Now we're back to me,
and we're going to do a case.
My general disclaimer you've seen many times.
Imagine that.
So this is a post Covid a clinical trial
for those who are experiencing a post-Covid syndrome.
So breathe better.
Eight is a new compound meant to treat impaired lung
function.
Among those suffering from this post,
Covid syndrome, or PKS.
The investigators are proposing a multi-site, randomized,
double blind, placebo controlled trial among patients
discharged from the hospital but with lingering pulmonary
symptoms.
So these are folks who had Covid bad enough to be hospitalized,
are leaving the hospital now, going back home
but have lingering pulmonary symptoms.
The patients will be randomized to receive
or a placebo for 12 weeks, with a one year
follow up.
All patients will receive the same
background current standard of care.
Right.
So just to remind you all, the idea here is that they're
coming in
to the hospital for this clinical trial,
that they are expected
to have someone outside who is taking care of their
primary care.
But if issues come up
during the process of the study,
that is standard of care the hospital will provide for
cover.
The cost of that.
So the trial is a collaboration
between the NIH and Dameron Biologics,
a private company.
As the Covid pandemic has slowed.
The study team is concerned
about their ability to meet their targeted
enrollment goals.
So the trial is currently underway
at four in-force
in sites in four states.
One of these sites is in state X,
and they have indicated that they plan to exclude
otherwise medically eligible subjects
who are currently uninsured,
meaning they have no health insurance
coverage.
The health system of which they are a part.
Bil standard of care expenses to participant insurers.
The health system has notified the Pi
that it will not cover these expenses.
For participants who do not have health
insurance.
So here is your first question.
Is it okay for the state X site to limit enrollment in
this way?
And so the first question is just a
yes or no.
Do you think it's okay.
And we'll of course talk about, you know
further about some of the issues.
But just your gut response.
Is it okay for the state to limit
enrollment of those of you who said yes?
Or can think of a reason why?
Why did you say yes? Or if you said no?
Why do you think someone who said
yes might say yes?
Great.
So one would be to prevent too many costs to participants,
right?
If the site isn't going to cover it,
that means that the participant is going to have to cover that
expense.
Great.
So someone said I was taking this
with a very narrow perspective.
The question of like, is it legal to do this? Yes.
I think we could decide that maybe it's legal to do that,
but we're going to be talking about
whether it's ethically appropriate.
Let's see if it's done during the protocol
development
and as agreed upon by all the sites,
then maybe
that's okay.
They may not be able to get their follow
up care needed.
Right?
That's a participant focused concern.
And because it's still improve some access
to participants.
Great.
Everyone should receive equal offer,
equal treatment or opportunity.
So I guess we could take that in two different ways.
One, you could say that that means that it would,
it's okay for them to do this if they spread the opportunity
widely
among those who remain or sort of the opposite.
It it perhaps unfairly excludes
a number of people.
And the next question
was to put it into ethics terms, which many of you had already
done.
And so I just want to highlight a couple of those,
you know, folks talked about equal
opportunity.
And thinking about,
whether it's fair, is it fair to do it or not?
I mean, just look.
Oh, you know, promoting health and safety of the subjects,
right?
By excluding them, we are protecting them.
And so now I'm going to go on
to the question of of those.
And so now I'm going to go on to the question of,
of those who said no.
Other other reasons to say no.
Say that a slightly different way.
Why shouldn't
state X limit enrollment in this way?
Unfair exclusion of the uninsured?
Perhaps inequitable.
It may be seen as discriminatory against those who are uninsured.
Yeah.
Excluding them isn't equitable.
The protocol should account for this.
And make sure that the participants
receive the same care that others
are receiving.
Would limit scientific validity. Yes.
Thank you.
Unfair exclusion without insurance
could be a large demographic and may have other
characteristics.
By excluding them, you may not then be able to
generalize
to the larger population.
Right.
Lots of good words here.
Justice, unfair exclusion, limiting scientific
light, scientific validity,
less representative.
Yeah.
So it it
lots of good lots of good terms here.
Could impact generalizability.
Discriminates against those without insurance.
Great. And so you've already.
I'm really excited. Week six.
You're already. I don't want to ask.
I don't have to ask you to put these into the terms of
someone,
thinking about ethics.
You're already putting them into ethics
terms, which is awesome.
Okay, so what I want to do now is just
cover a couple of recover a couple of the issues
that we've already talked about and then ask.
So we've already,
we've already talked about some of these.
So participants
should be chosen based primarily on the scientific objectives of
the trial.
So issues around scientific validity right.
If someone is medically eligible according to the criteria.
One could say that excluding a particular group,
based on
what we might call a morally irrelevant
characteristic, would be inappropriate.
Participants should be chosen in a way that reduces risks and
enhances
potential benefits both to individuals and society.
Right?
So again, if the if the goal here
is to think about both those who might be eligible,
those who might benefit if enrolled
and those patients in the long run
who may benefit from the contribution
that these individuals make.
We want to think about how well
we identify Phi and consider the risks.
Reduce them as much as you can.
And so one thing that all of you,
many of you noted is like,
what is what does reduce risk mean
in this context?
And it picks up a little on what Joe was mentioning before,
right?
Including someone who is uninsured
may put them at financial risk.
Right.
So when someone is uninsured, that means that they don't
have health insurance, right?
And for those of you who have ever,
you know, visited
an emergency room, for example, when you have health insurance,
you know, you're going to pay
some portion of that bill
if you don't have health insurance.
And and as a side note, right, those rates are negotiated
with the insurance companies, large academic medical centers
or health systems get discounts on that rate.
But if you're a regular old person
who does not have health insurance,
you are paying the full amount of the care provided.
So you may end up paying much more
when you compare
the two costs from someone who's insured
and someone who's not.
That's a general injustice in our system,
but enrolling someone where there's
an expectation that there is going to be
standard of care and someone's going to have to
pay for it,
it's going to be out of pocket for that participant.
So are we putting them at financial risk
as including them
and then we need to balance that along
with the physical, social, emotional
risk of being in the study and then what
the potential benefits are. So
maybe
we would want to engage with the person
in an informed consent conversation about
what might happen if they enroll,
what additional financial,
responsibilities they might have.
What's required by the study is that
this particular baseline care be covered.
And so maybe they want to make a decision
to enroll despite that risk.
Is it appropriate for us, quote unquote,
or for the
clinical study team to make
that decision on behalf of the individual?
And then lastly, as it relates to fair
participant
selection, again, we've talked about this,
the importance of sort of sharing
the risks of burdens and potential benefits of
participation
across all individuals and societal groups as possible.
So we worry about both exclusion and inclusion.
Inclusion as it means someone has an opportunity or a
possibility
of benefiting and exclusion in terms
of whether or not that particular group
is taking on too much of the burden of the
trial
and or won't benefit as a result of their
participation,
or the group from which they come
is less likely to benefit from,
the findings of the study.
We'll talk more about that next week
when we transition
to international issues.
So, Jill mentioned undue inducement.
And so one might be concerned that
if the person who isn't insured
and wants to enroll at one of the sites
where the standard of care
will be covered, if, let me say that
a different way at the other three sites,
they plan to enroll uninsured participants
and the sites will cover
the standard of care costs for those participants.
So the participants in those other
three sites
will not be at financial risk.
This other site wants to exclude anyone who's uninsured
because they don't want to cover that cost.
And so the one worry might be for the folks
who are in those other sites of is providing
covering standard of care for the period
of this trial, which is up to a year.
Is that somehow an undue inducement
for those individuals
and I would argue that it's it's likely not, that it's relatively
modest.
And when we talk about undue inducement
and, and, and Jill mentioned this before,
sometimes we think about it in the,
in the setting of
if you're talking about people who have a condition,
these folks are all at high risk of having long Covid
when there is a potential benefit
for the individuals
who enroll, maybe that's enough as a potential benefit.
And we don't traditionally then pay them for their
participation.
But in this case, there is going to be
for those who are in those other sites,
some financial benefit in covering the standard
of care procedures that they otherwise wouldn't
receive.
Right, because they are uninsured
or they are at risk of long
Covid, they are going to be out in the
community.
Maybe there's something that,
is of undue inducement for them.
But in the context of a trial
for people who may benefit,
we think about undue inducement
as a concern.
But from my perspective,
and we've talked a little about this
before,
undue inducement sort of kicks in
when the benefit that the person may receive,
and in this case, it's a potential benefit from
the,
compound
and some financial benefit of having standard of care
available overwhelms their concerns
about the risk of the intervention
that they may be randomized to.
So another way to say that is that
because the coverage of the standard of
care is so valuable to them,
it would swamp their ability to make
an informed decision about enrollment
because they're going to underestimate
or diminish the potential risk for them.
And from my perspective, I don't think that providing
standard of coverage for standard of care
for those other folks is problematic.
And you guys brought this up categorically
excluding uninsured patients would be a,
I think, a disproportionate response
to undue inducement concerns
and would likely violate that principle above,
that we talked about in terms of fair participant
selection.
So I want
to end with sort of a more meta question
in thinking about clinical trials
and the ethics of clinical trials.
My last question is
if we're thinking about
fairness right.
Is it
so again, just to remind you, we have three sites that are
going
to enroll people who are uninsured
or regardless of their uninsured status,
and another site who wants to exclude them.
Now, is that fair to other participants?
Right.
So another way to think about that is if,
covering that cost
for those who have insurance or charging
insurance is covering the cost
for those who are uninsured, unfair
to the larger participant population
and or is covering it at one site
unfair to the other sites?
And I mentioned these just in the sense that you
you know, generally when we're thinking
about the conduct of clinical trials,
we're thinking,
you know, about the clinical trial itself.
We're thinking about the risk to participants, the benefits to
participants,
making sure
that's balanced, considering informed
consent, increasing the likelihood
that people will understand,
Sometimes we have to
look at how the trial itself is
being designed and how different sites
or different policies or different criteria
might.
Invite.
Disparities or,
inequalities among sites and or participants.
And should it be a goal that everyone is doing the same
thing?
Is that a a reason, a thing for us to
think about
when we're evaluating a clinical trial?
I don't I don't think so.
I'll say from my experience of being on many IRBs,
I'm not sure,
that the average institutional review
board
thinks as much as they should in some cases,
about whether or not some of these arrangements are fair or
not.
And so I'm wondering, I'd like to just open the,
discussion of what do you what do
is whether or
not to include participants who are uninsured,
should we say, in a system
that is already unfair, that it would be inappropriate
to always
or considered to exclude people who are uninsured?
Or do we say, well, given that our system
is by definition unfair, we shouldn't doubly
place a burden on those who are uninsured
and therefore should make sure that we include them as often as
we can.
Does anybody have any sort of opinion
or thoughts about that?
And I'll mention that this is a relatively
this is a unique issue for us, you know, in the United States
in that
it's not the case that everybody has access to health care.
Another way of saying that would be
we don't have to have
this conversation in other settings where
basic health care is provided to everyone.
Right?
It's sort of one way to address the ethical concern is to say,
well,
let's just make sure everybody's insured.
We can't do that.
So then we have to sort of manage, is it okay?
Should we always include or should we exclude?
And what were the justifications for that? Be.
Yeah, I guess I could,
I could see maybe an argument for excluding the uninsured,
like
if the costs of including them were made
for externalized specifically on to the insured participants,
like if they received less compensation
because more money had to,
be given to pay,
for the care of the uninsured.
But even then, it just seems like the
the other side of just of that is just like
you have to exclude a bunch of uninsured
possible participants,
and that just seems like to be sort
of an overriding right issue like that.
It seems particularly indiscriminate,
discriminatory to me.
So that, yeah, I think it would make more sense to just have
like, ideally
there's some sort of institution that can, at least in this case,
you know,
subsidize and pay for that uninsured
medical care and I guess
even more ideally, that we would just have
a sort of different insurance regime
where it's not private in such a way
where some people are uninsured.
Yeah.
So I'll mention and this is, so,
from the perspective
of an academic medical center,
when I was at Hopkins, the School of Medicine
would not routinely
exclude individuals based on their insurance status.
What they would do is once someone is identified as
eligible
and insurance was highlighted as a concern,
they would basically send the person
to the social worker
who is in charge of making sure
that they're receiving all the benefits
that they're eligible for, right?
So someone who's never enrolled in Medicaid
or lives in a state like Maryland,
where there are safety net programs
that individuals can apply for to get their health care
insured.
So that's I think that's one way.
I mean, it doesn't eliminate the
problem, right?
There may be some individuals, right,
who just
are not eligible for they make too much
or they're male or they're not pregnant
or all sorts of reasons.
They may not qualify for any of the public benefits
available to them that they they will be uninsured.
They. Right.
They don't have a job.
Most people get insurance through their jobs.
So that's a way of at least trying to close that gap.
And the other thing,
to think about, I mean, my, my, the most
experience I have
as it relates to inclusion of individual roles
who are uninsured is, you know, earlier in the HIV
epidemic,
where there were trials that were open back
then, you were randomized to a placebo
or an active compound.
You know, as time went by, there would be
many fewer placebo controlled trials,
but still trials that tested the standard
towards the, the new novel thing.
That group by demographically,
were much less likely to be insured
than the average person in terms of their ability
to qualify for disability on Medicare,
their ability to hold down a job, etc..
So, you know, a blanket exclusion of,
of excluding those individuals
meant that they would basically be
without health care for a period of time,
or if they would
extend the time with which they didn't
have access to health care.
So really saw this as an opportunity
to have stable health care,
which again, ethically I find problematic.
But I'm not going to say and therefore
we should exclude them because if that's
the only way to have access to stable
health care, there's a trade off there.
Right.
And, my inclination is to say, if that's the only way
you're going to have access, this seems like a,
you know, given the background conditions,
given the contextual conditions,
it seems, you know, not only reasonable
but important
to facilitate enrollment in clinical trials.
And on the first day of class, I think Christine showed,
there was sort of a series of,
I can't remember the term she used for
er, as I think of clinical research.
And one of those eras was the early,
advocacy for HIV
and the signs that many would hold peer
at the NIH and FDA is, you know, clinical trials is
health care.
Right?
And some people said, well, you know,
that shouldn't be the case, right?
Like, kind of you shouldn't think of clinical trials as
health care.
That's a therapeutic misconception.
But for them, it was literal in the sense
of having access to a clinical trial
means that I might have access to sustainable health care.