Thanks for having me.
I'm excited to be here.
So I'm going to talk about,
the ethics of returning genomic research results.
There are a lot of topics I could talk about in the area
of genetics
and, research ethics and human subjects, research.
But but this is the one that really
has been,
taking the most attention,
over the past decade and a half.
And so I think, I think it has particular
relevance.
I do sometimes say controversial things,
and when I do,
they are my views and my views alone.
I do not represent anyone, of authority
in the federal government.
So let me give you some history, some background,
just so you can see where how we got here.
It was about 2008 that we really had a revolution
in how we did sequencing, the sequencing
technology.
Sometimes people call it next generation
sequencing.
It went from the Human Genome Project,
which cost $3 billion and took a decade
to, to the ability to sequence
a whole human genome pretty quickly in a few days.
For at that point it was about $10,000.
Now it's it's like $1,000.
It's very, very cheap, to, to do sequence
data.
And so this was sort of a paradigmatic
shift in, in, in the way we do things.
And I compared to it's compared here
to Moore's Law, which is the,
is the rule or the, the rule of thumb
about computing technology,
the supercomputers that we all carry around in our
pockets.
The idea there is those double in power
for the same price every 18 months or so.
And so thinking about how much computers
have advanced over the past decade
and a half, you can see that sequencing
technology has been that much more,
impressive.
So it's a powerful research tool,
generates huge amounts of data about an
individual
and really beyond that, which is necessary
to answer most scientific questions.
And when you're generating huge amounts
of data like that, you can obviously find
clinically relevant things in, in, someone's genome.
And so the ethical question broadly stated
is what sort of ethical obligations
do we, as researchers have with regards
to these potentially clinically relevant
findings.
Let me just give you a few terms that I'm going to throw around.
So we're all on the same page. Really.
So sometimes people talk about Gwas
genome wide association studies.
That's when you just take little snips,
little,
slivers of a genome across the entire
thing.
That's not what we're talking about today.
We're talking about, spelling out the entire genome,
whole exome or whole genome sequencing
exons, just the protein coding regions,
the whole genome, genomes, the whole thing
or next generation
sequencing is sort of the the umbrella term.
I will talk about incidental or secondary
findings.
I'll probably use them interchangeably.
Incidental
findings or findings concerning an individual research
participant
with potential health or reproductive importance
discovered
in the course of doing the research,
but not related to the aims of the study.
So there's sort of the we stumble upon them kind of
finding
secondary findings are related, but,
related in the sense
that they're, they have these, these important health
implications
and not related to the aims of the study,
but we,
we intentionally look for them,
actively analyze the genome, looking for
them.
I just explain this primary results,
just just for reference,
are things that are related to the,
the condition under investigation.
So I'm going to primarily be talking about secondary
findings
because we've sort of moved past incidental findings,
things that are important that are,
but unrelated to the research that we're
doing.
So let me give you a warm up.
Okay. Excuse me.
This is actually a real case
that I had.
That was one of the first, ethics consults
that I ran as an attending.
So imagine a clinical researcher studying,
the genetic etiology of breast cancer,
in patients, patients that are presenting for
treatment
at an academic medical center, they get
they've given their clinical consent.
They also get research specific informed consent.
And the team is going to then sequence, their, their,
their genetic material looking from surplus tumor
tissue,
looking for novel BRCA,
variants that might predict disease.
I should say this is an understudied
population of minority population.
So this is, there's there are lots of BRCA variants
that have been identified, but not as many
in this group, at least at that time.
They proposed to de-identify the sequence
data.
They don't plan to return any results,
even though they know they're there.
They're looking for for novel, disease
associated variants.
They know that they're in some percentage of the
population.
They're going to discover already
established BRCA variants that
could be clinically relevant, particularly
for near-term treatment decisions.
Remember, these are women with breast
cancer who are presenting for treatment.
And so knowledge about the their their genetic variants could be
relevant.
And so the question is should these researchers be allowed
to design the study in this way
where they're going to find these things
that are clinically important,
but not give them back to the patients,
to the participants?
The puzzle here,
is there something beneficial
that the team could provide to these participants
that they might not otherwise know
that could be important for their health?
So there's this beneficence argument that
you could make the investigator, however,
can and in fact did say,
you know, we don't have any genetic counselors on staff.
It would cost us a bunch of money
to have to validate these findings,
which we would have to do by law before we can return them.
It would slow us down.
It would actually delay the time to us
finding these novel
BRCA variants that could help thousands of
people.
And so there's this burden on the research enterprise
kind of argument that, is often made.
Also, he made the argument, you know,
or could have made the argument, this isn't my job.
I'm a researcher. I'm not a I'm not providing clinical
care.
If they want to get testing, they can go get testing.
Why should I have to provide this service?
But I think we've moved to a point,
where where those kinds of arguments
that the researcher was
making are no longer, being well received.
So let me give you some early views.
I talked about the stumble strategy
early on.
We're just we weren't actively looking for
things are just stumbling across them.
And doing a case by case analysis.
Would we return results?
Well, we've got to look at all of the
different
contextual features of the situation.
IRBs were very reluctant to return
results,
because they were worried about psychosocial risks.
But today
and this is sort of the top line, thing
I want to
I want to stress genomics is is cheap, it's
ubiquitous.
It's all throughout our research enterprise.
There's a ton of proliferation of expertise and guidance.
We've moved past this idea that it's really
dangerous,
that towards the idea that genomic information
is just another kind of medical
information
and towards the idea that, these psychosocial risks
that we understandably were concerned
about early on.
Really actually,
we've done tons of research and the
the risks seem to be pretty minimal.
Except in some, some isolated,
and very distinct discrete cases.
And so we, we now broadly
have this view that there's some obligation to
look for
and return a defined set of secondary
findings.
But that's just
sort of the top line, the top line, argument.
Like we need to flesh out the contours
of what that obligation might look like.
And one of the ways we need to do
that is to talk about why,
there's a duty to look for genetic research results.
So I've already explained that it's largely a beneficence
based argument, to give people back
important clinical information.
But research isn't clinical care.
I think that's probably something
you guys learned
in the first session of this course.
There are important distinctions,
ethically relevant distinctions between
research and clinical care.
And so researchers can't be on the hook
to give the same kinds
of services, as a doctor would.
A doctor has to do what's best for the patient in front of
them.
A researcher has other obligations
to the research enterprise, to their data,
to whatever generalizable knowledge
they're trying to produce.
And so from my perspective, the best model
for thinking about this and for balancing those
considerations is,
there's a duty to rescue or ancillary care
kind of model,
ancillary care for those of you, if you don't know, is is a is a
role
specific obligation derived from the duty to rescue,
which is a general obligation.
Ancillary care is the idea that researchers sometimes will
have,
participants, groups of participants
in front of them
with known medical needs unrelated
to the research they're doing,
and the researcher could help them meet
those needs at relatively low cost.
A classic cases is if you were going to do
research
in a region where malaria is endemic,
malaria has nothing to do with the research you're doing,
but you could bring along a bunch
of anti-malarial medication at fairly low
cost and give it out to, the people,
and you provide a huge service to them.
But it's unrelated to your, your research.
So that's ancillary care.
I think that's the best model for thinking about returning
genetic
research results.
And really, the the reason I think it's the best
model
is because it specifies conditions
when results should be returned,
i.e. high benefit conditions
where there's low burden to the research,
research team and where there's
the researchers in a sort of unique
opportunity to provide that benefit.
If someone else would be able
to provide the malarial drugs like the researcher doesn't have
to.
But if the researcher is the only one who could, that
helps.
Helps helps limit the cases in which,
ancillary care obligations might be produced.
So it sort of balances the benefit to the participant
and the burden to the research enterprise
in a way that I find,
very attractive in this kind of case.
But it's not a
perfect model, for a number of reasons
I can go into.
But the big one is that it makes return of results
dependent
on researcher expertise and protocol specific resources.
If you're talking about,
burden to the research team as one of the primary
considerations,
if the research team doesn't have
the expertise, doesn't have,
the staff to do this, then they'd say the burden is
too high.
I have no obligation.
And obviously, if we're making return results
dependent
on those kinds of considerations,
that can lead to inefficiencies
and justice concerns, because similarly situated
participants would get different, access
to genetic information based on what
sort of resources or expertise their team
had, which doesn't seem ideal.
And here's a paper we wrote about this.
If people are are interested.
So, I and others have
argued that we should start thinking
about an institutional duty of rescue,
that this obligation shouldn't fall to the individual research
team.
It should fall to the institution
supporting that research team.
And, and there are a number of reasons
why this is,
this is attractive.
The, the main ones are that since
individual researchers
are going to lack the right expertise
if if the institution is providing
those that can sort of centralize
that expertise and those resources,
and do it much more efficiently and effective
and can take this off of the plate of the researchers
and let them focus on their primary research aims.
So it's efficient, it solves justice concerns and,
it allows the researchers to actually do what they're
aiming to do.
So, let me transition here.
I mainly do research,
but sometimes I help, do some policy things too.
And so the NIH intramural IRB,
asked me and my colleague Sarah Hall
to, to chair a working group to come up with, guidance
for how our intramural program should deal with research, the
research,
the genetic research results problem.
And so it's going to build on some of the arguments I just
made.
So this is this is our sort of I can't
call it a policy because that's not fair.
But this is sort of our, our IRBs recommendations or
guidance to,
expectations for for researchers.
So the first argument is it's time for specificity.
We've we've existed in this sort of limbo
for 15 years where we've said,
oh, this is a hard problem.
Here's some interesting ideas, but no one's been willing to
sort of
put pen to paper and say, we need a firm, well-defined
policy.
And I think that's wrong.
I think we're far enough into this debate
that the sort of Wild West, like everyone
doing whatever they want and case by case
analysis, we need to move past that.
I think
it's great to defer to IRBs generally,
but in this case,
we used to have 12 IRBs.
Intramural in the NIH,
and they all had different ways of dealing with this problem.
Now we have a single IRB, so that's better.
But but it would be ideal for institutions
or even the whole research enterprise,
nationally or internationally, to to try to come up to a,
consistent way of dealing with this.
Like I said, existing guidance is very high level and
really,
sometimes avoids making specific or controversial claims, which I
think
we're at this point where we need to start
actually making those, those claims.
So, the IRB asked us to create this policy.
And we argued that there is a broad
but shallow
obligation to return genetic results
generated in research.
Broad in the sense that it applies
to most research protocols,
but shallow in the sense that there's a
very high bar for the kind of information
you have to return.
The American College of
Medical Genetics and Genomics, Acmg,
curates a list that it updates every year or
so.
And right now there are
how many truly how many things on the list?
83 things on the list right now.
So it's a, it's a, it's a very,
very high bar for what, what counts as the kind of thing
that needs to be returned.
Which protocols?
We argued that,
That the deeper the clinical relationship,
the stronger the presumption in favor of
disclosure.
So if you're just doing secondary research
with samples that were collected
elsewhere where you have no relationship
with the participants, there's
that's not a case where you need to return
secondary findings.
If you have a much more clinical like relationship
where you're seeing someone extensively over time, repeat
workups,
maybe you're providing standard of care
as part of the research protocol.
That's the kind of thing would probably would involve returning
secondary findings.
It's a little trickier when you start talking
about,
minimal interactions, like one time interactions.
It's just a one time blood draw.
Maybe not, but if it's a one time or two
time, extensive workup, maybe,
we argued that in this gray area,
at least to start, there's no need to return secondary
findings.
You're welcome to, it'd be.
It'd be lovely, but you don't have to,
but as it becomes easier and easier
as more centralized services
are brought online, the presumption in this category
could evolve, and expand.
A few more things about the IRB expectations.
This is only prospective, older studies,
studies that had already generated
sequence data didn't need to go back
and analyze and return secondary findings.
Only new or new studies or ones that were
being substantially revised.
This is important.
There's no need to generate genomic data
beyond that necessary
to answer the research question.
So if you're only interested in a particular region of the
genome,
and that's all you need to generate
to answer your questions,
there is no obligation to, to do secondary analysis.
You don't have to get
a whole genome sequence if you don't need a whole genome
sequence.
And I think a lot of investigators were
worried that the IRB was going to start
requiring them
to generate all sorts of data that wasn't
even close to what they needed.
But that's, that's that's decidedly not the case.
And as I said, we're distinguishing between
studies
based on the depth of the clinical relationship.
So that's sort of the sketch of the,
the, the, the policy.
What I want to do now,
is to, to run through relatively quickly.
Some related ethical and policy issues
that come up.
If that's the 10,000ft level, these are,
these are some of the more
interesting substantive problems,
some of which.
Well, I have answers for all of them,
some of which people agree with me,
some of which people don't.
But these are the kinds of sort of sticky problems
that we are still working through,
or need to work through.
So, the first one has to do with sequencing data quality.
Quality. This is a more technical one.
But, as I said, researchers are only required to
generate
the sequence data necessary to answer their question.
But more than that, if the kind of quality they
need,
the sort of resolution of the data
that they need,
if the, the research resolution is lower
than perhaps
the clinical resolution, if you can't use the data to,
to if it's not
amenable to, to a secondary analysis,
then that's fine.
You don't have to produce, data
of higher quality or of different type,
to, to do sequence, to do secondary analysis.
The second issue is equity within a protocol.
This is something we talked about a lot in our working
group.
So there's a baseline expectation
that similarly situated
participants would be treated the same,
but it can be acceptable
to treat different groups within a protocol differently.
So, so let's imagine you have a protocol where you've
got,
one group of people who have like an active disease
and they're getting lots of clinical care
and being seen repeatedly.
And you've got another group of people
who are, maybe relatives of that
of of those people who don't have disease,
but maybe have some genetic markers,
and are just being seen once or twice, for a sort of,
control or kind of,
purposes.
It's okay to treat those two groups
differently if we're, if we're focusing
on, clinical relationship, if different groups
within a protocol have, different
clinical relationships with the team,
then then it's okay to give some of them
secondary
findings and others not,
and, and particularly remember, we've got an insular care model
where that one of the, one of the,
considerations is whether the researchers
are in a unique position to give secondary findings.
If participants have already had clinical
sequencing
and already have access to this, this information,
then the researchers shouldn't be the ones to provide
it.
They already have gotten it through
the normal course of their medical care.
And I'll talk about this again later.
There's some end of life situations where
the the beneficence reasons to provide,
this information to people become less salient.
If someone's going to die imminently,
the fact that they have risk
of some sort of cancer
that's going to develop 15 years from
now isn't really relevant to them.
And so it's okay, again, particularly
in the, in the cancer genetics realm, to,
to, to treat people differently for that reason.
But whatever you're going to do, you have to clearly set
expectations
and explain it to people in the protocol
and in the consent form.
Re-analysis, this question comes up a lot.
You've you've got the genome sequenced.
You do the analysis secondary analysis.
You find out that they do or don't have something.
But our knowledge about genetics is constantly evolving.
And the question is whether researchers
have an obligation to go back to
the sequence data they've already obtained and re
analyze
it periodically as the state of genomic
knowledge advances.
In our argument was no,
you can in the research context, research is in clinical care.
So one time secondary analysis is
sufficient.
You're welcome to do more if you have
the resources and the inclination.
But but one time is is enough.
Again clearly explain this in the protocol and the consent.
And and let people know that
sorry that if they want
more clinical genomic testing that's available to them.
But outside of the research context,
negative findings.
So the Acmg list is the one that people use most
often. And,
I don't know the exact number right now,
but estimates are about like 3 or 4% of people will have,
one of those findings when you analyze their genome.
So it's not a huge number, but it's substantial.
But that means that 97, 98, 90, 96,
97% of people
aren't going to have a positive finding for that high bar acmg
list.
So the question is, how do you convey
that negative information to people?
And we argued, in our report that you don't
need to generate and convey a negative findings report.
This is something you do in clinical care.
If you've got clinical genetic testing
and nothing came back,
you'd get a report saying nothing came back.
But we said, that's too much work
for the research enterprise.
Like we don't.
We need to clearly explain to people
that they're only going to be contacted
if they have a positive finding,
and not to assume that they've got a clean bill of
health.
But the, the, the going through the extra
step of generating and conveying
a negative report was, was going to be too
much in the way of resources.
Okay.
Now moving on to some more interesting
sort of normative questions.
What do you do when you've got a,
pro band who's deceased, but the information you've
generated
about their genome could be relevant to,
to their relatives.
And so I have,
I have the paper here.
Yeah. So we wrote a paper.
Side note, this was a paper I wrote.
The former fellow who, if any of you watch
jeopardy bench here, and he's,
he he had a run there for a while
that, that got a lot of attention.
He's the first author on this paper.
So we argued that.
Well, well, obligations to relatives.
Have to be less than the obligations
you have to the problems.
There can be cases where the clinical
information is important enough
that you'd want to try to get it to them.
And so, but we argue that that's a very
high bar, and you should only really be
returning findings when the information has
potential.
Direct and really substantial
implications,
for their health, and the depth of the relationship with the
probe and,
and their family is relevant here as our protocol resources.
So this this is not an expansive
obligation.
And really a reasonable effort standard is sufficient.
But you should, you know, document
what you did.
There's no
no expectation here that you've got to hire
a private investigator and track down a family member,
to, to return information to them.
But if you if you can do so relatively
easily and it's really important,
it's a good thing to do.
Another big question
that we've been struggling with is, is
how to think about settings that have different
standards of care or different, access
to health care resources.
So the question is, is there a duty to return
findings in low
resource settings where benefit will be
substantially less certain.
So, to return to breast cancer case,
if you found out that someone had a BRCA variant,
but they live in a in a country where there are no surgical
suites
that could could treat breast cancer,
should you be returning this information
in that kind of setting?
We call it the Actionability problem. So.
So you only want to return things
one of the, one of the core reasons
we're returning things where we have the
we feel this there's
this idea, there's this obligation
to return secondary findings
so that people can do something about it
so they can improve their health.
But if they can't actually
improve their health because they can't
access resources, what do you do?
Some people have argued that
you should only return things when they're actionable in the
setting,
in the in the community where the person lives.
I disagree.
We wrote another paper about this, but,
I think the argument is
we should default to returning
research results.
Genetic research results in these settings.
For a number of reasons.
I'm happy to get into
if people are interested, but there are a couple of
caveats,
a couple reasons that this case is different.
First, because communities cultures
have different,
relationships with genetic information,
it's it's appropriate to consult with those those
communities
before you start returning the findings
to see whether these are actually wanted.
And two, I'll talk about the right
not to know in a minute, but,
I'll tip my hand.
I'm a right not enough skeptic, but this is one case where,
I think it's important to ask people, individuals,
whether or not
they want to know this information,
because it really if you can't do anything about
it,
that's a case where someone might
or might not want to know.
All right, a few more,
legacy samples.
This is what I call the freezer problem.
So a lot of a lot of protocols have these samples that were
collected
decades ago with sort of minimal informed
consent before
even genomic sequencing was, was, possibility.
And then they want to go back to these samples.
Sometimes they're very valuable
collections,
and sequence them now that the technology exists.
And the question is what do you do about
genomic findings when you sequence them?
Oftentimes they have very general language
in the consent,
like we want to do genetic research
that doesn't mention anything about
sequencing or secondary findings or anything.
Is it ethical to allow researchers to
sequences?
I've got a lot of thoughts on this,
but but,
generally my view is,
that really we should only be thinking
prospectively
that it's fine for people to use these samples,
and sequence them.
But that we shouldn't be returning
incidental findings in these cases.
A lot of times these people are deceased
or they're going to be impossible to find.
And the,
and or they'd be shocked to learn
that these things are being done.
And so, so I think it's okay if you've got consent
to use these samples, it's fine to sequence them.
But that that we don't need to be returning secondary
findings
in these kinds of cases.
There might be some exceptions to that rule where, where it's
sort of
very defined small set of samples.
And we could, we could recontact them.
But generally unless
unless that's the case, I don't think we have to return
findings.
This is another
technical one that I only include
because I'd get a question about it
if I didn't, clear the clinical lab.
Laboratory Improvement act.
This governs how,
sort of quality control in labs.
And there's this rule under clear
that you can't return
information that will be used for clinical
decision
making without having validated it
in a clear, compliant manner.
And so researchers who don't live in the clinical
testing space often say, well, do I have to do that?
And the answer is yes.
I've talked to various lawyers in,
our institution in, in Egypt.
So that's actually CMS, that that governs Clea.
And the answer is yes.
The law doesn't have any wiggle room
for researchers.
If you're going to be giving something back that they could
plausibly
use to actually make decisions, you have to validate it.
But this is getting easier and easier.
And so this really shouldn't be a barrier.
It's not that expensive. And if you plan ahead,
the big thing is you need a second sample to
validate.
So if you have a second sample you can
you can have it in your back
pocket to go, validate before you return results
to participants.
Pediatric findings.
There's a whole I've written a lot about this,
I don't want to get into too much detail here, but
but there's some really interesting
points.
There's a debate about the right to an open
future.
If you're doing pediatric genetic research.
The idea is
you have the right to an open future is an argument that we
should try
to preserve,
a child's ability to decide for themselves
when they're an adult.
As much as possible, and shouldn't be giving them
genetic information that when they're 25,
they might not want to know.
I think there's sort of evolving views on,
this, people are for, for the first,
I don't know, 15 years of the, of the genetic research era.
This was sort of dogma, but now,
the second article is a,
a sort of professional guidance,
a professional society guidance document
I worked on, where we started walking away
from the idea that this right to an open
future
is of, such,
paramount importance and that there can be conditions
under which it's okay to give families access to,
information about their kid
that wouldn't be relevant, until their adult years.
Re consent at the age of majority is
another big one.
You've sequenced someone's genome
when they were a kid.
They turn 18. Now, what do you do?
Do you have to go back to them to get re consent,
to continue using their
samples to return results?
Some colleagues and I have argued
that you don't have to do that.
This is one that where we are very much in the minority.
Generally the policy is that you go to IRB
and they,
they ask for, you ask them for an exception.
So functionally that the cases that you don't have to get re
consent.
But, but we don't for various reasons.
We don't think you actually even need
to take that step.
And misattributed parentage.
This comes up surprisingly frequently.
This is another early case that I had,
in my ethics consultation career, but,
you're doing testing.
You're comparing the genomes of the,
the kid and their parents,
and it's oftentimes you find that
the parents aren't genetically
related to the kid, or the father isn't related to
the kid.
And and what do you do?
Do you disclose that information to people?
I've argued.
No, you you you don't.
But, this is one where I think reasonable people could
disagree.
I've got about ten minutes, so I'm going to move on
to the last big point that I'm going to set up and
then,
leave time for questions if people want to discuss it.
This is something I've looked at quite a bit.
And really a topic that,
that was,
was very controversial and and sort of,
surprised that the vehemence with
which people thought about this topic,
which was surprising to me, which is why I've, I've sort of
chosen
to dive into it and really explore it in a lot
of depth.
Let me give you a case to set this up.
So imagine P is having her genome sequenced.
Could be research, could be clinical care.
Let's say this is research ethics class.
So for research purposes and during the informed consent
process
there's a checkbox that says we might find
important medical information.
One way circuits sequencing your genome.
Would you want to know it yes or no?
She says no.
But during their analysis,
the researchers find evidence of, high genetic
risk for,
non polyp forming colon cancer, which is the kind of thing
where if you don't touch it, it's pretty uniformly fatal.
But if you do know you have genetic risk,
there are, enhanced screening techniques
that you can use and you can catch it
early and it's curable.
And so, like knowing that you have
this genetic risk is really important.
It's it's literally a matter of life and
death.
And so the question is she checked
the no box.
She said she didn't want this kind of secondary information.
Should they disclose the finding?
Should the researchers disclose the finding even though she said
no?
This is sort of the classic case in the right not to know.
Let me just give you a little bit of set up, and then
I'd love
to hear your thoughts on that kind of situation.
Early on in the genomic
findings result, research.
Debate.
This was actually an area where we thought we had
consensus.
We should only be.
The idea was
we should only be returning findings
when they're desired by the participant.
There's an obligation such to accept there's an
obligation.
It's only to offer individual findings
to research subjects
and let them know that they could say
no, solicit
their preference, and only give it to them
when there's some sort of opt in.
When someone has positively indicated
that they want these kinds of findings.
Then the acmg
produced these recommendations or very controversial,
where they, produced this list.
And I should stress the list that I referenced earlier,
these are all things that are associated
with serious disease,
where there's something you can do about it
and where the evidence base is, is relatively strong.
So not Huntington's disease, not Alzheimer's,
where there's nothing you can do about it.
But in these recommendations, they controversially argued
that they should just this should just be the default,
that we should just be returning these things to
people,
and we should not be asking about their preferences.
The world exploded.
It was like every every meeting I went to, every conference I
went to for
for three years, people devolved into shouting matches and their
tears.
It was it was a very dramatic,
eventually you walked back
their recommendations, sort of walked back their
recommendations.
And so there's this debate about the
right now to know proponents argue that,
you know, we we if you return information
without people's,
without people's being,
without their permission, it's a violation of their
autonomy.
And they would say to that first case that I started with
that autonomy concern should take priority over
beneficence.
That person said, no.
If her colon cancer risk,
we shouldn't return that to her.
I'm a skeptic.
I think I said that already.
I can read my whole argument if you want,
but I think it's philosophically shaky
as a concept.
It's actually only the right notes.
And it was only about 25 years old.
And the early literature was what's much less,
strident about the strength of someone's right not to know.
People make
arguments about the right to have the constitutionally
protected
right to refuse medical treatment,
implying a right to refuse information.
I think that's wrong for a variety
of both legal and conceptual reasons.
I've got some empirical data that show how easily, how easy
it is
to shift people's preferences about this,
depending on how you word things.
I think they're concepts like moral
distress and genetic exceptionalism,
that weigh in favor of being skeptical
about the right not to know.
And for a variety of reasons.
I think if we really enshrined as a policy
this strong conception of the right
not to know that would do a lot more harm
than good.
The main argument I would make is from some,
an empirical project I did a few years ago
where we asked people who said no, who checked the no
box.
And we went back to them, give them just a
little bit
more information and said, if you please, make another
decision.
And, about half of them said no a second time
and we call them strong refusers,
but about half of them said yes.
And we call them weak refusals.
So they said no initially and then said yes later.
And the the big thing is
that those strong refusers remembered what they said
before.
They remembered that they said no,
and they said no a second time,
but the weak refuse, or 75% of them
misremembered what they had said.
No, they clearly made a mistake the first time, for most of them
did.
And they thought they had agreed to receive secondary findings.
And so if you enshrine this idea that we have to ask everyone
for,
their view, for their preferences
about whether or not they want to know
secondary findings, some of them are going to make a
mistake.
And this raises, for me at least,
a normative question about whether
we should be constructing right not to know policies to
accommodate
this tiny group of people who are strong
Refusers are really don't want to know,
given the significant harms
to patients or participants that might make a mistake and
mis report
their preferences on a consent form,
or to put a different way,
whose interests are more important
the weak or the strong?
Refusers the people who really don't want
to know,
like imposing information on them
that they might not want, or weak refusers
who are making a mistake and who really do want to know
this
potentially life saving information.
But just to have checked the wrong box.
I'd argue that we should protect the weak
refusers,
but again, reasonable people can disagree.
And this is, Oops, sorry.
I've been playing around with this idea.
We wrote a couple fellows, and I wrote
a law review article a couple of years ago
about the idea of choice masking nudges, the idea that
people
can still have a choice about whether or not to know
information.
But we can sort of hide that choice
from them.
So they'd have to raise their hand.
They'd have to those strong refusers would have
to say,
you know, I don't want to know this
information.
There'd be no question.
There'd be no information in the consent form.
Except for information about how to contact people with
questions.
There'd be no prompting.
I'm attracted to this idea.
I acknowledge that,
in the research ethics and bioethics
community, the idea of choice
masking nudges could be controversial,
depending on the context.
But, I think it's an interesting,
an interesting concept to play with.
All right.
I am nearly out of time. Let me just give you my. Oops,
sorry.
Bottom line, I think that,
we shouldn't explicitly solicit preferences
during the consent process about the right
not to know if people raise their hand
and say, I don't want to know. I think
that's fine, and we can honor that.
But that's the extent of, what I think we need to solicit,
with the exception that when there are people for
whom
the genetic findings might not be clinically
actionable,
it's okay in those cases to solicit
preferences,
but that's an exception, I think, to that to my general
rule.