The New York Review of Books - USA (2020-08-20)

August 20, 2020 61

LETTERS

THE TRUE COST OF
VACCINE STUDIES

To the Editors:

Carl Elliott uses a review of Adverse
Events: Race, Inequality, and the Testing of
New Pharmaceuticals [NYR, July 2] by the
medical anthropologist Jill Fisher to discuss
a dilemma between two designs for effi-
cacy studies of vaccines against the novel
corona virus.
Traditional designs to study vaccine effi-
cacy are slow and can end without having
reached statistically meaningful results.
A challenge design may be substantially
faster, or so the two of us (along with Peter
Smith) have argued.^1 The main risks in a
challenge study are greater per volunteer
but can be brought down dramatically by
recruiting only young, healthy volunteers.
Either trial type risks accidents from the
test vaccine’s toxicities or its enhancement
of disease severity. In a traditional design,
such accidents could happen to many more
participants and take place in the field, not
in the relative safety of a controlled med-
ical environment. Challenge studies for a
Covid-19 vaccine could help get us out of
the current global pandemic faster, saving
an incalculable number of lives and end-
ing its disruptions of health care, food, and
economic development, so they are worth
considering.
While Elliott nowhere states his conclu-
sion, he is clearly against challenge studies.
That position is ill supported by his argu-
ment that there are both historical and
present abuses in medical research. He
traces a history of abusive Phase I trials,
mainly for drugs, including nonconsensual
trials that preyed on vulnerable prisoner
populations before the current regulatory
framework was introduced. He also points
out some genuine problems in the current
US system for medical research.
But how do these considerations even
begin to answer which of the two efficacy
trial designs now under consideration is
preferable? To be sure, our article sug-
gested that in these vaccine challenge tri-
als, “multiple measures...be put in place to
ensure that prior to consenting, potential
participants fully comprehend the unusual
risks involved in the study.”
It is true that challenge trials carry serious
risks. But there are risks in either study type.
Either can be done ethically or unethically.
Elliott insinuates that we neglected ques-
tions of payment to study participants. Our
priority in the paper was to explain how to
select participants with minimal likelihood
of dying. Our dozens of later newspaper and
TV interviews have repeatedly addressed
questions of payment. While the matter is
complex, our position resembles the one
preferred by Elliott: payment for the risk
taken would be a bad idea, although volun-
teers should be compensated for any acci-
dents (which remain unlikely). They should
be sustained and perhaps compensated for
their long period in isolation but should not
be lured by mammon to a risky trial. Again,
though, why doesn’t Elliott direct the same
critique at the traditional way of studying
vaccine efficacy?

Nir Eyal

Henry Rutgers Professor of Bioethics

Rutgers University

New Brunswick, New Jersey

Marc Lipsitch

Professor of Epidemiology

Harvard T. H. Chan

School of Public Health

Boston, Massachusetts

To the Editors:

In “An Ethical Path to a Covid Vaccine,”

Carl Elliott discusses the growing call for

“challenge studies” to test a potential vac-

cine against Covid-19. These would involve

clinical trials of volunteers in which all of

them receive the vaccine, but half are also

deliberately injected with the virus. If the

infection rate is no higher in this group,

that would show that the vaccine is effec-

tive. The alternative is a typical and neces-

sarily longer trial, in which the rates of nat-

urally acquired coronavirus infections are

compared in vaccinated and unvaccinated

groups.

Elliott seems to think challenge studies

would be acceptable, provided there are

stringent protections and compensations

for volunteers who might be harmed by

being deliberately injected with a danger-

ous virus. Since he believes those neces-

sary measures are extremely unlikely to

be enacted, he is opposed. I admire Elliott

greatly, so it’s difficult to argue with his

thoughtful analysis, but I will. I don’t be-

lieve the door to challenge studies should

be left even ajar.

There are two specific problems with

even the most carefully done challenge

studies of a Covid-19 vaccine. First, we still

know very little about this novel virus, in-

cluding what hidden or longterm effects it

might have on even young, healthy volun-

teers. And second, will a vaccine be equally

effective in the elderly and chronically ill,

those who are most vulnerable to Covid-

19? Elliott acknowledges this problem,

but I think it may be more serious than he

implies.

But more generally, I worry about the

erosion of our hard-won ethical consensus

(starting with the Nuremberg Code) that

people should not be used as means to an

end if they might be harmed. There is also a

risk of bribery or coercion in enrolling vol-

unteers, even if they are officially unpaid. I

believe this erosion of our ethical standards,

even for a good cause, would be a very un-

fortunate precedent. We would then be on

the proverbial slippery slope downhill.

Marcia Angell, M.D.

Former Editor-in-Chief

New England Journal of Medicine

Santa Fe, New Mexico

Carl Elliott replies:

Nir Eyal and Marc Lipsitch suggest that

my aim was to discuss a dilemma between

two designs for vaccine efficacy studies. In

fact, my aim was to make sure that potential

volunteers for Covid-19 vaccine challenge

studies were aware of some critical issues

that advocates have failed to mention. First,

if research subjects in the United States are

sickened or injured in a trial, they may well

face financial ruin on top of their illness.

Most sponsors require subjects to pay for

their own medical care, and virtually none

guarantees compensation for pain, suffer-

ing, or the inability to work. Second, many

of the current industry sponsors of vaccine

trials have a record of burying, spinning,

and rigging their research. (The list of

such sponsors includes Merck, for which

Lipsitch consults.) Third, even if a trial

leads to a vaccine, we have been given no

guarantees that it will be made available to

those who can’t afford it, raising the pos-

sibility that the sacrifices made in vaccine

trials will yield benefits primarily to the rich

and well insured.

None of these problems is unique to chal-

lenge studies. What is unique about those

studies is the extraordinary number of peo-

ple willing to volunteer without being told

about the fine print. This is a recipe for

exploitation. Eyal and Lipsitch claim their

priority in their article was “to explain how

to select participants with minimal likeli-

hood of dying,” yet in the study design they

proposed, some subjects up to the age of

forty-five would be exposed to the corona-

virus after getting only a placebo vaccine.

Like Marcia Angell, I’m disturbed by

the use of subjects as a means to an end,

especially when the risks are unknown. If I

left the door to Covid-19 vaccine challenge

studies ajar, I can think of no one better

than Angell to close it. In fact, we may

need to close a lot more doors. In Phase I

trials, researchers routinely use subjects

as a means to an end, even when the risks

are significant and the subjects are vulner-

able. That slope was slippery and we have

reached the bottom. We need to find a way

back up.

THE ‘EUTHANASIA’

EUPHEMISM

To the Editors:

Michael Pollan’s “The Sickness in Our

Food Supply” [NYR, June 11] presents

a compelling indictment of the modern

American food system. But in detailing

the exploitation of workers and the deteri-

oration of consumers’ diet and health, the

article seems studiously to avoid mention

of the havoc wreaked on other animals.

Indeed, it does the opposite by referring,

twice, to the need to “euthanize” animals

by the thousands and millions because of

Covid-19 supply-chain problems.

The New York Review is a periodi-

cal devoted to the proper and best use of

language. It is therefore surprising, not to

mention distressing, to see that the editors

gave this euphemism a pass. “Euthanasia”

designates a certain type of killing having

two primary components. One is that the

killing is for the benefit of the one being

killed. The other is that the killing be “gen-

tle.” (“Kind” might sum up these two com-

ponents in a single word.)

The killing that has gone on during the

current pandemic satisfies neither of these

criteria. The animals do not desire to die.

And the methods being used to kill them

are not anything one would condone for

any of these animals if they happened to be

one’s pet (an apt proxy for humane or kind

killing); for example:

The preferred methods of euthanizing

hogs include gunshots, bolt guns or

electrocution, but when thousands of

animals must be destroyed en masse,

one option is to shut off ventilation

causing heat to build up and kill them,

said Chris Rademacher, a veterinar-

ian and associate director of Iowa

State University’s Iowa Pork Industry

Center.^2

Compounding the absurdity of using the

“euthanasia” euphemism to designate kill-

ing without qualification is to highlight the

use of it in circumstances where the killing is

simply taking the place of killing in a slaugh-

terhouse. At least the latter is straightfor-

wardly named, though I wonder when

the industry (and its critics!) will adopt a

French word to pardon its English. The only

differences between the present euthanasia

and the normal slaughter are which unkind

method of killing will be used and which ex-

ploited workers have to do the dirty work.

Joel Marks

Professor Emeritus of Philosophy

University of New Haven

Bioethics Center Scholar

Yale University

New Haven, Connecticut

Michael Pollan replies:

I’m grateful to Professor Marks for call-

ing this out: I should never have repeated

the industry’s euphemism uncritically, but

rather stated clearly that the animals were

being either asphyxiated or shot.

ECONOMICS & HUMANITY

To the Editors:

Marilynne Robinson’s essay “What Kind of

Country Do We Want?” [NYR, June 11] is

great on rhetoric as it pushes most of the

emotional buttons, but is uninformed and

incoherent. Because it is a long article, I will

only mention a few areas of concern.

Here is a quote from the first page: “The

global economic order has meant that the

poor will remain poor.” On the contrary,

the global economic order (freer trade be-

tween countries and less government con-

trol of the economy) has meant that hun-

dreds of millions of the poorest of the poor,

those in China and India, have escaped (ex-

treme) poverty, and tens of millions if not

more have moved into the middle class in

the last few decades.

Most of the article is devoted to criticiz-

ing cost-benefit analysis. Consider the fol-

lowing quotes: “The cult of cost/benefit—of

the profit motive made granular, cellular—

not only trivializes but also attacks what-

ever resists its terms.” “This theory has all

the power among us of an ideology, though

it lacks any account of past or future, any vi-

sion of ultimate human well-being.” I wish

that I had the talent to write such sentences.

Unfortunately, these statements are the op-

posite of what cost-benefit analysis actually

tries to do.

Let me first illustrate with a recent pro-

posal by Janet Yellen and supported by

3,500 economists (economics being the

intellectual source of cost-benefit anal-

ysis). This proposal argued for a carbon

tax, which would shift energy production

to more costly methods of producing en-

ergy and reduce present consumption for

the benefit of future generations. At the

same time, the proposal suggested that the

proceeds of the tax go to those with low

income. Simply put, the cost-benefit anal-

ysis argued that the benefit to future gen-

erations outweighed the cost to the present

generation. Note that contrary to the above

quotes, future well-being is taken into ac-

count and there is no discussion of profit.

In the context of the above paragraph,

Robinson’s support of the Yellow Vest

movement in France is ironic because the

spark that set off the Yellow Vest move-

ment was that individuals (not all of them

poor) were angry that they would have to

pay more for their gasoline and diesel. It

appears that the Yellow Vests were not in-

terested in future generations, but the cost

to themselves.

Robinson is in favor of raising the min-

imum wage and attributes numerous ben-

efits that would be forthcoming. Unfor-

tunately, because she does not believe in

cost-benefit analysis, she does not consider

the possibility that there might be costs to

unskilled workers from raising the mini-

mum wage, for example, fewer unskilled

workers might be employed when the min-

imum wage is increased. If wages were to

go up to the level that Robinson would like,

the price of fast food, house cleaners, and

other commodities and services provided

by low-paid service workers would go up,

(^1) “Human Challenge Studies to Accelerate
Coronavirus Vaccine Licensure,” The Jour-
nal of Infectious Diseases, Vol. 221, No. 11
(June 1, 2020).
(^2) David Pitt, “Slaughterhouses Reopen But
Farmers Still Euthanizing Pigs,” Associated
Press, May 29, 2020.