The case to infect volunteers with COVID19 to accelerate vaccine testing Nir Eyal
please welcome near a all thank you very
much Chris for the opportunity to
present this and I’m really enjoying the
discussion so far with thousands of
people dying globally every day from
coronavirus and thousands more condemned
to death by its disruptions think about
how much in life we could save by
adopting testing methods for vaccines
that are accelerated suppose we could
shorten time to roll out about one day
or by several months here’s the
conventional way to test the efficacy of
vaccines that the slowest part of
vaccine testing you distribute the
participants to people who get the
vaccine versus people who get a control
and then they go back to their homes and
you wait you wait until there are enough
exposures out there to the virus to
start seeing differences meaningful
differences between these two groups
which might allow you to conclude that
the vaccine is much more helpful for
preventing infections than the control
but my colleagues Marc lips H Peter
Smith and myself have proposed what
would be potentially a faster method and
one is more immune to the worry that
arose recently in a conventional vaccine
trial that the hotspot will move away
before you even reach a statistically
meaningful result here’s what we propose
it’s called a challenge trial and indeed
as Chris said what happens after you
distribute the vaccine to some people
and the control say the placebo to
others is you deliberately infect
everybody or they expose everybody to
the virus soon thereafter you will see
results
and be able to tell whether the vaccine
gives you greater protection then the
control in terms of say infection rates
you’re asking ourselves what’s going on
here this is very risky surely I’m a
bioethicists
aren’t I concerned people wouldn’t die
or get very sick in this trial well how
can we justify such a thing I think that
there is a way to justify it ethically
because there is a way among other
things to make the level of risk one
that we should agree is tolerable there
will be risks but they will remain
tolerable what is tolerable risk why
should there ever be risk in medical
practice medical research well we do
tolerate risks in some context think of
kidney donation everybody agrees that
live kidney donation for the purpose of
sustaining the transplantation system is
a good thing although it gains nothing
medically for the donor and there are
some risks the risks are that there is a
word a death in one in 3,000 cases of
donation let’s talk about the risk in
channel trials for coronavirus vaccines
if they are done in the best possible
way everybody is or most everybody is
likely to get infected but in the
general population
if you select young people say people in
their twenties for the trial we can look
at the number of deaths among people who
are in their 20s in the general
population and that number is lower than
the deaths from live kidney donation it
is 1 in 12 thousand cases so by simply
focusing on that age group alone in the
challenge crowd you’re already getting
to a tolerable risk level if kidney
donation is tolerable which surely it is
furthermore for this trial we should
select people who are not just the
average 20 something-year-old with
competent for rational decision making
and fully informed etc also you should
probably to minimize the risk further
exclude people who have the
preconditions that inclined people to
have severe covent outcomes such as
death once you do that the number should
go we don’t know the number of it should
go
seriously below 1 in 12,000 probability
of death upon that infection and
furthermore I think it would be right to
select the participants not from the
ranks of people who are very unlikely to
get infected at any point but rather
people who are in front-line professions
people who reside in big international
urban hubs were infection in some future
wave and there will be many waves before
we reach hurt immunities in some future
wave is fairly likely so they wouldn’t
move from 0 to 100% of infection or near
hunt percent they would move from
something much closer to a hundred
percent to 100 percent that also further
lowers the net added risk from
participation once you do those things
you get to a level of risk that is far
lower than that of kidney donation in
kidney donation we allow it because it’s
good for one other person and the donor
gives you very fully free and informed
consent and autonomously agree to
undergo a certain risk for somebody
else’s sake the difference is that in
this case we’re talking about not just
one person aided by this but potentially
many thousand saved from death or from
pravesh ment and that is a sort of
balance that from a population level
bioethics seems to me acceptable thank
you fascinating stuff so help me
understand this like let’s first of all
just look at some of the basic math
again I think currently there’s about
four or five thousand people a day dying
from coronavirus that number may plateau
down but it’s just as likely I think to
plateau upwards and so in a month that
means of the order
150,000 people might die and so you know
that’s a huge number of lives at stake
according to when a vaccine becomes
available right that’s the foundation of
the argument in many ways and yet people
behave so strangely in ethics around
numbers in the famous trolley car
experiments people will most people will
agree that they would flick a switch
that would divert a train onto another
track and kill a person if they knew
that that would save five people on the
other line but they wouldn’t for example
push a large person over a bridge onto
the track to stop the train even if they
knew that would also save lives there’s
that we differentiate between
intentional acts that put individuals at
risk and yet so this is like a troy one
of those trolley car experiments but
with on the one hand saving maybe one or
two lives if we’re unlucky if we don’t
do the challenge trials and and
potentially sacrificing hundreds of
thousands of lives through inaction I’m
it is that one crazy way of framing this
the ethics of action versus a mission
and intention versus mere foreseen
effect is very complex in this case I
believe that there is a strong case for
doing it just I’ll throw some pointers
about the general context the trolley
problem wouldn’t be the same if the
person who we are mulling over whether
to sacrifice for the sake of others
would tell us look I’m willing to do it
nor would it be the same if the risk for
them because we selected them in the
right way is very small indeed and we
know that for some individuals out there
populations at risk you know racial
minorities older people people who can’t
easily avoid leaving the work play so it
can’t really easily avoid the workplace
and need to put themselves at risk etc
for them the stakes might be higher than
for this individual
in this particular case I would kind of
cut to the chase and say look look at
the analogy of organ transplantation
look also the analogy of medical trials
that do something very similar they put
healthy people at risk so we can develop
drugs and vaccines for example the
safety trials that these vaccines that
we are talking about now have already
undergone in part which were done in
healthy volunteers who stood nothing to
gain from being given this dose of this
vaccine they only stood to gain a
certain risk it was a first in human
vaccinations nobody objected and said
that’s immoral although they put
themselves at risk to help all of us
with their full consent there are adults
complaining the risks and there are ways
to ensure that and we accept those
things it’s not ideal but there is no
other way to generate vaccines and I
would apply the same to Jones grouse
much of the medical establishment is
passionately wedded to the to this sort
of principle Hippocratic oath of first
do no harm how would you describe the
the ethics of that oath at a time of
global emergency again a complex complex
issue I want to stress two things first
that the number of people the dramatic
number of people who could be aided by a
faster method of testing vaccines
matters and second that it’s not the
only argument we mobilize it’s not
simply an argument of to bread to make
an omelet you need to break eggs the
argument is very much respectful of the
consent of these individuals of the
ability to after minimizing the risk by
focusing on the lower risk populations
and by providing excellent care in the
trials bringing down the risk to an
acceptable level so it’s not the case
that we are violating the rights of
individuals to maximize utility or
things of that sort
we’re both maximizing utility and
respecting rights and this marriage is
very very compelling in defending the
use of these accelerator designs so
we’ll take a couple of questions from
our community can you pop those on
screen so here’s one how would you get
people who’ve been marginalised by
medical science and vulnerable groups to
participate how do you cope with in
factoring privileged and process this is
an excellent question it brings up some
complexities because there are things to
gain and things to lose from involving
more marginalized populations from
focusing on on populations which are
more franchised and here are some of the
complexities I’ll to throw around and
some issues you wanna you wanna have
study participants who are very likely
to comprehend the risks very fully that
goes nicely with highly educated
participants um you don’t want to
exploit people who are participating
only because they think that they would
get money out of it my own preference
would be not to pay in this trial but
there are other people think that we
should be who don’t have any
alternatives for their care however on
the other hand you also want to ensure
that
constituencies of marginalized
populations of global marginalized
populations can have this claim and say
we participate in this trial now give us
these vaccines or that we will have
tested biologically that this works in
different types of human bodies
including not always the bodies of the
people who are most enfranchised so it’s
a complex balance sometimes there is
correlation I mentioned earlier I think
it will better to test the vaccine in
people who otherwise are likely to get
infected unfortunately in our very
unjust world that often correlates with
prior disadvantage so it’s not
exploitative not exploitative the far
the exact balance might be something
like try to focus on people who
otherwise
would probably get infected but are not
the most marginalized while guarding and
ensuring the quality of informed consent
it’s complex but these are exactly the
kinds of thoughts that we should be
having right now and one more question
how do you prevent or mitigate
unnecessary deaths with challenge trials
especially in a fast-track setting like
this so first it’s about the selection
criteria you want to focus on people who
are young and otherwise free from risk
factors hypertension obesity etc the
tend to correlate with bad outcomes from
the disease there is no guarantee that
nobody will develop severe kovat that
nobody will die but you can really
decrease dramatically the chances that
this will happen when you do that second
you want in the trial to provide the
best medical care available for this
disease by the time this happens there
might be novel therapeutics they might
be scarce first access to this I think
you no decency should be in the trials
so that we know that in return for this
person volunteering to get the trolly
earth it’s actually much less dramatic
than that get the risk of being hit of a
trolley and it’s a small risk I argued
we ensure that we treat them the best
way we can and that’s not just I would
propose knighting them decorating them
but also given the best possible care
and engaging them in discussions they
are agents they’re not guinea pigs
engaging them in the planning of what
will happen in these trials the
nonprofit one day sooner has I think
already recruited
I mean tens of thousands of volunteers
willing to participate is that how
should society regard this I mean at the
moment the the conversation seems over
weighed by fear of a death isn’t there
another scenario where we basically
recognize people willing to do this as
as heroes and celebrate them the same
way you know we might celebrate someone
who was going off to fight a noble war
or you know do something heroic for
like an astronaut who’s willing to risk
their life to go into space
you know we celebrate those people I
just wonder whether there’s any way of
actually changing the narrative and
whether that would make a difference to
accelerating the possibility of these
things actually happening I couldn’t
agree more I’m imagining that with these
people and they’re I mean I’m floored by
their courage by the intelligence the
leadership knows much more about many
technical aspects of these trials than I
do they’ve explored it seriously
academically many of them are graduates
of the best universities in the world or
teachers and the best universities in
the world and an amazing combination of
of courage intelligence good intentions
and if the volunteers come from these
ranks high chance of really
comprehending consent they know what
they’re getting into and I think every
every ground for the highest honors that
our societies have we’ll take one more
question and then I’m gonna bring back
dr. Kim and David and we’ll have a
four-way conversation so let’s have the
next conversation from our community
it’s coming I tell you what let’s not do
that let’s bring back talk to Kim and
David and just continue the conversation
because I I I have a question for dr.
Kim on this as to how how he views the
status oh you know what the question
popped up with organ donations which
have we have a long history of knowing
the rest based on actual data how do you
figure this out in this novel case
before you really know those risks great
question there was a time by the way
that for organ donation we allowed it
and we didn’t know the risks quite yet
this is the nature of science um there
are many unknowns for an emerging
infection I think in this case we
already have the bottom line number the
bottom line number is the biggest risk
in these trials is comes from the
infection and we know that if you focus
on the
of an age group we know what in the
general population in a developed
country with access to critical care etc
that number is roughly and it’s roughly
one in 12,000 which I argued is already
a tolerable risk level and the number
should be below that there are further
unknowns sometimes even that group
people die young people sometimes die of
this you healthy young people do it’s
very rare but when they do we don’t know
what was exactly responsible was it a
you know special gene or whatnot the
bottom line risk level for that group is
the number that is most pertinent for
the decisions about the risk for a group
where you do not know what genes people
have we don’t know what genes they have
to put them at risks here