personify the opposite of compulsion. That opposite is power. You want a dramatic, ethically unblemished demonstration of self-sacrificing heroism? Let U.S. Senators lead the way as challenge trial subjects. Throw in some Supreme Court justices.

What good will it do if challenge trial subjects were near-certain to recover anyway? A Mitch McConnell recovery would provide a hundred times more proof of efficacy than some self-sacrificing 30-year-old med student.

[Commenter_XY]

This is a terrible idea = The one good idea is the notion of a socioeconomic threshold for volunteer donors.

If I am poor and educated, why would you deny me the ability to lift my family out of poverty, by choosing to take an informed risk? I don't think you get to make that call for another autonomous individual, as a moral proposition.

[David Nieporent]

That paragraph starts with the right word. The people facilitating transplants—unlike the donors—are not being harmed in the process. They are profiting

So are the donors in a system where they get compensated. They get something they value more — $ — in exchange for something they value less - a kidney. That's pretty much the definition of profit.

[Stephen Lathrop]

My accountant insists on a different definition.

[bernard11]

I have a different concern. What does a successful challenge trial prove? That the vaccine works for young healthy people.

So it seems shaky to assume it will work, or be safe, on older, sicker people. That doesn't mean the challenge is worthless, but there seems to be a step missing between that and widespread deployment.

[neurodoc]

"What does a successful challenge trial prove? That the vaccine works for young healthy people." It proves that the vaccine elicits a protective immunologic response. But that immunologic response may be weaker in older adults, which is the case with some vaccines line the annual flu ones that have a stronger version for those over 65. If it is possible to develop an effective covid-19 vaccine, which we don't know we can yet, it will remain to be seen how good is the protection it affords to different groups and how enduring the protection is. We hope for the best, but there is no guarantee of it with a novel organism.

[ReaderY]

Professor Somin,

Why not be honest about it and support gladiatorial combat?

If social benefit outweighs human life even for the healing profession, how much the more must it do so for ordinary tradespeople like entertainers. Who is the state to tell people they canmt consent to fight to the death for people’s entertainment if their families will be paid enough for it and they can find work elsewhere?

After all, as Maximus put it, are you not entertained? Are you not entertained? Is this not why you are here?

The Essence of the conventional morality of Western civilization is a belief that there in fact some of other reason why we are here. That is why gladiators are banned, and why healers don’t kill.

But what business is that of the state? Why not be honest?

[Gasman]

Phase 1 clinical trials are tests of new interventions in patients for whom there is no expectation for individual benefit; at least researchers should err toward underselling patient expectations. Participants may hope for a grand-slam, but most phase 1 trials strike out looking. The principle aim of Phase 1 is to determine in a small population whether an intervention is safe enough to move forward to seek efficacy(phase 2), and identify common toxicities and where applicable, the dose that produced some measurable effect/side-effect.
The rate of injury and death is not trivial. Ethics for voluntary participation is not so much a debate, as long as the participation is voluntary, and the subject is fully informed of basically all that the researchers know. Prisoners are almost categorically not permitted to be study participants, because it can be difficulty to ensure that it is voluntary without any actual or perceived coercion. Exception for prisoner participation would be where there is some greater prospect for individual benefit, but then that would be phase 2 or phase 3 studies.

I agree with commenter_xy that compensation should cover the subject's potential future costs, including payment for death to their dependents, and disability insurance, either of which must be sufficient to make them fiscally whole.

[mydisplayname]

I agree that May 16 passed without many noticing its significance. The purportedly moral case has been made many times before... and one day the moral argument might prove itself actually moral.

https://apnews.com/e9dd07eaa4e74052878a68132cd3803a/AP-WAS-THERE:-Black-men-untreated-in-Tuskegee-Syphilis-Study

[jack murphy]

unless we get demographic info to accompany each death the news is not helpful. age, co-morbidity, etc. we have all failed to demand timely info and as a result the media has buffaloed the nation into submission before a non-threat

[Sanjose Mike]

How would this metric change if, by the end of the year, advancements in therapeutics cured MOST cases of Covid, even including elderly people? Which is what we are already starting to see.

And secondarily, the virus does not come back to any significant degree in the Fall, making a vaccine irrelevant?

Sanjosemike (no longer in CA)
Retired surgeon

[Harry w]

Wearing a mask could reduce the chance of being affected by covid. This pandemic crisis has been changing many things in our everyday lifestyle. The Chat Hispano has been also becoming popular during these terrible days. I hope these horrible days will be ended soon and we will get an effective vaccine against this pandemic coronavirus.