If Researchers Find a Tumor Should They Tell You? – Exploring Ethics

If Researchers Find a Tumor Should They Tell You? – Exploring Ethics


(air whooshes) (button clicks)
(computer beeps) (bright digital music) – Tonight’s program, as
for many of our programs, focuses on how technology
is used or applied, but also, in some ways, on the
process of research itself. We’re interested in both, because there are ethical dimensions of both those aspects of what we do. As you, I hope, can all appreciate, in the early stages of research, when you’re still developing something and don’t yet know whether
it works as you intended, and you’re still refining it and learning about the technology you’re working on, it can be one of the most
challenging times, ethically, because you’re moving in a direction where you will know what you’re getting, but you aren’t there yet. So what do you do with uncertain, sometimes highly uncertain, information How should we approach
handling, for example, tentative findings from research
that is not yet finalized, not yet really ready, for
example, clinical application. Imaging studies, where you try and see, in various ways, what’s going on inside the human body are a
really good example of that. You can’t tell what’s in someone’s brain or their heart or their liver, definitely, unless you cut them open and look at it, but that’s not the ideal
option for most of us. You might have to get to that stage, for some things, but not always. So tonight, we have one
of the leading researchers in this domain, Dr. Kathryn
Fowler, Katie Fowler. As a professor in
radiology at UC San Diego, and she and some of her
colleagues have been wrestling with just that question. As they develop a new technology, what should they do
when they see something with a patient who is a
subject in their study? And so she’ll talk about
that and other issues, and we should have an
interesting discussion, tonight. So thank you, Katie. – Thanks. (audience applauds) All right, so, thank you for
the wonderful introduction and the opportunity to speak to you all. I’m glad that you’re
here, tonight, for this. So just by way of
introduction, I am a physician, a radiologist, and a
radiologist is someone who interprets diagnostic imaging. So there are lots of different
kinds of diagnostic imaging, MRI, CT, ultrasound, so we
kind of interpret all of them, and that’s what we do clinically. So if you get a CT scan or an MRI scan, we’re the ones that provide
the read that your surgeon or that your doctor is
gonna use to help treat you. In terms of disclosures
related to this talk, I don’t have any disclosures. And the question tonight, the
question that I was asked is, if researchers find a
tumor, should they tell you, you being the participant
in a research study? By raise of hand, how many
of you have participated in a research study? Okay, how many of you have participated in an imaging research study? Okay, fewer, but, so those
few who have participated, you understand that we typically give you what’s called informed consent. We go through the process with you. We tell you what we’re gonna do. And part of that process, they might say that you’re not gonna be
able to know the results of the test, right, because
it’s still a research test. So we’re gonna talk a little
bit about what that means. So as I mentioned, we have
a lot of imaging that we do, so this is an ultrasound examination. We can scan through in
real-time and see the liver, see the kidneys, see multiple things. Here’s a CT, a CAT scan of the abdomen. This is the liver. Here’s an MRI, and you could see, here, there’s a large lesion within the liver. And then here’s a radiograph where the patient has
taken some oral contrast, and we can see the small
bowel and the colon. So these are all the tests
that we use clinically, and we are fairly confident
in the results of these, but we haven’t always been confident. These also had to be tested and proven before they became part of
common clinical practice. So I wanna walk through
a little bit with you, how do we do that? How do we get a test from
the experimental phase to the point where we’re
gonna be doing it on a patient and using that information
to treat their disease? So things that we’re looking for, we really want the test to be accurate, but if we take a little
bit of a deeper dive, and we talk about what
does accuracy really mean, well, it means that you’re right, right? We want it to be correct. We want to be right, but
there’s a couple pieces of that. There’s something called sensitivity, which really is that we want to identify everyone out
there with the disease. So if we have a test for liver cancer, and we do this test on
all of you, we don’t want to miss anybody in this
group that has liver cancer. We don’t want to have any false negatives. We also have to think about specificity. Specificity means that we
don’t want any false positives, so we don’t want it to
pick up anyone in the group that doesn’t have cancer and
tell us that they have cancer. No one wants a false positive. So we’re trying to balance
sensitivity and specificity. And there’s also this little
thing called repeatability. So that means if I do
this test on you, today, and I get an answer for
each and every one of you, and then assuming nothing has changed, I do this test on you,
15 minutes from now, one day from now, do I get the same answer for each of you or not? So that’s kind of repeatability
or reproducibility. Basically, how reliable is this test? Is it gonna give me the
same answer every time that I administer it? So I somewhat alluded to
this, that we’re trying, it’s always a balance. We would love it if every
test were 100% sensitive and 100% specific. It’s right every time. It’s never wrong. That would be a perfect test. Unfortunately, I can’t think
of a single test out there that we do that is perfect. So we do end up having to balance sensitivity
against specificity. So what exactly does that mean, and why do these two sort
of counter each other? Why can’t they both go
in the same direction? So I wanna introduce the
concept of the ROC curve. How many here have ever heard of this? Okay, everyone from my lab
had better raise their hands. (all laugh) So one way that we can measure and compare different tests is to do something called
an ROC curve analysis. And the history of the ROC
is somewhat interesting. It’s a receiver operator characteristic. So what’s a receiver operator? That was actually a person
who’s listening to radar, in World War II, and trying
to determine if the ping on the radar represents a
Japanese submarine or not. Is it a false positive? Is it a true positive? That’s the history behind this metric that we use in diagnostic imaging. After World War II, it was
picked up in psychology and used for testing, and then
it’s been increasingly used in medical imagine and increasingly
used in all of medicine for testing the accuracy
and comparing the accuracy of different diagnostic
tests that we have. So when we plot this, we look at what the true positives are. This is the same as sensitivity. So the true positives, and we
look at the false positives. This is kind of the inverse
or one minus specificity. And pretty much, if
you had a perfect test, your dot would be way up here, okay, and if you drew a line from here to here, that would basically
be the flip of a coin. 50% of the time, the test is right. 50% of the time, the test is wrong. So you may as well not do the test. You might as well flip a coin. The ROC curve is this
line that we have here. Anything that ends up
above or pretty far below, that flip of the coin is actually
a pretty good test, right, ’cause if it’s way down
here, we can just say, well, maybe we got it wrong. Maybe we just need to
flip what we’re thinking. So this would be a relatively okay test. And we’re gonna talk a
little more about this, as we move forward, but I just want to introduce the concept. We’re not gonna go into any
heavy statistics, tonight. So how accurate does an
imaging test need to be? What about a screening
and surveillance test? How accurate should that be? Well, we don’t necessarily
need it to be highly specific if we’re gonna screen the population. So what is a screening test,
for instance, a mammogram? We want to give everyone
who’s above a certain age, depending on what country
you live in, it’s 40 or 50, we want to screen them for breast cancer, every female in the room. So do we want to miss any cancers? No, we really wanna have high sensitivity. We want to detect all cancers. So if you’re gonna screen a population, you really want to have
a highly sensitive test, and you’re gonna be okay
with some false positives. We’re gonna be okay if we call you back, and we investigate it further,
and it turns out it’s okay. It’s a nothing, but
better safe than sorry. What about a test such as liver MRI? Now this might sound like
a hypothetical situation, but it’s actually not. So we are able, with MRI
and CT, to tell a person if they have liver cancer. We don’t need to biopsy that. And this patient, if
they have liver cancer, could potentially get a
liver transplantation. Other sicker patients, who
don’t have liver cancer, may not get that liver transplantation, because we only have a limited
number of organs out there, and we have a lot of
people with liver failure. So we have to have some way
to distribute those livers in a way that is equitable. So we do give priority for some patients that have cancer, so
if we detect a cancer, and that patient then moves
way up the priority list, gets their liver tomorrow, bypassing all of these
other people without cancer. So tests like that, would we want that to be highly sensitive or highly specific, assuming you can’t have both? I would want that test
to be highly specific. I don’t want anyone
who doesn’t have cancer to bypass other people
who are gonna die waiting for their liver and to
falsely allocate that organ. So we really don’t want false
positives in that scenario. So that test needs to be very specific. How about, tomorrow, you go to the doctor, and you find out that you have cancer, probably gonna happen to most
of us at some point in time, and they want to do an imaging test to tell you how bad is
it, how far has it spread? You want that to be highly sensitive or highly specific? This is a scenario where you kinda wanna
have a balance of both. You want it to give
the maximal sensitivity and specificity that it can, and that’s where we can
go back to our ROC curve, and we can say, based on
what’s called a Youden’s index, we can pick the spot where
we have the highest value for both sensitivity and specificity, and that’s gonna be the test that we want. We want the most accurate test. So now that we’ve introduced a couple of these statistical concepts,
I want to talk a little bit about how we do a research project. And this is pretty much
a very basic outline. We have a new test. In this case, tonight, we’re
talking about an imaging test. We maybe have an old test, or a test that’s standardly
used, all the time. So maybe we want to compare it to a CT, because we know that CT works fairly well. And then we have to compare it against, ’cause if we’re gonna have two tests that give us each answers,
we have to have a truth. We have to have a reference standard to know which test is performing better. Which is actually giving us
the right answer more often? So we need what’s called
a reference standard. Oftentimes, this is a picture of a liver that’s been resected with a big tumor. Oftentimes, that reference
standard is gonna be pathology. That is what we really want. That’s what we would consider
the gold standard, right. That’s where they cut you open. They take a piece of it. They look under the microscope. There’s no higher truth than that, for the most part, in medicine. If we can’t get that, we might say, well, we can just kinda take a composite of what’s going on with you clinically. If whatever this was hasn’t
killed you two years later, it’s probably okay, and so we’ll call that negative or benign. If whatever this is has
gotten bigger or spread, then probably that was a cancer. So we can use other metrics,
but these are less sure. So now I want to present to you, this is, in fact, a hypothetical study. We do a lot of studies at UCSD, but this is not a specific one
that we’re doing right now. It’s just kind of an example to help us walk through this scenario. So we are putting up flyers. We are talking to
clinicians, and we are trying to recruit you for our new research study. We think that our new MRI
method will detect more cancer than the existing tests
that are out there. So forget about your old CT. Forget about whatever
MRI you had yesterday. This new method, we think,
is the next greatest thing. So we’re gonna compare to the old method. Maybe it’s an MRI or CT. It’s whatever you’ve had done in the past, whatever the clinicians may
have ordered on you before, and we’re gonna pick some
form of a reference standard. So if we’re talking about liver cancer, we’re gonna say, okay, we’re
gonna compare to pathology. Maybe that means that you need a biopsy. Maybe that means that
you have surgery done. Whatever it is, we’re gonna
pick a reference standard. And we also, before we
start on any project, we sit down with our statisticians. Now I am not a statistician, but we sit down with our
experts in this field, and we talk about a power analysis. How many patients do we need
to image, assuming this test, we can guess performance about this well, and this test, we think
performs about that well, to be able to tell a
difference between the two? How many patients do we need
to enroll to get to that point? Because we have to prove that they’re not just different by numbers but that they’re statistically,
significantly different, so that the difference
we’re observing is not due to chance alone. So we have to actually have a
lot of planned out in advance. So if we stop halfway through the study, we’re not gonna have the power to show statistical difference
between these two modalities, or if we fail to recruit enough patients, we may not be able to
prove our hypothesis. So we have been successful. We’ve recruited a 50-year-old woman, and she has pancreatic cancer, and she is, in fact,
scheduled for surgery soon. The tests that she’s had done in the clinic showed
no metastatic disease. She’s a good candidate for
surgery, and she’s gonna proceed. But she says, “I come to the
hospital so frequently anyway, “and I may as well help the cause. “I might as well contribute to science, “so I’m gonna enroll in this study.” So she’s gonna participate, and the doctor is gonna
order the standard imaging. We’re gonna compare against it. She understands, because she
signed the informed consent, that the results of our new
tests will not impact her care. We aren’t gonna share her
results in the medical file. The results, because
they’re research only, are gonna stay with us. So her physician may not know. And she won’t know. Well, her imaging test came back positive. Now we’re supposed to enroll 100 patients. She is our first. We see this dark spot I’ve
highlighted with an arrow, and this is something in the liver, and her standard imaging showed nothing. So we think it’s
potentially cancer, right, ’cause we think that our method is better than the standard imaging. So we do have that scenario. Maybe our test is right. Perhaps this is cancer, and
what does that mean for her? Well, that means that if
she has metastatic disease, there’s no point in her having a surgery for her pancreas cancer. She really just needs chemotherapy. That surgery might remove
that pancreas cancer, but if the tumor’s already spread, it’s not going to prolong her life. It’s not going to help
her out in any way really. It’s what we would call
a futile procedure. Well, here’s another scenario. Maybe the test is wrong. Maybe this dark spot in the liver is, in fact, a false positive. Maybe it’s a benign lesion
that we just didn’t see on the regular CT, and,
really, the truth is that she should have that surgery, because this will be
life-saving, life-prolonging to get this cancer out. She has no spread of
disease anywhere else. So we decide to tell her
the results of the test, and she says, “Well, I’d like a biopsy. “I want to find out for sure.” And that sounds reasonable to me. Well, the biopsy is not without risk. The biopsy, even though we
just stick it through the skin, it’s a sharp needle, and
there are things that are in the skin, things in the
liver called blood vessels. They bleed potentially. So now her liver doesn’t look so normal. She’s got a big hematoma, a
big area where she’s bled. And so now, because of this big bleed, she ends up passing away. And the results of this
study, it’s a benign lesion. This is all hypothetical. I’m making this up. (all laugh) But I want you to experience this, because I want you to think about this. What are the possible repercussions of this test being wrong
and us sharing the answers, and that’s really what we’re
here to talk about tonight, are kind of the ethics behind this, the dilemma that we oftentimes
face in research projects, in medical imaging, and
we have to think about. As a physician, we first
want to do no harm. So we really don’t want to do a test that the patient doesn’t need. We don’t want to do a surgery
that the patient doesn’t need. So there are extra risks
to proving something. Even minimal things,
like getting a CT exam, what if you have an
allergy to the contrast? What if you have anaphylaxis,
and your airway closes? There are risks to everything that we do. Also, just the risk of
anxiety, just the knowledge that there could be something
and the fear and the worry that people have to
face when that happens. And, of course, there’s the big risk of making the wrong
decision about the treatment and having a negative
outcome as a result of that. The flip side is that, perhaps, the consequences could be good. Maybe by telling her, we end
up doing the right thing. Perhaps the test was right. We also have to think about, what are the consequences to the research? The research, oftentimes, we do what’s called intention to treat. So we don’t want to alter the
patient’s management based on research test, because
then we don’t know if the outcome is based on what they had or it’s been altered by
what we’ve done to them. So we really wanna have what’s
called intention to treat, where they go on and have the outcome that they would’ve had
irrespective of the research test. So the consequences to
the research are that if it were a therapeutic
trial, and the patient’s on a placebo versus a real drug, if we unbind them, that can have an impact on how they may respond to the treatment. The outcomes can be
changed, if they decide to do something based on the test. And of course, we are held accountable. The University of California
and all universities where they perform research
are held accountable, human subjects’ rights
and what we call an IRB, and we have to submit protocols,
and we are held accountable to stick to the protocols. If we deviate from the
protocols, that could result, potentially, in the
project being shut down, so all the patients who have come before this patient have
sacrificed for nothing. There’s no result that
can happen at that point. And of course, there’s
the risk that we continue, but because of tampering
with what we’re doing, that we can’t prove or
disprove our hypothesis. So with that, I’m gonna, I
think, transition, at this point. – I’m gonna start with a
question that occurred to me as I just thought about the
ethical questions that are here. You’ve even mentioned the
idea that these studies have to be accepted in the
university setting and so on, and that’s handled by the
institutional review board. So the question is, to what extent have institutional
review boards anticipated? As you’re doing studies like this, there’s a risk that you’re
going to see something that’s problematic in your research study. What are you gonna do about it? – Yeah, so we do have
to have a plan in place for how we handle incidental findings. And the imaging that’s performed, for various different reasons. so maybe we’re studying your liver, but there’s something in your bone. There’s something outside of the liver. We have to have a plan in place that someone will review
the imaging for these kinds of findings, and if we know
them to be significant, if it’s clear to us that these
are potentially something that you need intervention,
then we will notify a clinician. If you end up having an aortic dissection or something that’s potentially deadly, that will get transferred to the ordering physician, potentially. And yeah, you have to
have a plan in place, basically to address this. – Yeah, so they are anticipating that. How deeply do they delve into this, because I can imagine,
depending on what you see, depending on the circumstance
of the particular patient, that there are larger or smaller reasons about why you would want
to do something about it? – I would say they don’t
go very deep into this. When we’re doing imaging studies, they kind of classify
different studies based on what they perceive to be the risk. Imaging studies are
classified, for the most part, as a minimal risk to the patient, because we’re not cutting a patient. We’re not giving them medication. We’re just taking pictures. So that is classified as what the IRB would
consider minimal risk. They worry probably more, these days, about the potential threat of
jeopardizing confidentiality, that somehow the results
will be shared outside of where they should be shared. So that is one of the greatest risks that the IRB tends to worry about. – Yeah, so as I’m thinking
about this, it seems to me that the questions are
not just gonna vary based on the circumstances, but
they’re gonna vary based on what the individual would want. So does the IRB or do you, in your plans, adjust what you’re going to do based on individual preferences about whether they would
want to know something? – I have been involved in studies where we have allowed the
option for the imaging study to be interpreted and put
into the medical record, and that’s based on the patient’s
desire for that to happen. We can do that, and that’s an option, but beyond that, the protocols tend not to be very adaptive based
on the patient’s preference. – So what are your thoughts on trying to, how difficult would it be to design your study,
so you somehow include, as part of the informed consent process, options that people can choose,
depending on what you see, or would that be something
that would cause people to not want to be in your study, ’cause they’d worry about
what’s gonna happen? Would there be a negative–
– Well, we try not to hide any risks. (both laugh) So we don’t try to pull the rug over any potential issues like this. The informed consent, sometimes,
I think is too in-depth, because you get handed a packet that’s 10 pages or 20 pages long, and how well can you really read that? And how well can you
really understand that? And who’s gonna take the time? You’re in kind of a hurry. Maybe you’ve had to find
parking at UCSD before. If anyone has ever attempted that, you’re already in a
hurry when you show up. So I think it would be challenging to have too many questions in
the IRB, in the consent form, to address in advance. – Yeah, so what that means is that if we’re designing a
system, we need to design, in a sense, a one-size-fits-all, because we have to come up
with a standard approach. If we’re gonna do that,
what is your sense? I don’t know how much of
an opportunity you’ve had to ask this question or think
about it with individuals, but do most people want
to know whatever you find or most would rather not know, because you don’t know
the significance of it? – It is highly variable. It depends. If you’re studying a
population of patients who are being evaluated
for liver transplantation, it’s a very anxiety-provoking
process for them, and they don’t want anything that’s gonna potentially
jeopardize their chances of getting a transplant. So for them, they may not want to know. But they’re also very
thankful for the system, and they’re oftentimes very
good participants in research. So this is a group that
may not want to know. You might have a different scenario, patients that might want a whole body MRI as part of a research protocol, patients who might be
willing to pay out of pocket for additional imaging, people who are very up to
date on the medical field, very up to date on genetics. They may want to know a lot. It just really depends
on the patient, I think. – So we’ve got an audience here that is very up to date
on things, I’m guessing. So how many of you would want to know? If Dr. Fowler was doing an
imaging research study on you, and she saw something that is abnormal, but she does not yet have proof that it actually is
something that’s problematic, how many of you would want to know? Okay, just out of interest, is there anybody who
would not want to know? (all laugh) Okay, just a very few people. I don’t know whether they
know something the rest of us don’t know or, so that was what. If you’ve done this, and there are a lot of people involved in the studies, so if one of the members of your team let’s on, in the process of capturing the image, oh, I saw something unusual, who’s responsible for making
sure this is done right? Is this ultimately just it’s your fault, because you didn’t train them well enough, or who’s responsible for– – Well, technically, the PI is responsible for every aspect of the study. But we do do extensive training. We have people here tonight,
actually, from our lab who put together some
of the training manuals, who ensure that our technologists
are trained in this way. So we really go to every length possible to make sure that everyone
understands the protocol, everyone understands what their role is and what their responsibilities are, both to the study and the patient. – Okay, great, so we have a vote. I did not know Becca was going
to do it this well for us. She’s actually tallied the votes. (audience laughs) Thank you. And this looks like the
people who raised their hands. Note, seven, actually, we’re explicit that they did not want to know. And so we have a little
bit of information on that. “Just something I would
prefer not to be notified.” And somebody, and we will
not identify the individual, because they are almost as old as me. (audience laughs) “I don’t want to be told at 75.” So they’re saying,
basically, this is a factor that one could imagine. Somebody’d say, there’s a point at which, for whatever reason, I
don’t need to know more, either because of other illness that I’m dealing with, or otherwise. So this raises a question. Some years ago, I was working on a study that had to do with looking at genetic variants people might have, and genes, as you know, even
the best information we have on most genes is that it’s
not anywhere near certain. It’s not the 100% you talked
about, for gold standard. Most, it’s gonna be probabilistic. There is an increased
risk that you will have x, because you have this gene variant. And so as we started thinking about why people would want
to know or not want to know, there were a number of
factors that played in. So do you have kind of a
set of factors in your head that are pretty clear, that are relevant, that people would trade off? I mean, one might be your age,
but are there other factors? – Well, I think a main factor that I personally think about is, is there something you can do about it? So one of the major things
we look at, nowadays, in terms of genetics, one
of the big, hot topics in research for imaging, which I don’t do, because I focus on the liver and the body, but that my neuro-colleagues
do is Alzheimer’s disease. So much is focused on the early detection or the prediction, potentially,
for Alzheimer’s disease. But the question is, if
you know, at the age of 30, that you’re gonna develop
Alzheimer’s disease, what can you do about it? Is there anything you can do now to prevent that from happening later? Or, let’s say, you’re
gonna get it next year, and is there a treatment? Is there anything that we
can do to make you better? Unfortunately, there’s not that much to do for that particular scenario. So I don’t know if I would
personally wanna know, for 30 or 40 years, that I’m
gonna have this happen to me. I think another one is
Huntington’s disease, a very common genetic disorder
that do you want to know that you’re gonna be not
having a normal lifespan, that your children are all, I mean, maybe you do want to know if
you’re gonna have children, whether you’re gonna be able
to pass that on to them. I think that’s an important
concept with genetics, but I think the ability to do something about it, to intervene,
to fix the problem, to me, would be a big factor
in whether or not I would want to know that it’s happening
or that it’s there. – So any thoughts on
the relative importance of the likelihood of
pain or suffering based on what they have, as opposed to something that might not be as significant. I think that gets to
be a little bit harder when you’re talking about
something as non-specific as possibly cancer, for example. – Mm-hmm, well, I think
that if you told me, well, this could be cancer,
and if we take it out today, you’ll live another 50 years,
but it’s gonna hurt a lot. I’d rather have it hurt
a lot than get rid of it. So I think the pain and
suffering is, again, kind of within the context of the futility or non-futility of the procedure. Will it fix the problem or not? I’m willing to potentially
try to, I mean, think about what women go through
every year with mammograms. The false positive rate
is actually quite high. There are a lot of callbacks. And I think women are willing to do that. They’re willing to undergo biopsies. They’re willing to undergo
additional testing, because they really would like to detect that cancer early, if possible. – Yeah, your answers is a reminder that there’s just so many ways that people will deal
with this differently. It might be interesting to get a poll from the audience. How many of you would, if I understood your answer correctly, how many of you would be up
for 50 years more of life, you’re fairly young,
50 more years of life, but pain and suffering
for that period of time? (audience chattering) So some. Some people might say,
absolutely, I want to be around, and even if I’m gonna
have to be suffering, I can deal with that. Some people would say it’s
not just the quantity of life, but if I don’t have that quality, and it might make that answer differently if you’re 75 or 80 years old now, and for how many more
years do you have then if you’re 15 years old, and
then we could ask the question of whether somebody of 15
years old is in a position to make a good judgment about that. To what extent have you, in your plans, ever included the idea that,
yes, we will let people know, but it has to be handled
through their physicians. They would let you know in
advance their physician’s name. Can you give it to their physician? – Yeah, that actually often is the case, because as a radiologist, we tend to be kind of behind the curtain. You guys don’t see us. You see your physician, and then maybe they hand you a report, or maybe you go into MyChart,
and you see a report, but you don’t always meet us. So I think sometimes it’s better coming from someone who knows you, that knows the clinical
context, that can speak to what it means for you
when there’s a finding, because it may mean
something very different, depending on your context,
and I’m not in a position, as a radiologist kind
of behind the scenes, to know all of that context that plays into each individual case. – But is everything you just said true of the research studies,
because I was presuming, if it’s research study, it’s
you that’s actually working with the individual.
– It’s variable. Sometimes, it is us directly. Other times, we have
clinical collaborators, and so we have a clinician
who’s recruiting patients from their clinic and so
then we would kind of defer to them to reach out to the patient. – So then, in that case,
if you found something, you would, and for whatever
reason, you decided to automatically or because
the patient subject had said they want this information,
you would give it to the clinical collaborator
that was provided. okay, good, thanks. So we have a few questions (laughs). – Well, first of all,
Michael, I was gonna say that our sample size here,
and we have a biased, perhaps more educated group. So that’s gonna influence the
answers to your questions. I had a recent situation in which in MyChart at UCSD, I had
gone in for a routine CT, ’cause I’m a cancer
survivor, and it came out where the radiologist had
written probable metastasis, and it was at Christmastime, and my oncologist was out of town, and it had an emotional
upheaval, because I was concerned that there was no one there to
talk to me about the result. So I think this is not just an
exclusive thing for research. Some of us are old
enough that we remember, when we did studies, they
didn’t have ethics committees, and things were done a little
more seat-of-the-pants. But we’ve evolved, perhaps
because of the legalities, that we have a packet of disclosures now. But you mentioned, first,
physician, do no harm, and to me, this is
personal, it is doing harm if there is information out
there, and it is withheld from the patient or the
subject, the research subject. So for them to have
the choice made to them that if information comes out, even if it is perhaps inaccurate, what do we want to do
with that information? If someone else, including the
researcher makes the decision for me, to withhold that information, then I feel that’s an ethical violation, and that’s what I thought was the purpose, even if it was driven by lawsuits, the purpose in having
these disclosures was to give more choice to the
subject and less the person in the leather chair
that makes the decision and give it back to us as a decision. So I’d like to have your comments on that. I don’t think it’s an
all-or-nothing thing, and I think this concept of choice goes beyond just the research,
goes into what do you do with information and how do you
disseminate that information that’s done, even in
a non-research client. – Just to be clear, there’s
two distinct categories here, which I think are really important. One is the clinical, and
maybe you can talk about that, ’cause my presumption is that, in many clinical settings, they
would not allow the patient to see right away the results without, especially if there was
something as dramatic as possible metastasis.
– But MyChart does. (audience laughs) – That you would have
somebody intervening first. That’s the first thing, and
then in a research setting, what is your thought on that
feeling that it’s unethical for you to withhold seeing
something that doesn’t look right in a research study?
– Yeah, so, I’ll talk about the research one first, ’cause I think it’s a
little less controversial, maybe (laughs), but we have to think about how do with generate
evidence and how do we grade that evidence and what is the
strongest level of evidence that we have that
something is good or better than something else. And we tend to think that a
randomized controlled trial, double-blind, is our
best level of evidence. And double-blind, what does that mean? That means that the patient doesn’t know if they’re getting the treatment or not, and the physician doesn’t know if they’re getting the treatment or not. So the precedent for
withholding information for research is firmly established. I’m not saying it’s right,
but it’s firmly established within the construct that we work. And the radiology piece of
it, I showed you some examples that were pretty clearcut. If I saw a mass like
that in someone’s liver, I think I would be fairly
certain that it’s a real finding, still could’ve been benign,
but that it’s a real finding. Sometimes, the results are very uncertain. They’re not necessarily a binary outcome. It’s kind of this continuous variable. And maybe we say, well,
above 70%, it’s positive. Well, what if your test comes back at 68? We don’t know what that means. So I think giving you information, but not having the ability to counsel about what it means, or having the ability to direct you appropriately, can cause more harm, potentially. So I do think it’s a bit
of a double-edged sword. So that’s my response to that. And then the part about MyChart (laughs), we share frustration, the
clinicians do, especially with the radiologists, because
we don’t know, necessarily. We get information from the chart, but we don’t get all the information. We don’t get all the
notes from the oncologist. We don’t get all the notes to say exactly when your last cycle of chemo was, what you had done between
this date and that date. So sometimes, the results that we give, we can say bigger, smaller, new, and then we can say,
well, we were concerned that because this is new,
or because this is bigger, that this may represent
spread of the cancer or worsening of the cancer, but there are also other factors. Some medications cause tumor
to bulge and to kind of swell, and that can look like
progression, and it’s not. So things like that, when
you go in, and you are in the context of the oncologist
or whoever’s treating you, they can take that information
and really give it to you in a way that makes the most sense, for each individual situation. So having that information out there, having access to a bunch of labs, and every lab is flagged as
normal or critical or abnormal, and even my labs, I look
at them, and I’m like, that’s a 0.1 above the normal range. What does this, you know, I
recognize it’s basically normal, but it’s flagged in red,
and that can cause a lot of anxiety, so not having that context and that background to understand
all of the information, I think can be detrimental to
patients and can cause a lot of anxiety, and especially–
(audience chattering) We also share the
frustration of being able to reach the other physicians (laughs). When we have findings, and
we have to call and say that we see something, it
can take an hour or more, or even a day, to get
someone on the phone, to be able to notify them that
this imaging study was done, this finding is here, this
patient needs to be seen by you, or this patient needs to go somewhere, and sometimes we do actually
have to reach out directly to the patient, too, just
to let them know to go to the emergency room or to
make sure they get treated. – Just a quick followup,
’cause there’s part of this that gets back to this
question of false positives and false negatives, and as you described, there is probably no test
that’s gonna be perfect on both of those, and what
this means, in reality, is that if you really didn’t
want to have any mistakes about somebody falsely seeing
something that’s positive, there’s an easy way to guarantee that, and that’s to never say
anything is positive. Doesn’t matter what the test says, you never say, and conversely, if you want to make sure you have no false negatives, you can never say that it isn’t positive. You just always say it’s true, so you won’t have any false negatives. But that isn’t realistic, and what you’re left
with is so much of life, and so much of what you
look at, is not going to be black and white, so on the one hand, you can say, I want to
know what you found, but what did you really find when what if it’s just a
little bit more opacity or something in the image? At what point do you even
say, I think this is abnormal? You have to make a judgment,
and where is that line? – Yeah, for us, it’s all
about communicating degrees of uncertainty and probabilities. And we have devised an
actual classification system for liver cancer. I’m not gonna plug it too much here, but that is an ordinal
scale from a one to a five, five being it is a cancer, one
being it’s definitely benign. So we’re trying to get more
granular and more objective about giving probabilities,
because if you look at the language that
we’ve used historically, concerning for, compatible with, might be, these are very subjective terms that are open to interpretation. – But just to be clear, that
numbering system is using tests that have been validated and are accepted–
– Yes. – As opposed to a research study, using a new imaging technique
where you don’t yet know what that thing means.
– Mm-hmm. – So yeah, good, thanks. Chris, yeah.
– I just wanted to comment on, I’m one of the people that answered no, but it wasn’t because I
was fearful state of mind. It’s really how strongly do you believe in science and statistics
in the development of medical science, going forward. I mean, two good examples
have already been referred to. One, there’s a strong recommendation to discontinue PSA testing,
after a certain age, and the reason is it doesn’t
do anything to extend life. There was another massive study that showed that mammography, scanning for people below 50, doesn’t extend life. People, I think, are maybe not as accepting of scientific reality, and I think that’s an important factor. Going forward, we need
to use more science, and I think a data point
out of a research study is, in my opinion, a dangerous
thing to rely on. You don’t want to start down that road. I mean, we’re in a position where we could have
scientifically rigorous medicine, and I think that’s a better option. I have a question, too, though. Is what you’re doing
in any way related to, I just heard about a controversy about liver biopsies at the VA here. – Oh, no (laughs). – She is not responsible for– (all laugh)
– No, no, but– – Any of what– – What was driving that? Was that a researcher or something? Do you know about it? – I don’t know about that, personally. But it sounds like it’s very interesting. Maybe I should read up on that, but yeah, no, we at UCSD, we’re not
really, the VA is next to us, but they are separate from us. – Yeah, it’s an ethical question
but a very different one than we’re covering tonight. Stephanie. – I can understand the
random double-blind studies, particularly with regard to
investigating new treatments. I would like you to talk
a little bit more, though, about, in particular, imaging studies. When would it be good not to involve the patient in their own care? That is, if there is not a reason not to put an option for the
patient to choose whether or not they want to
know about the results, that very first step, what would that look like,
and why might you do that, and why might you withhold
that from the patient? That’s something that I’m
wrestling with right now. – Yeah, I think it’s a
really good question, and I don’t necessarily have
the perfect answer for this, but I think if you’re
just really uncertain about the imaging tests that you’re doing, and you’re just not sure that it’s better than what they’ve already had done, that potentially you
could be subjecting them to excessive biopsy,
excessive worry and anxiety, and it may all be for nothing. So I think if you’re fairly uncertain, it’s hard when we show images, and I think the imaging studies
we do have gotten so good that it ends up being a little bit more of a black-and-white question
and less of a gray question. But I think it’s easier to comprehend in the context of lab
results that are more of a continuous variable,
a number that’s on a sheet, and where do you fall on that number? So yeah, I would say
that, most of the time, we do have the option for
patients to see the imaging, and the instances where we
don’t would primarily be because they’re also enrolled
in a therapeutic arm, and it’s an imaging
test that’s being done, kind of as part of a larger– – [Stephanie] So it’s in conflict with the therapeutic
randomized double-blind study? – Mm-hmm. – There’s the worry that you, by un-blinding this, in
effect, for the patient, in some way, that you might cause a change in what’s done, but then you, in theory, have this possible
tradeoff in a research study, where you’re doing that,
where you might not, as you described, might not
be telling somebody something that would be helpful to them,
that might change their care. – Now I do wanna clarify, though. Every research study that we do, if we see an incidental
finding, on the research study, we do notify the patients. So we will tell you if
we see a kidney cancer, but we’re doing it for the liver. Usually the results
that we would withhold, and there’s a purpose of
that, would be something that relates to the specific question that we’re asking about the test and the specific organ
of interest, potentially. – That’s an important distinction. Okay, good, thanks, yeah. – I think you indicated
that it’s a dilemma for the radiologist whether to inform the subject, the patient. Why not ask the patient before the study whether he or she would
like to be notified if you find something, and then
when you do find something, give them also the most likely probability of the accuracy of it
and then the patient, the radiologist and the
patient’s physician can then make an informed decision
how to proceed from there, or maybe repeat the
test, six months, again, or year or whatever? – Yeah, I think that’s a very,
very reasonable suggestion, and the idea of adding that to the consent form would
make a lot of sense. We recently had a case,
this is a real thing, not a hypothetical, of
someone who came in, and we did see a spot in the liver, but the test was being done for
something totally different. And it’s so small, and the next step, she, this person, had a lot of allergies, so we couldn’t give contrast. We couldn’t further work it up with that, so the next steps were unclear. So we did sit down and
discuss with the clinician who had a conversation with the patient and came up with a plan,
basically, to address that. So I’d say more often than
not, we do notify people, unless it’s expressly prohibited,
based on the study design, for other reasons. – It seems clearly in the
interest of researchers to have a double-blind study,
because if you start to, this is why you do have those
agreements by the patient to just not know the results. If you keep going in for the
results and notifying patients, that definitely muddies up the results. On the other hand, most people do want to know what’s going on, and if necessary, they would want treatment,
even if it was a small chance that intervention would
be of any help now. So there is that gap. It’s like a conflict between
the patient and the researcher. And the only way, I think, would be if you have very specific criteria under what circumstances
you would intervene and muddy up that research. And one of the worst
things, I think, would be if the researcher has
sort of like an option, 68%, as you said, versus 70, 72. There’s got to be a middle ground, but that middle ground has
to be clearly delineated. – Yeah, and it’s a little clearer when you talk about therapeutic trials. They do have interim analyses, and then they have stop
points, if it’s showing that it’s working or not working. So it’s a little different
than with the imaging studies, but I think that you bring
very, very valid points. – Yeah, so there’s been a
fair bit of conversation and maybe a lot of audience
is advocating for saying, well, it’s information,
and I want the information, whatever information you have,
and I want to just push back on it, a little bit,
because, for two reasons. One is that, as we’ve discussed
already, the information that we’re talking about isn’t
black-and-white information. It’s probabilistic information
that often we don’t know what those probabilities actually are, but we know that it’s not certainties. And the other is that much of
what we’re talking about now, as medicine gets more
and more sophisticated, is beyond even other physicians working in different disciplines, much less the average patient walking in. So I don’t know to what extent, from the radiology end,
you think about this, but just because we’re
giving somebody information does not mean we have really
empowered them in a useful way. We may have just given them an opportunity to roll the dice, for whatever reason. – Yeah, I’d like to take a moment just to give you guys a slightly
different scenario. One scenario we do deal with, and this is a real-life thing. I mentioned earlier about
liver transplantation, and we say that if you
have a certain amount of cancer in your liver, that you should get a liver transplant, that you should potentially
have this life-preserving, life-saving operation. If you have too much
cancer, you shouldn’t. If you don’t have cancer, we
have to wait for your liver to fail, for you to get
to the top of this list. So the criteria, the amount of cancer for determining who is the right candidate to get a liver was defined back in 1994. Imaging has markedly changed since then. We are so much more sensitive,
more specific, so if we said, well, we have a much, much,
much more sensitive test. We can determine more of your cancer. We can see more of it in your liver. And now we don’t think you
should get a transplant. But take a step back. All of these patients do great. Their outcomes are good. So would denying them a transplant, because the imaging has
become more sensitive, be the right answer? Would that be information that
you guys would want to know, that would now preclude you from getting a life-saving procedure, but it is more accurate. We do think it’s more accurate. But you would be saved, and
your outcome would be good, even with the additional tumors. So that’s just another example of where the information may not be in your best interest to know. So it’s just a little different
way of looking at that. – As a lawyer, I’d like to know what lawsuits you are aware
of that’s involved failure to give informed consent. From a legal point of view, we generally are for all
information being made available to a client or to a patient, and that’s why we have
strict informed consent laws. So it strikes me as a little odd that if there’s any availability
to avoid those laws. So do you know of any
lawsuits that have arised? – I’m not aware of any that have arisen from this particular kind of scenario that we have presented. The informed consent is essential, and any patient that we
enroll in a prospective study, we’re gonna get informed consent. And if we’re not gonna
give them the results, that will, in fact, be
in the informed consent, and they’ll read that, I will not have access
to these test results, and they kinda have to be okay with that. I don’t know from the legal
perspective if, after the fact– – [Lawyer] Is that truly informed consent, if they’re not aware what the consequence, so it gets to very complicated
and long discussion. I understand that. – Yeah, I think the idea of informed consent is a
really challenging topic, and whether anyone really ever
can give informed consent, I think is a question. – There’s another aspect to this that we have hinted at, which
is that there’s this risk that the average subject of research and the average patient going in for clinical help is not necessarily savvy about statistics or science. So to what extent do you
feel that there is a gap that we, as a community, need to fill that our general
population, in order to deal with their lives, to deal
with their care, need to understand more, and
we need to do better. To what extent do you feel
we’re off the mark on that? – That’s a tough question. I think it’s hard to know, and
just very, very anecdotally, not scientific at all here, I recently moved from Saint Louis. I was working at Washington University for about 10 years, in
Saint Louis, to UCSD. And I think the population
in San Diego’s very different than the population in
Saint Louis and Missouri. – [Audience Members] Yeah. – So (laughs), hearing some
affirmatives from crowd. So it’s really challenging. The population in Saint Louis tended to be more impoverished,
probably less educated, probably less informed
about what’s going on, in terms of the healthcare system. And I don’t think there
are any programs out there to bridge that gap. Would these programs be something that these particular
individuals would partake in? I don’t know. I think that there’s information out there for those who are interested and who have the resources to get it. I think it’s really hard to reach those without the resources. It’s really hard to reach those who are relatively,
potentially disinterested, too. – Yeah, yeah, so part of
the reason I asked that is because I want to now flip
the question, which is, to what extent are, it
sounds like you aren’t one of those physicians who
tends to be in the room with the patient or a
research subject, even, deciding what to tell
them and how to tell them, but you are providing data that may be part of that conversation. So is it your sense that our medical schools
are doing a good enough job training physicians to
relay that information? It’s often complex and really
important to people’s lives. – I would say that we’re
not doing a good job. I can tell you, not so
much about the research, but we recently undertook this endeavor to create patient-level documents. So the report that goes into
MyChart might be translated into something that could
be actually understood, rather than containing a
bunch of jargon and words that make no sense to someone
who doesn’t have an MD. Even attempting to translate our words into what we think a
patient could understand was a very challenging task. There are patient resource
materials out there. Most medical schools, when you go through, you have the Patient-Doctor-Society
course that you take, and you learn kind of how to be a person, how to be a human, how not to do an exam, how to do an exam, don’t be creepy. (audience laughs)
All of this stuff, you learn, but I think the communication
piece is really challenging, and the farther along you get in your education,
potentially, the more distance between you and the patients that you’re serving, in
terms of what you know and what you understand
versus what they know and what they understand. So I think that gap only gets
worse as you practice longer, and potentially, your
knowledge base increases. – Yeah, thanks, so I think
we’re just about out of time. So I think we’ve better,
at this point, thank you for a really interesting talk. (audience applauds) – Thank you. (gentle music)

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6 thoughts on “If Researchers Find a Tumor Should They Tell You? – Exploring Ethics

  1. Rhetorical question I would hope.

    If their not sure then that is a different matter.

    There are alternate modalities which can be used.

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