Genetic Information Disclosure and Whole Genome Sequencing

April 12, 2021

Information

April 7, 2021

ID6422

To CiteDCA Citation Guide

00:04OK, my friends. I think we'll get started.
00:07Welcome to our evening Ethics seminar
00:09series hosted by the Yale School of
00:11Medicine Program for Biomedical Ethics
00:13to tonight's program is hosted by
00:15the Yale Pediatric Ethics Program.
00:17They are very much interrelated,
00:19but tonight we have a very special academic
00:22pediatrician with us before we get to that,
00:25I just want to comment you notice
00:27before perhaps that our upcoming
00:29session is a conversation with
00:31Doctor Professor Tim Snyder.
00:32About his book.
00:33Our malady, which is a very easy
00:35read and very inexpensive.
00:36It's it's either a very small book or along
00:38pamphlet depending on how you look at it,
00:40but it's a it's an excellent read.
00:42I mentioned it's now to the medical
00:44students because some medical
00:45students have copies that are still
00:47available to be picked up that we're
00:48still waiting for you to pick up.
00:50We're looking forward to having
00:52several medical students on
00:53that call coming up in May.
00:57The Tonight speaker is someone
00:58I've known for many years in the
01:01world of pediatric bioethics,
01:02and he's been here once before to speak
01:04and and Doctor Ben will fund is has
01:06had a remarkable career in bioethics.
01:08Believe it or not,
01:10the center of gravity in pediatric ethics,
01:12United States is not New Haven.
01:14You know, we're working on
01:15the center of gravity.
01:161.1 could have argued that it was Wisconsin.
01:19Maybe some would still say so,
01:20but I think it kind of shifted
01:23West from Wisconsin to a place
01:24called the Treuman Katz Center.
01:26I'll talk about that in a moment,
01:28but tonight's speaker to let you
01:30know is Doctor Ben will font.
01:31He is professor of the vision
01:33of bioethics and palliative care
01:34and pulmonary Sleep Medicine in
01:36the Department of Pediatrics at
01:38the University of Washington.
01:39He's an investigator at the Truman Katz
01:42Center for Pediatric Bioethics in Seattle.
01:45Doctor Wilfong attended Muhlenberg College,
01:47Rutgers University of New Jersey
01:49Medical School and completed
01:50his postgraduate training at the
01:52University of Wisconsin and he's
01:54held faculty appointments at the
01:55University of Arizona at the NIH
01:57and at Johns Hopkins University.
02:00Several years ago,
02:01Doctor Wilfong moved out to Seattle,
02:02which is part of the reason why the
02:04center of gravity made that shift,
02:06and he's actually the founding
02:08director of the Truman Katz Center,
02:09and I will tell you that I have
02:11had the pleasure of being out there
02:13a few times for meetings to speak
02:16and to learn an it is.
02:17It's a real pleasure to have the
02:19founding director of that very
02:20important Institute here with us.
02:24Doctor Wilfong's got leadership roles in
02:26various national initiatives, and we're
02:27really not going to get into that now.
02:30But if there's a quite done,
02:32I'll throw in one of his titles or one of
02:34his committees or something if you want,
02:36but it's really not. Essentially,
02:37I want to get to the conversation and
02:39the way the conversation is going to go,
02:41as many of you are familiar with
02:43is Doctor will finally speak for
02:45about 45 minutes, plus or minus.
02:46After that, I will invite you
02:48to submit questions via Q&A,
02:49and then I will be reading them
02:51to Doctor will fund.
02:52So if you have any questions along the way,
02:54that's how we'll do that and we
02:56will have a hard stop at 6:30.
02:58So if you're if I didn't get to your
03:00question, I apologize in advance.
03:02But we'll do the best we can.
03:04I think it's going to be very
03:06interesting night on a problem that I
03:08think is something that's not an easy
03:11question both in the clinical sphere
03:13as well as in the research arena,
03:15and Doctor Wilson has a great deal of
03:17experience and expertise in bioethics in
03:19both the clinical and research arena,
03:21and so with that genetic information
03:23disclosure and whole genome
03:24sequencing welcome Doctor Wilfong.
03:27Thank you, I'm gonna go ahead and
03:30share my screen. To start with.
03:35And.
03:39Oh, I'm kind of in the beginning.
03:41Sorry, OK, here we are.
03:44So first of all,
03:46thank you Mark for that introduction.
03:48It's really a pleasure to be back here,
03:51at least virtually with you in New Haven.
03:54And I look forward to the opportunity
03:57of being back here in person so.
04:00For those of you who are thinking
04:02about my title and wondering
04:03what am I going to talk about,
04:06I'm going to ask you since it's
04:08been a year of Covid Anna year,
04:10I'll probably watching more Netflix
04:11then you've watched in awhile.
04:13I want you to think of what
04:15movie is conjured up by my title.
04:17I want you to think of what movie is sort of
04:20captures your imagination of what I might be.
04:24Talking about today will let
04:26you pause and think about that.
04:29Because of our format,
04:30I can't really hear what your answers are,
04:32but I'm going to assume that.
04:35At least some of you have
04:37thought of this movie.
04:38Gattaca was at 25 years old and
04:40it was really this future where
04:42the world your place in the world
04:45was based upon your DNA.
04:47And of course this is sort of a
04:49futuristic version of the implications
04:51of sequencing of knowledge about genetics.
04:53Being able to predict how people
04:55will behave and how they will do it.
04:58Certainly very sort of a
05:00dystopian vision of the world.
05:03I hope for a variety of reasons that
05:05you'll leave something more optimistic,
05:08and I'm actually going to share
05:11with you another movie that.
05:13I mean partly seriously and partly
05:17jokingly is a better image for what?
05:21Genetics may bring us in the future.
05:23That's the graduate.
05:26Now the reason why I'm using this
05:29movie is because of for those of you.
05:32This is about 50 years old.
05:34For those of you who have not seen it,
05:37there is a very particular
05:39scene where the protagonist,
05:40who's also named Benjamin in this
05:42case played by Dustin Hoffman,
05:44is getting advice from a friend
05:47of his father's about what he
05:49should do for his career.
05:51And he has one word for Benjamin.
05:54And that word is plastics.
05:57This is taking place and you know this.
06:00This film came out in the early 60s.
06:02It's supposed to take place
06:04like in the late 50s.
06:05So clearly plastics at that point
06:07was the future of the world.
06:09So why am I telling you this?
06:11Because I want to share with you
06:13a story of what happened to me
06:15when I was a fellow in Wiscconsin
06:17doing a combined fellowship in
06:19pediatric pulmonologist and.
06:21In bioethics and trying to think
06:23about what I would work on,
06:25and I had some ideas,
06:26but the Phil Farrell,
06:28who was the chair of Pediatrics at that time,
06:31sort of reminiscent of the graduate,
06:33came to me with one word.
06:35Although it's actually maybe
06:36two in this case,
06:37maybe 2 words or three words.
06:39I guess it was began with
06:41the P wasn't plastics,
06:43it was polymerase chain reaction.
06:46This is 1988. He said, you know,
06:49three years ago they developed this new
06:52technique and it's going to change the world.
06:54You need to think about the ethical
06:57implications of molecular biology.
06:59He didn't even use word genetics,
07:01it was microbiology and you should talk
07:03with norm thoughts to his director of your
07:06residency program because he thinks about
07:08the ethical issues of genetic testing.
07:10And by the way,
07:11your appeared pulmonary fellow and
07:13you know any year they're going to
07:15identify the gene for cystic fibrosis.
07:17So you should think about what are the
07:21ethical implications of identifying
07:22the gene for cystic fibrosis so.
07:25I took his advice and as a fellow with Norm,
07:29Fost wrote a paper that came out
07:31about six months after the gene for
07:34cystic fibrosis was identified and
07:36what happened in that six month
07:39period is that a number of companies
07:41started immediately market marketing.
07:45Cystic fibrosis carrier testing to the
07:48general population and the question
07:50that we addressed in article is how
07:52do you think about genetic testing?
07:55But when it becomes technically feasible?
07:57Ian commercially available what process
08:00should be used for deciding whether
08:03or when or how to implement this on a
08:06wide scale basis and what we identified
08:08in this paper is a theme that really
08:11has followed through my entire career.
08:14The notion that.
08:17Genetic testing requires evidence
08:19of benefit and relative evidence
08:21of lack of harm to sort of have
08:23an appropriate balance that it
08:25requires understanding thoughts,
08:27issues of informed consent of education,
08:29quality control,
08:30counseling and that we have to think
08:33about the workforce issues as well,
08:36and so this paper that I worked on in 1990,
08:40the themes of this are still present today
08:43as we think about this as a relates to.
08:47Sequencing,
08:47so I want to begin with this sort of
08:50historical introduction to the issues that
08:53I and how I got interested in this issue.
08:57Uhm?
08:58I've gotta Fast forward.
09:0015 years.
09:0314 years, 2004.
09:04At this point I was working at
09:06the NIH and the Department of
09:08Clinical Bioethics at the NIH.
09:09I was also working with the Human
09:12Genome Research Institute and one
09:13of the things I did while I was
09:15there is that we did research ethics
09:18consultations for researchers who
09:19had questions that they were facing.
09:21There were challenging for the research.
09:23And so the phone Rang and it was
09:27a investigator from the National
09:31Cancer Institute. It wasn't.
09:33At the time I thought myself,
09:36I didn't know that there were
09:37dermatologists working at the NCI.
09:39He then went on and and told me that
09:41he studied the disease called 0 Derma
09:44Pigmentosa which I have to recall.
09:46I had a vague idea of what it was but
09:49couldn't remember although he explained
09:51much more to me on that phone call.
09:54This is a disease genetic disease
09:56that's very rare 100,000 people and
09:58it's caused by defect in the jeans for.
10:00DNA repair,
10:01in fact,
10:02it was through this disease that
10:04the whole mechanisms of DNA repair
10:07were elucidated and the NIH had been
10:10studying this for the last 30 years,
10:12and.
10:15The implication of this disease is that
10:17because of this problem with DNA repair,
10:20children who have this disease are at
10:23a huge increase risk of sun cancer,
10:26so any exposure to UV light
10:28increases their risk of skin cancer.
10:31Some of them also have neurologic
10:33problems as well that develop overtime.
10:36The risk is so great that there's actually
10:39a camp in New York called Camp Sundown
10:41that is for kids with this condition,
10:44so they can actually have a normal
10:47life by having a week of camp that
10:49occurs all night long and they sleep
10:52all day and this is picture in front
10:54of you is an image from that camp.
10:57So why did he call me?
10:59Well, he the investigator was using at
11:02that time the state of the art techniques
11:05which had to do with organizing.
11:08Patients with this condition into
11:10seven different groups based upon a
11:13laboratory analysis of their cells.
11:15That and this was so.
11:17This was not typical genetic testing,
11:20but it was genetic based testing that
11:23really describe these seven different
11:26categories. And these categories.
11:30Might have some ability to predict
11:33how someone is going to do,
11:35but there's a lot of uncertainty about
11:38how meaningful these categories were.
11:40At the NIH,
11:41they were doing a Natural History
11:42study where they were doing research
11:45with patients with this condition.
11:46They were doing these studies,
11:48but they were not routinely disclosing
11:50the results because they were uncertain.
11:52Their ambiguous, but they're using
11:54it for their research because of the.
11:57Community was very small.
12:00People were aware that in other
12:02countries in the UK in particular,
12:05it was actually common to find out as part
12:08what what complementary group you were in.
12:11And so the people.
12:12Then I hate you,
12:14and parts that we want to
12:16find out our results too.
12:17And the investigator contacted me
12:19because he was concerned about this.
12:21He was not sure whether this
12:23was appropriate to do,
12:24and so he really raised us as a
12:27question for me to think about.
12:29And this was the first time I really
12:31thought very specifically about the
12:33question of results disclosure in research,
12:35where there was no prior
12:37expectation of returning results,
12:38but patients were wanting this information.
12:40This resulted.
12:41Overtime and myself working with.
12:43With that,
12:43a fellow at the NIH for Deep Rovinsky
12:46who's now the University Of Montreal?
12:48We wrote a paper about thinking about
12:51the issues of disclosing individual.
12:53Research results to participants and
12:55we try to think through what we are the
12:58criteria for thinking about how to do this.
13:00Because the debate at the time
13:02was really in two directions.
13:031 would say look this is for research
13:06purposes only and therefore there's
13:07no obligation to return any results.
13:09The other view was to say,
13:11you know people if we think about autonomy,
13:14people should have.
13:15Access to information about themselves,
13:17particularly.
13:17There were the ones who
13:19contribute this information,
13:20regardless of its meaning.
13:22So the approach that Guardian I
13:24took was to suggest that in fact rather
13:26than thinking of either a research
13:29focused or an autonomy focused approach,
13:31we should think of we described as a result
13:34focused approach thinking about what the
13:37result itself is to help guide what to do.
13:40Now, the way we thought about the
13:42result focused approach is to think
13:44about 2 broad types of considerations
13:46one had to do with what I will describe
13:49as informational considerations.
13:51The other contextual considerations.
13:53And but informational considerations
13:55include two important concepts one
13:58has to do with analytic validity
14:01and clinical utility.
14:02Analytic validity refers to
14:04whether or not the.
14:06Study the result you get is actually.
14:10A true result.
14:11An analytic validity refers to whether
14:13or not the samples were mixed up.
14:15It has to do with a wide range of
14:17issues that have nothing to do
14:18with the meaning of the result,
14:20but just whether or not the
14:22result is reliably true.
14:23Clinical utility as another critically
14:25important concept is the notion of
14:27what will you do with the information.
14:29How will the information be
14:31useful to drive clinical care?
14:32And you'll see that these notions of
14:34analytic validity and clinical utility
14:36are still relevant when we talk about
14:38issues related to sequencing as well,
14:40and another word for often
14:42used for clinical utilities.
14:43Notion of action ability.
14:44What will you do with the information?
14:47Now I want to distinguish between analytic
14:50validity and what I call clinical validity.
14:52I don't let it validity refers to.
14:56Whether or not the result is real.
14:58Critical validity refers to whether
15:00or not it represents something
15:02about the person or not,
15:03because in fact in many cases
15:05some of the uncertainty,
15:06just as was been described
15:08with zero dermatosis,
15:09that they didn't really know what the.
15:12Clinical validity of the information is,
15:13in other words,
15:14what does it mean to have a certain to be
15:18one of these certain complement groups?
15:20It was unclear now the issue though.
15:23For the people in that study is that
15:25it had personal meaning for them
15:26that it mattered to them to know
15:29what their complement group was,
15:30even if it wasn't clinically valid.
15:32So these notions of clinical validity
15:34and personal and personal meeting
15:36are two other dimensions that are
15:37important as we think about genetic
15:39results and why people may want them,
15:41why clinicians may be reluctant
15:43to return them,
15:44but these were the issues we
15:46have to think about.
15:47The second set of issues are right
15:50described as contextual considerations
15:51and that refers to in a research study
15:54with the relationship might be between
15:56the researcher and the the participants.
15:58Is this a longitudinal study which
16:00was as it was occurring at the NIH?
16:03Is this a biobank study in which
16:05people donated samples that are
16:07being used by people 10 years
16:08later at another institution,
16:10or is there something else like this?
16:13Also,
16:13what is the capacity of the research
16:15team to provide those results?
16:17If we assume that there are certain
16:20expectations regarding consent
16:21counseling, things like that.
16:23What if the researchers are being
16:25what the research is being done in
16:28a laboratory where the folks don't
16:30have that capacity and another
16:33consideration is whether this is
16:35uniquely available only through research,
16:37or whether this is otherwise
16:39easily accessible through any
16:40variety of other approaches,
16:42including Now these days direct
16:45to consumer marketing as well.
16:48So I want to Fast forward now
16:50briefly to a collaboration.
16:52I began a number of years ago
16:54with a bunch of neurologists who
16:56were interested in thinking about
16:58a longitudinal study of chronic
17:01kidney disease in children,
17:02and this study began in 2004,
17:05and we spoke initially like 2018,
17:07and the issue was based upon.
17:11An evolving consensus that we should
17:13only we should not be routinely
17:16disclosing research results,
17:17particularly if there was the lack of
17:20analytic ability and clinical validity,
17:23and therefore is probably appropriate.
17:25Most research to set expectations that
17:27you would not be getting results.
17:31That this group is the dilemma.
17:33Because suddenly as they started
17:34doing more analysis over the years,
17:36they started realizing through one
17:38of the analytics studies they did.
17:41That the diagnosis of the cause of
17:43the contingency that was provided
17:44clinically was not the same as they
17:46found out through their genetic research,
17:49and so it raised question of what
17:51they should do in this circumstance,
17:53particularly when the consent forms
17:54said we will not disclose any results there.
17:57Question is,
17:57what obligations do we have to
17:59think about returning results,
18:01disclosing results when we
18:02told them they wouldn't?
18:03But this might be actually
18:05relevant to their management.
18:06Now I won't be spending a lot of time
18:09getting into how we address this.
18:11Other than simply say one of the
18:13approaches we use and we recommend it was,
18:15well,
18:16talk to the participants and see
18:18in general what they think of this
18:20issue and what advice they would
18:22give and was interesting here is
18:23that there was a range of different
18:25results and some I mentioned to
18:27you that there were some results
18:29related to kidney disease,
18:30but there are other results that were
18:32more ambiguous and more extraneous.
18:33They had that related to the way in
18:36which various results had some impact on.
18:39On IQ at on learning and there
18:41was much more interest among the
18:44participants in those results
18:45related to kidney disease and less
18:48interest in the ones regarding IQ.
18:50So I want to put this into context so you
18:53can be thinking so you have a sense of how.
18:56The research issues have been
18:58evolving over the decades,
18:59and at this point I want to shift gears
19:02a little bit and I'm going to share
19:05with you over the next 20 minutes or so.
19:08Two different projects that I've been
19:11involved with that that involve sequencing.
19:15And the first one is sequencing in
19:17the context of carrier screening.
19:19Now,
19:19if you recall from my first slide,
19:21I showed you from.
19:24From the paper on CF carrier
19:26testing is that one
19:27of the five that was actually
19:29the very first paper ever wrote
19:32was about CF carrier testing.
19:34Over the next decade by as CF terror
19:37testing involved, I became a.
19:39Mixed critic supporter of carrier testing.
19:41I was critical of the enthusiasm to
19:44do without research, but I was in,
19:46but I was supportive of research to learn
19:49how to do CF carrier testing better.
19:52One of the concerns I had about CF carrier
19:55testing as quickly as a pulmonologist
19:57is that it wasn't really clear to me.
20:00What one should do with that information,
20:03particularly as a disease
20:04like cystic fibrosis,
20:05was evolving clinically and I
20:07was worried that when this went,
20:09information about cystic fibrosis would
20:11be presented to individuals who are
20:14seeking carrier testing that both the
20:16obstetricians who might be doing the
20:18testing and the patients might have
20:20no idea of what cystic fibrosis was.
20:22I actually reflected back to when
20:24I was a medical student and I
20:27thought about cystic fibrosis,
20:29multiple sclerosis and muscular dystrophy.
20:31I remember thinking to myself
20:32which one is which.
20:34These are really confusing words and
20:35I can't tell which of these diseases
20:38means which thing 'cause so I worried
20:40very much a cystic fibrosis carrier
20:42testing was actually potentially well.
20:44It could be done well.
20:45It could also be done poorly and
20:47one of the places in my opinion that
20:50in the 1990s was doing it fairly
20:52poorly was Kaiser in California,
20:54where they were routinely offering
20:56this without a whole lot of discussion
20:58without a whole lot of information,
21:00and they demonstrated in that setting.
21:02But there are lots of people who
21:04were interested in it and that
21:06didn't surprise me because.
21:07Yeah,
21:07if you present it in a way that
21:08makes it sound very straightforward,
21:10of course people will say yes.
21:12So why am I telling you that background
21:14now and in relationship to this paper?
21:17Wells,
21:17because the about in 2013 I got a phone
21:20call from a genetic epidemiologist
21:21named Katrina Goddard whom we end up
21:24becoming Kopi eyes with this large
21:26project together that was looking at
21:28doing genomic based carrier testing
21:29for people who are already seeking
21:31cystic fibrosis carrier testing.
21:33The first thing I said to Katrina when
21:36we first spoke on the phone is that,
21:38you know,
21:39Are you sure you want me to work
21:42on this project?
21:43I've been pretty sceptical of.
21:47Cystic fibrosis carrier testing,
21:48particularly Kaiser,
21:48and she continue to work at Kaiser
21:50in an Oregon, which is yeah,
21:52I know that in fact,
21:54that's actually why I want you
21:55to help me with this study.
21:57I want to make sure we're doing
21:59it ethically and I want to do
22:01this the very best way we can.
22:03So we were.
22:04We wrote a grant and we were became part
22:06of what's called the Caesar Consortium,
22:08which stands for the stands for
22:10the clinical sequencing exploratory
22:11Research Consortium,
22:12which were group of studies that
22:13we're trying to address questions of.
22:15How is it that?
22:18Clinical sequencing can be introduced into
22:20clinical practice in a meaningful way.
22:22What is the evidence?
22:23We need to determine how to do this,
22:26and so we wrote a grant regarding how to
22:29do this for cystic for carrier testing
22:32using sequencing and what I want to
22:35do is share with you briefly some.
22:37Some of the key things we learn
22:40from this study and those key points
22:42are based upon this paper that was
22:44published in 2018 and Health Affairs.
22:47Really, the lessons that we
22:48learned from doing this study for
22:50reproductive decision making.
22:52So I briefly describe the study to you
22:54in a couple of this one slide here.
22:58Essentially what happened is that
22:59for people who on their own's
23:01sought out a clinical carrier test
23:03often for cystic fibrosis,
23:05we approach them an and.
23:08To roll on the study and the
23:09way this would work is that if
23:11they agree to be in the study.
23:12Half of them will get sequencing,
23:14other half would just go on with their
23:16usual life other than completing a
23:18bunch of surveys for us as well as us
23:21evaluating their health utilization
23:23within Kaiser over the next year or so.
23:25And So what I want to show you here is
23:28briefly the findings and the important
23:30thing here is that we were not we were.
23:33This is actually important
23:35about about sequencing.
23:36Sequencing doesn't mean
23:37like the movie Gattaca.
23:38You see everything you see
23:40that everything that's there,
23:41you have to make a decision.
23:43What information do you want to look at?
23:46So we had to for this study that was
23:49done in collaboration with GAIL Jarvik
23:51at the University of Washington is
23:54decide how many conditions would we
23:56be looking at for carrier testing.
23:59There were many places that offered
24:01567 someplace as many as 100,
24:03and for this study we ended up
24:06identifying 700 conditions to
24:08offer carrier testing.
24:094 and Additionally,
24:10we also identified people who had
24:12secondary findings in AutoZone.
24:14Dominant conditions that by this
24:16point we're being recommended by
24:18the American College of Medical
24:19Genetics because they were considered
24:21to be highly actionable,
24:23i.e things related to cancer or heart
24:25disease or might be sort of interventions.
24:28So I want to briefly say,
24:30you know,
24:31described to you and have you
24:33see how we approach this and to
24:35show you what our results were.
24:38We actually found that there were
24:40roughly out of the 300 individuals who,
24:42out of 133 women.
24:44Who enrolled in the study?
24:46There were 12 high risk couples
24:48identified who are risk of
24:49having a child with an AutoZone.
24:51Will recessive condition and
24:53three who had excellent conditions
24:55for which they were also risk of
24:57having a child because it only one.
25:00Up only the one that was necessary to
25:02be a carrier for them to have a child.
25:06We also saw several secondary conditions,
25:08including actually 7-7 people had
25:10autosomal dominant conditions.
25:11So gives you some idea of the
25:13scope of what
25:14you can learn from sequencing in the context.
25:18So we're trying to do in this
25:21one slide is summarized.
25:2315 manuscripts into one slide,
25:25so again, we offered 728 condition
25:27gene condition pairs that we
25:30categorized into five categories,
25:31and I'll say more about the
25:34categories on the next slide.
25:36We gave people the option of which
25:38categories they could choose from
25:40and 89% selected all the categories,
25:41although many of them also value
25:42the fact that they're giving
25:44choices between the categories,
25:45and I'll say more about the categories again,
25:47in a few moments.
25:50We also learned that if we
25:52did this that essentially.
25:54Of the individuals who enrolled,
25:5578% had at least one finding,
25:57which meant that if you
25:58test for enough things,
25:59everybody will have a positive result,
26:01and so this clearly has
26:02implications for the workforce
26:04capacity of genetic counselors to
26:05explain what these results mean.
26:06And we found that in our study,
26:08the amount of time it took to
26:10explain this was about 50 minutes,
26:12and for more uncommon conditions
26:14around 8 around 84 minutes.
26:15So if this was to be a nationally,
26:17this will be a huge amount of
26:20effort that would require on the.
26:22On the workforce.
26:24We look carefully at both benefits and harms.
26:27I think one of the things I learned
26:29along time ago was the importance
26:31of trying to evaluate and understand
26:33what the benefits and themes,
26:35benefits and risks are of
26:36a particular invention.
26:37And so we looked to see whether
26:39or not there's any long term
26:41increase in psychosocial outcomes,
26:43such as anxiety,
26:44whether there's any increased
26:45use of mental health services,
26:47and we didn't find any of that.
26:49We did find in a few specific
26:51cases some confusion between
26:52the carrier results and its
26:54implications for chromosome oh.
26:55Conditions which were not included here,
26:57so not not, I would say it's not surprising,
27:01but not everybody fully understood
27:03exactly what these results meant.
27:05Most of the participants did value the
27:07information for reproductive planning
27:09and another benefit is that we did
27:11identify a small number of people who,
27:13unbeknownst to them,
27:14had secondary findings at which
27:16put them at risk of having
27:18medical problems in the future.
27:19So this was also seen by us as
27:21well as by the patients as a
27:24beneficial thing for them to know
27:26their future risk of a condition.
27:29In fact, there was a couple.
27:31There's one instance in particular where a A.
27:34Mother was identified as a carrier
27:37for hemophilia and based upon that
27:39the perinatal management of her
27:40pregnancy was changed so she was
27:42able to deliver in a place that was
27:44prepared for the possibility that she
27:46might have a child with hemophilia,
27:48which in fact when she ended up
27:50having and the child actually ended
27:52up having a subdural hemorrhage
27:54within a couple of days of life.
27:56But because it was known what
27:58the problem was,
27:59they were able to intervene appropriately.
28:03I want to share with you briefly
28:05some information regarding
28:07the five categories that we used to
28:10differentiate the 78728 conditions and
28:12when I also share with you that the process
28:15of coming up with these categories took
28:18us literally about a year and another,
28:20we spent a lot of time thinking how
28:23should we categorize conditions for
28:25CF carrier testing or for carrier
28:27testing so people could make decisions
28:30about which conditions they wanted
28:32and ultimately came up with was.
28:34To make a distinction between 3 broad
28:37categories based upon severity, either
28:39those with a significant shorten lifespan.
28:42Those that were serious.
28:43And those that were mild and you can see here
28:46the definitions of what those categories
28:48were in terms of the level of seriousness.
28:51We spent many iterations
28:52trying to think through this.
28:53How to organize this?
28:54And then of course we had to do
28:56is place all of the categories all
28:58the diseases into these categories.
29:00We also had a category that was
29:02based upon its unpredictability.
29:04So for example,
29:05there are some conditions in which you, they.
29:08Some may be very mild,
29:10some may be very serious,
29:11including life threatening.
29:12So we decided to call that out.
29:15We also called out those conditions
29:17that begin as adults.
29:18So for example,
29:19children who have no symptoms during
29:21childhood but may have problems as adults,
29:23and these could be behavioral
29:25that could be related to hearing
29:27they could be related to medical.
29:29So for example.
29:30We you know I mentioned to you
29:32that some of the secondary findings
29:34related to hereditary cancer syndromes
29:36that occur in adulthood.
29:37So the question was and and the idea
29:39here is that these are categories
29:41that they could be testing for
29:43as well in children,
29:44and also if they chose it.
29:51I was also going to share with you
29:53the actual results that we actually
29:55found in these in these couples,
29:57and So what you can see here is that this is.
30:00On the on the the high risk couples
30:03had the following conditions.
30:07In which two people were carers.
30:09Now I want to point out that the most
30:11common one was hereditary hemochromatosis,
30:13which is a condition that is not routinely
30:15tested for in carrier testing because
30:17of its treat ability and variability.
30:19That was actually the most common one.
30:21The and then you can see some of the
30:24examples of the individual secondary
30:25findings as well that we learn now.
30:28The reason why we chose to do all of
30:30these 'cause we were trying to learn
30:32what the impact of this would be.
30:34And so the idea was to learn.
30:37About what the outcome and impact would be
30:39of testing for all these things, and so,
30:41therefore we decided in a research setting,
30:43it was reasonable to be more broad than
30:45we otherwise might be doing if we were
30:47providing this as a clinical service.
30:49So I want to point out.
30:52To make a couple comments about
30:55the implications of this study.
30:58So one of the things is that even though
31:00we had 300 people who were randomized,
31:02we got limited data on the impact of
31:05couples who had more than a 25% chance
31:07of having a condition that child.
31:09We only had 12 couples.
31:12Also,
31:12because this was on people who initially
31:14sought out on their own carrier testing,
31:16it didn't include people who were
31:18less likely to value carrier testing,
31:20so maybe the results that we found this
31:22was well received really was really
31:24based upon who was selected for this.
31:27So while we learn certain things from it,
31:29our approach was to be very
31:31careful with who we including.
31:33The study might have limited
31:35what we learn from it.
31:38And so I think to me,
31:40one of the challenges
31:41of doing something like.
31:45Critical sequencing are for carrier
31:47testing is how to make the test available
31:49to those who would value it while
31:51avoiding routinely offering in a way
31:53that influences those to get tested who
31:55might otherwise not value it to meet.
31:57This has always been the biggest
31:59challenge of carrier testing,
32:00depending on how we explain it,
32:02how we define it, people might choose
32:04it not because it's really important,
32:06but it seems like it makes sense,
32:08but they don't really quite
32:09know what they're getting.
32:10Into the other hand,
32:12there are some people for whom this is
32:14really meaningful and really want this,
32:16but I think this is really.
32:18Attention. The other thing that this.
32:22Study brought out to me,
32:24which will come back towards the end
32:26is that the value and importance of
32:28carrier testing is because of its
32:30personal value to the individuals
32:32about themselves about their lives,
32:34about their children and how do we think
32:37about this type of reason for doing?
32:40Genetic testing when we have
32:42limited resources,
32:42we're trying to figure out how we
32:44should prioritize our health resource
32:46and you'll see this issue will come up
32:49again as we talk about the next project.
32:52Before we talk about the next project,
32:53I want one of the things I
32:56want to mention to you.
32:57Is that I mentioned you are study was
32:59part of a larger consortium of nine
33:02studies called the Caesar Consortium,
33:03and so one of the things that happens.
33:06Part of this consortium is that we all
33:07get it would get together and write
33:10manuscripts about our collective experience,
33:11and so one of the projects that I got
33:14involved with with with my collaborator Juno.
33:16You as well as a bunch of other folks,
33:19is part of the consortium was to think
33:21about the questions of consent for
33:23clinical sequencing even though all
33:24of our studies were part of research,
33:26the intention was to learn.
33:28How do we do this better clinically?
33:31So a number of us got together
33:32to write a manuscript about the
33:34considerations for clinical sequencing
33:36based upon all of our experience,
33:39and I want to share with you briefly
33:423 tables from that manuscript.
33:44The first is the table of considerations
33:47and the idea of these considerations are
33:49things for people to think about before
33:52they think about the consent process.
33:54The first thing to remember is that
33:57questions that sequence are in the context
33:59of ongoing clinical decision making,
34:01whether it's clinical decision making better,
34:03better pregnancy,
34:04whether that's a clinical decision
34:06making about cancer treatment.
34:07It's about some other question
34:09that's coming up,
34:10which is why clinical sequence is
34:13being introduced. So for example.
34:14Two of the most common reasons
34:16currently why sequencing is done
34:18clinically is in the context of cancer.
34:21An evaluation of cancer treatments.
34:23Another reason is for children
34:24with developmental delay.
34:26An evaluation of developmental delay.
34:27So thinking about the clinical
34:29context may help think about what
34:32information is appropriate to disclose.
34:35The next consideration which will
34:36I'll elaborate on in the next slide,
34:39is that the process needs to be
34:42succinct and responsive to the.
34:44Person's personal situation context,
34:45'cause typically and actually three,
34:47is related to that too, and the converse,
34:49because often typically was done for consent,
34:52is let's make sure we give a lot
34:54of information about genetics.
34:56Alot of technical information,
34:57but that may not be as necessary as knowing
35:00what's important to the individual person.
35:02So the analogy I like to give
35:05is that when we do an MRI.
35:07The consent process does not usually
35:09begin with a conversation about
35:11quantum mechanics and atomic spin,
35:13which is the basis of how MRI is done.
35:17But yet when we do genetic testing,
35:19we often think it's important to know.
35:24What base pairs are,
35:25which is how even the movie
35:27Gattaca got its name,
35:28but are base pairs necessary to think
35:31about the implications of genetic testing?
35:34The other broad set of considerations
35:36for consent that we came up with
35:38collectively was that we have to think
35:41very explicitly about 3 considerations
35:43regarding the results and their implications.
35:45One is to acknowledge the range of results,
35:48including the limitations of interpretations,
35:50so that the expectations are reasonable
35:52and we don't have two high expectations.
35:56And.
35:57One of the other things that
35:59clinicians can facilitate.
36:00The decision making process by
36:01thinking about the potential clinical
36:03and emotional implications for
36:04the individual of those results.
36:05How will it feel to you if you need
36:07to have more doctors appointments?
36:09How will it feel to you to know?
36:12You might have risk of having
36:13a problem later in life,
36:15so at least getting the clinician and
36:17the patient be thinking about that and
36:19also thinking about the implications
36:20of the results for the family,
36:22and being aware that of how they want
36:24to deal with that piece of information.
36:26So the idea.
36:27Was to have these six considerations
36:29in mind when thinking about consent.
36:32I want to really have us focus
36:34on Table 2 for a moment,
36:37which has to do with sample examples
36:39of questions that really relate
36:42back to the second.
36:43But can't relate back to number 2 here,
36:45which is the consent process should
36:47be should be responsive to the
36:49individuals personal situation.
36:50Context. Well, how do you do that?
36:52The idea here is that consent is
36:53not about giving people information,
36:55but actually asking them questions.
36:56Finding out from them information
36:58about themselves to help you decide
36:59what information they need to know.
37:01And so here's a list of what those
37:03questions are fine with their experiences.
37:05Then finally what they think
37:06the benefits are.
37:07Find out questions and concerns they have.
37:09Find out maybe they've already made decision.
37:11One of the things we've learned is that.
37:13Often people when they,
37:14when they are engaged with clinician
37:16or they have an idea of what
37:18they want to do and so starting
37:19all over and acting as though
37:21they have no idea might not
37:22be really reflecting where
37:23they are there at that moment.
37:25But one of the other points and this
37:26is really brought up by many of our
37:28genetic counseling colleagues has
37:30been the notion of trying to get them
37:31to anticipate results and say so.
37:33If you get a result like X, how do you?
37:35What do you think you'll do with that?
37:37And as a way of just getting into sort
37:39of walk through weather what this means
37:41to them and whether they really do order.
37:44Don't want this and why?
37:46I want to.
37:50Also. Share with you that I'm not
37:54gonna go through these in details
37:56because I want to move on to the next
37:58part of the talk is that we went from
38:01those considerations to having twelve
38:02key considerations or key points,
38:03and the idea is that these are the
38:05key points that need to be made
38:07as part of the consent process,
38:09and what I want to do here tonight is not
38:11going through each of these key points,
38:13but point out to you the categories
38:15and sub categories are the first
38:17had to do with information about
38:18the range and limitation of results.
38:20So talking about both the types of
38:22results available and the limitations.
38:23And again, the idea is trying
38:25to make this simple.
38:26Trying to make this sufficiently
38:28straightforward that this can be
38:29communicated by anybody to anybody else.
38:31This does not require some
38:32of the PhD in genetics,
38:34so you could communicate these concepts.
38:36The second is to think through
38:38the implications of the results.
38:40Think about the clinical implications
38:41for the person being tested.
38:43Thinking about the emotional
38:44implications and thinking about the
38:46implications for family members.
38:47So again,
38:48a way of organizing or thinking about
38:50what should be the conversation to
38:53help with the decision making about.
38:55About testing,
38:56so as we were working on our study,
38:59the next thing I want to share with
39:01you is something that happened
39:04happened during our study,
39:06we realized that our approach
39:08to doing carrier testing.
39:10Within Kaiser for people who
39:12are having cystic fibrosis,
39:14carrier testing resulted in people who
39:17were highly educated value genetic
39:19testing a lot and were mostly white
39:22and we started realizing that you know.
39:25If Genic testing is becoming
39:27more widely available,
39:28we need to be thinking more
39:29broadly than the example of CF.
39:31Carrier testing,
39:32and in the context that we did that in.
39:35So we ended up with a number of
39:37collaborators are doing a series
39:39of interviews and focus groups at
39:40safety at hospitals in the in Oregon.
39:43These were.
39:44Federally qualified health centers
39:45where we interviewed both the
39:48clinicians and patients to find
39:49out what they thought of a variety
39:52of genetic services.
39:53The first big point of this paper was
39:55that the conditions were highly sceptical.
39:57The idea of genetics in this setting
39:59and their response was look.
40:00You know,
40:01people have a lot of things to
40:03deal with in their lives.
40:05They have many,
40:06and again typically now this
40:08was done by three years ago.
40:10But now,
40:11with all the focus on systemic
40:13racism and thinking about all the
40:15various ways that people who are
40:17under represented in research are
40:19facing huge number of challenges that
40:21something like genetics seems like
40:23it is like completely unnecessary.
40:25Inappropriate when people are
40:26facing concerns about housing
40:28about addiction about depression,
40:29why would you even think of
40:32offering genetic services?
40:33We talked to the patient so and they were
40:35actually much more open and thought you know,
40:38actually.
40:38In fact we are interested in these types of
40:41services and in fact,
40:42particularly because that these
40:43are being offered to other folks.
40:45We want these two now.
40:46One thing I want to show you
40:48and illustrate for you is how
40:50do we ask people this question?
40:52'cause it's not easy to ask
40:53people about genetics when they
40:55may be less familiar about.
40:56So the approach we took without
40:59with some collaborators.
41:00We created a series of PowerPoint
41:02that that had animated stories and
41:05we actually had three stories.
41:06One was about carrier testing,
41:08one was about genetic testing
41:10for developmental disabilities,
41:11and the third one illustrated here had
41:13to do with hereditary cancer syndromes,
41:16with the notion that somebody who has.
41:20A risk of cancer and the fact that
41:22that risk of cancer in this case.
41:28Suggest that, or in this case she had cancer,
41:31suggested she might be at risk of
41:32having a hereditary cancer syndrome
41:34and perhaps testing might be helpful
41:35to her to know more about what the
41:38implications might be for her daughters.
41:39When we turned out that of
41:42the three examples we gave,
41:44the one that the conditions were at least
41:47plausibly interested in was this one.
41:48An while the patient stress and all of them.
41:51This also resonated the most with them,
41:54in part because they realize
41:55that cancer can affect anybody,
41:57whereas whereas these care,
41:58these rare diseases are pretty
42:00rare and in fact developmental
42:01delays don't happen that often.
42:03But everyone everyone had cancer
42:05somewhere in their families,
42:06so they all could resonate with that.
42:09So. And in fact.
42:13There are guidelines for both
42:15hereditary breast cancer as well As
42:18for what's called Lynch syndrome,
42:20which is actually a hereditary colon cancer,
42:23an individual cancer.
42:25So these are two genetic.
42:30Conditions are hereditary cancer
42:31syndromes for which there are clear
42:33recommendations that if there's a family
42:35history or of a person of a certain age,
42:37it's recommended that testing be done.
42:38So the idea here is not something hey,
42:41do you want this?
42:42Maybe you should think about this,
42:43but you should have this done in the same
42:46way that somebody is having chest pain.
42:48We might say, you know,
42:49we really we really need to do an EKG.
42:52It's not just you want an EKG,
42:54so no, you should have this
42:55and the same idea here is,
42:57yet you should have this done.
43:00So the question then becomes the fact that.
43:06People who are. Low in low income
43:11or underrepresented in research
43:12and clinical care are less likely
43:14to have this type of testing done.
43:16They may. Not have had if they
43:18may not have a family history,
43:20they may not have had a family history taken.
43:22They may not have gotten a referral.
43:24They may not have gotten.
43:26Jenna testing they meant
43:27I've gotten diagnosis,
43:28so we started realizing that
43:29if there was a pop,
43:31if there was a that if we're
43:33looking for an opportunity to do
43:34testing in a way that could have
43:36an impact on health disparities.
43:38That thinking about the issues
43:40of hereditary cancer syndromes
43:41might be very important to do so,
43:43even though I was a pediatrician,
43:45we our country and I decided
43:46to apply for the next round of
43:48funding from the Caesar Consortium,
43:50and it's interesting.
43:51The next round,
43:52five of the six studies were about
43:54Pediatrics and pediatric context,
43:55and ours was the only one.
43:57That was among adults where we
43:59really focused on adults with
44:01hereditary cancer syndromes.
44:02In a primary care setting.
44:05Well I want to show you on this
44:07slide is to acknowledge that there's
44:09a series of decisions that need
44:11to be made regarding doing this,
44:13and it's very complicated to do so.
44:15Part of what our task was and
44:18thinking about our study was saying,
44:20how can we make this process
44:21simpler and less complicated?
44:23To make it more accessible to
44:25people who otherwise might not
44:26have access to these services
44:28where it's hard to be identified,
44:30it's hard to get to come in
44:32to get an evaluation,
44:33and that and the agenda counselor.
44:35And to come back several
44:37times or several visits.
44:38So we one of the things that we
44:40do this in a more simplified
44:42way and still effective.
44:43So the study that we developed
44:45is called the Charm study,
44:47which stands for cancer Health
44:48assessments reaching many.
44:49And the idea here is that this was a
44:52study was done through Kaiser and it
44:54was really done in English and Spanish.
44:57And the team was a very diverse team
44:59from people from Kaiser in Portland,
45:02but also a Denver health,
45:03which is a federally qualified
45:05Health Center in Denver as well as
45:08with collaborators at University of
45:10Washington who did the sequencing
45:12for us as well as collaborators at
45:14a variety of other institutions,
45:16including UCSF as well as Emery
45:18and Dana Farber and RTI,
45:19who helped us with both the risk
45:22assessment evaluation and our study
45:24included a range of both evaluations of of.
45:27Of.
45:28Doing lots of interviews with
45:29participants along the course of
45:31the study to learn about their
45:33experience was like which is part
45:35of which is why we were involved in
45:37Seattle Children's as well because of
45:38our expertise in qualitative research.
45:40The study.
45:41Included individuals aged 18 to 49
45:44who either spoke English or Spanish.
45:47This was done at.
45:50Kaiser in the Portland area,
45:52as well as a Denver health.
45:54We had our different range
45:56of ways of recruiting people,
45:58either through email,
45:59text messages or in person.
46:00In this and similar approaches were
46:02used at Denver Health as well,
46:04including in Denver help.
46:06Also by our direct referrals by
46:08providers for those individuals
46:09who they believe may be at risk
46:12for having hereditary cancer in the
46:14family but had not yet been had an
46:17opportunity for genetic testing.
46:19The main outcome of our study was
46:21to look at the positive findings
46:23related to hereditary breast and
46:25Varian Cancer Orland syndrome,
46:26as well as a range of secondary
46:29outcomes that included both the
46:30number of of other findings but also
46:32included health care utilization.
46:34Their understanding of the care,
46:36their satisfaction, their communication,
46:37and well say the very end.
46:39About personal utility.
46:41The value of this for them.
46:44But I want to share briefly here and
46:46I want to try to be mindful of our
46:48time so we have time for questions
46:50is to suggest that this was a very
46:53complex project where we did. Is.
46:58If you look at this range of services.
47:01We identified 12 different things
47:03that we tried to do differently to
47:05see how well it would work at it,
47:08including how we try to reach people
47:10by identifying people by email or
47:12text which we collected our family
47:14history on a standardized patient,
47:16patient facing tool.
47:18We included people who have limited
47:21information about their families
47:22as a way of being broader.
47:24We provide based on this information
47:26we provided an online risk assessment
47:28and then we also did our pretest
47:30education counseling online as well,
47:32and so the idea here is that the
47:35individuals who were obtaining
47:37this did not actually have to go
47:39into a doctor's office.
47:41Not only one, not only more than once,
47:43but even once all this could be done online,
47:46we also provided halfway through
47:47the study a decision aid to help
47:49people decide whether they did
47:51or didn't want secondary findings
47:52because we found we offer people
47:54the choice of secondary fires.
47:56Almost everybody said yes,
47:57and we worried you know people
47:59saying yes because.
48:00Why not?
48:01It's free, more is better,
48:03so we actually created a decision.
48:05We tried to really slow people down
48:07to think about this more deliberately.
48:10I want to comment about our results.
48:13Disclosure is that we,
48:14for those people had negative results.
48:16We provided that information
48:17initially by phone,
48:18but all my letter for ease of doing this.
48:21The key, if you notice on the side,
48:24there's a couple places where
48:26there are some dice the dice refer
48:28to things that we randomized,
48:30so we did randomize.
48:31People explain this in more detail
48:33in a few moments to two different
48:35approaches to Jenna Counseling.
48:37We also randomized training for
48:39interpreters to see whether or not.
48:41Having trained interpreters would
48:42be helpful to communicating this
48:44information as well,
48:44because this study is still ongoing,
48:46I'm not going to present the
48:48results of this in
48:49the purpose of me and I will
48:51describe some more of the features
48:53of the study in more detail,
48:55but the message I want to
48:58convey is to suggest that.
49:00Studies like this that try to look at
49:02the possibility doing sequencing in
49:04the context of clinical practice is
49:06how we will learn how to do it better
49:09and how we learn how to innovate and
49:11see if we can do this effectively.
49:13So I want to share with you
49:15a few aspects of our study.
49:17One is that our approach to
49:19consent was was done online.
49:20We used a multimedia approach
49:23where we used images.
49:25Actually,
49:25the same colleagues have done
49:26our images for the previous study
49:28of the of the PowerPoints.
49:29Here we use images with very
49:31brief information.
49:31So we really tried to think about.
49:35How to be as concise as possible with
49:37what this test will tell me and one
49:40of the things that I have been a very
49:42big fan of with the concept of consent
49:45is trying to be concise by making
49:47suggestions for what the reasons might be,
49:49why some people may want it,
49:51and why some people may not want it.
49:53And it's a way of both communicating
49:55that there's more than one choice,
49:57but to do it in a way that
49:59makes it fairly so.
50:00Simple to see what those reasons
50:02are rather than thinking there's
50:04a whole litany of things,
50:05but really trying to boil down to
50:07some upsides and some downsides.
50:09The other thing that we did is that we just
50:12about this was done as a research study.
50:14We distinguish between consent for testing
50:16and consent from being in the study,
50:18and so that the first thing we tried
50:20to do is to walk them through whether
50:22or not from their perspective,
50:24genetic testing made sense for them,
50:26and then then say the option for
50:27you is to have it done through
50:29the study or talk to your doctor.
50:32Further,
50:32if you don't want to be in the study
50:34so that the consent was really broken
50:36down into these two different pieces,
50:38I want to say briefly something about.
50:40Our risk assessment approach,
50:42'cause the idea is that people had to.
50:46Normally family history is completed
50:47by a clinician and there are validated
50:50tools for clinicians to use for.
50:54For testing for Lynch syndrome,
50:56for example, so we wanted to do
50:58with working with the collaborative
51:00what's called the Prim. We
51:04modified it so this could be.
51:08Adapted so it will be accessible to
51:10patients who are doing this online,
51:12so we had to really make some changes in it.
51:15We had we simplified the language.
51:17We use less medical terms.
51:19We actually did the calculations for
51:21the participants and we had visual aids
51:23also to help describe what this meant,
51:25and we also have done some of valuations.
51:29Actually forgot that we also do
51:31some evaluations of how well this
51:33modification work and present that today,
51:35but this is actually trying
51:36to work really very well,
51:38so we have been able to create and develop
51:41a tool that people can fill out both
51:43in English and Spanish that describe.
51:46It helps to understand what their actual risk
51:48of having hereditary cancer syndrome are.
51:51They were the most important things we done.
51:54The study is that we wanted to think
51:56through how to do genetic counseling
51:58most effectively and we wanted to
52:00use the information that you saw
52:02in that previous paper regarding
52:04an approach to informed consent.
52:05And we also want to apply that to
52:08Jenna Counseling an for this study.
52:10We actually collaborated with women
52:12in effort PA. Logistic gallon.
52:13Joseph is at University of California
52:15at San Francisco.
52:16Who's been studying Jenna councils for
52:18years and together we collaborate on
52:20creating what we have now described as the.
52:23Aria model of gender counseling
52:25that refers to being accessible,
52:27relational, inclusive, an actionable,
52:29and so the idea is to.
52:32Again,
52:33make the information easy to understand.
52:35Really focus on the relationship between
52:38the clinician and the provider as a way
52:41of helping facilitate understanding,
52:43but more importantly,
52:44helping to facilitate and ensure that
52:47patients understand the actions and
52:49know what steps to do the next time.
52:52So the idea, and So what we did,
52:55we developed a fairly detailed
52:57curriculum to train 2 genetic
53:00counselors to use the Aria model an.
53:02Other two genetic counselors.
53:03Did this get their standard approach
53:05to gender counseling that begins with.
53:06This is the gene.
53:07This is a chromosome.
53:08Let's take your family history.
53:10Let's tell you what your results are.
53:11Let's tell you what it means.
53:13Let's get into the complexity of
53:15this because it's always complicated.
53:17And then will tell you what to do, maybe so.
53:20Again,
53:21here's that.
53:21Here's a very quick example of
53:24the distinction between usual
53:25care and the Aria model.
53:27I'll put the right hand side first.
53:29Again,
53:29this notion that the emphasis and usual
53:32care is on transferred information
53:33is usually built technical language.
53:36It's usually more of a monologue
53:38less participant engagement,
53:39an often it's historically is non directive.
53:41It's like you may want to do this.
53:44You may want to do this.
53:47Whereas the Aria model was
53:49meant to really focus on.
53:51A model of psychosocial
53:53counseling establishing a
53:54relationship with the participant.
53:56You are using direct and simple
53:59language being very clear.
54:01What you should do next.
54:04You you should do X&X as well,
54:07avoiding uncertainty with this.
54:12If more if Mark if you invite
54:14me back in a year from now,
54:16we will tell you the results
54:17of this part of the study.
54:19I don't have those results yet,
54:21but I can share with you because
54:23we've now completed the testing
54:24is I can at least share with you
54:26briefly who enrolled in the study.
54:28We have roughly 800 people
54:29enrolled in the study,
54:30and what I want to share with you
54:33briefly is the fact that we were able to
54:35get a more diverse population that we
54:37had with our first study that roughly,
54:39under under 50% identified as white and
54:41the rest of the patients identified.
54:43Primarily Hispanic,
54:44but in a variety of other groups as well too.
54:47We are also able to try to have
54:49a slightly increased amount in
54:51terms of educational diversity
54:52as well as income diversity.
54:54I without going into the details,
54:57I briefly want to acknowledge for
54:58those of you in the audience that
55:01really are curious about this.
55:03In fact,
55:04we were able to identify through
55:07the charm study.
55:08Quite a number of positive
55:10results of the 800 people we had,
55:13we had 36 people who had positive results
55:15or other pathogenic likely pathogenic.
55:17We also did some additional additional
55:19findings related to other things
55:21that can be found in sequencing.
55:23Again,
55:24want to emphasize that sequencing
55:25doesn't mean you find everything
55:27we had to make decisions.
55:29About 126 genes that we felt were
55:31appropriate to include in our
55:33additional findings panel that
55:34we were going to be reporting.
55:37So anytime you hear the word sequencing.
55:39It doesn't mean everything.
55:41It means a deliberate choice to
55:43include some things and not others.
55:45Last point I'll make before I
55:46end it 'cause Mark said I have
55:48to have up to an hour.
55:50We have time for conversation is
55:51as much about two points to make,
55:53so another 5 minutes I want to at least
55:56acknowledge that we were successful
55:58in reaching people who had a bear
56:00who had a range of barriers to access.
56:03And have it broken down by these.
56:05By these categories I also want to
56:07point out and I thought this was
56:09very important that but we were able.
56:11We also included and we also asked
56:13about ****** or gender minorities,
56:14which are often a group that are
56:16maybe less likely have access to
56:18testing for a variety of reasons.
56:19I also have an complications of what
56:21testing may be important to them
56:23because they may not have access
56:24to family history information if
56:26they have strained relationships.
56:27And this is one of the things that we
56:30learned from interviewing people from
56:32that population who were part of our study.
56:35This side very quickly just suggested
56:37during the course of the study.
56:39Which include the risk assessment tool,
56:41which term eligibility
56:42agreement to be in the study,
56:45returning a saliva kit and then completing
56:47results disclosure as as you can see,
56:50there was a gradual
56:51degradation along the way,
56:52but this was not the study
56:55successfully retained that population
56:57who did have barriers to access
56:59a related to being in the study.
57:03Because I want to skip this slide simply
57:06because we're running short on time.
57:08I just want knowledge we're still doing this.
57:10We are still trying to evaluate potential
57:12risks of this approach in terms of over
57:15testing in terms of the results themselves
57:17in terms of the implications for counselors.
57:19So there's a lot of work we're still doing,
57:22but I want to end with switching
57:25gears slightly and talking about
57:27something else that will.
57:29To give you some final thoughts.
57:32That's right, so here's my final thought.
57:35And it's it's kind of thinking back to.
57:39Related back to.
57:40Gattaca an graduate,
57:42and so I want to end with
57:44something from Winnie the Pooh.
57:46So a number of years ago I wrote an essay
57:48in response to somebody who is looking
57:50at the ethical implications of genome
57:52sequencing in the prenatal context,
57:54and as I thought about that
57:56question of doing prenatal.
57:57Genome sequencing audit infant,
57:59I thought about Winnie the Pooh,
58:02and I thought about that.
58:04The phenotypes of Winnie the Pooh,
58:07and I thought about various characters,
58:09so ER. The person is sceptical.
58:12Jack testing thinks of low in despair.
58:14This is a really bad idea,
58:16and thinking about Tigger
58:18always enthusiastic,
58:18always wanting to say well we can do this.
58:22And it seems to be a lot of enthusiasm.
58:24A lot of the issues in genomics are
58:26the ERS in the triggers and 1:00
58:29remind us of Christopher Robin,
58:30who as the protagonist you know how
58:32to get a commitment to moving forward
58:34to nurturing those relationships with
58:36his friends in the in the in the wood.
58:38But also realizing how to leave
58:40there and had to be very careful
58:42and thoughtful of how he did it.
58:44And of course, poo.
58:46Let's let's find some more honey
58:48who thought this is a bunch of.
58:50Crap bunch of honey.
58:53There's more important things than
58:55worrying about genetic testing.
58:57One of the things that people
58:58worry about with Jenn testing,
59:00particularly for children,
59:01and if we're looking for adult onset disease.
59:03Even for things like BRCA one
59:05or for Lynch syndrome,
59:06is what does that mean for the child?
59:08Whatever child finds out when
59:10they're there for the born,
59:11the parents right before the
59:13board they carry the BRCA 1 gene.
59:15Is that appropriate to do that for a child?
59:18Don't they have a right to an open
59:20future which is a term that's been
59:21used for the last 20 years as
59:23we were thinking about questions
59:24about testing in children?
59:25Since this is a pediatric audience in part,
59:27I want to end on this note.
59:30To suggest is that the right and open
59:32future is a considerations that we
59:34thought about by parents and clinicians,
59:36but perhaps not is a final answer.
59:38But when the parents may want to think
59:41about into account all decisions that
59:43parents make affect their child.
59:45And it really depends on the context
59:47of the request about whether or not
59:49this really will have a meaningful
59:51impact on the future,
59:52in a way that's even concerning.
59:55And even if we cannot predict problems,
59:58it doesn't mean that we should preclude.
01:00:00Decisions by parents based
01:00:03upon their interests.
01:00:04And so, in other words,
01:00:06even if we know that there might
01:00:08be some possible concerns for some
01:00:10parents about doing testing early
01:00:11on for double onset diseases,
01:00:13parents might still make that decision.
01:00:16Now. Why is that so?
01:00:19That maybe is a question
01:00:20maybe for the discussion,
01:00:21but what I want to end on to have you
01:00:24think about that is the following image.
01:00:27For those of you who might know this,
01:00:29I'm not normally would ask this in a talk,
01:00:31but this is actually Christopher Robin.
01:00:34Again,
01:00:35the the instigator for Winnie the Pooh.
01:00:38What you may some of you who are
01:00:39familiar with Christopher Robin in the
01:00:41story of a A Milne is that while this
01:00:43while we're all familiar with Winnie
01:00:45the Pooh stories because we tell it
01:00:47to our children and grandchildren.
01:00:49Christopher Robin was very unhappy
01:00:53with his father because of those
01:00:55stories he felt he was bullied.
01:00:56He felt he was ostracized.
01:00:58He became a strange for him from his
01:01:00father for decades and only really
01:01:02towards the end of his father's life.
01:01:04Did they reconcile?
01:01:06The point of this is that.
01:01:09Amil's decision to tell these
01:01:10stories had an impact on his son.
01:01:12We don't know whether he was aware of that,
01:01:15whether he thought about that,
01:01:17whether they should or shouldn't
01:01:18have influenced his decision.
01:01:19He made,
01:01:20and so I really want to point out
01:01:22in a in a in a very sincere way
01:01:25that while we do think about the
01:01:27the impact on the open future,
01:01:29we don't know what anyone's future will
01:01:32be and what the impact will be and.
01:01:35Just like a million Christopher Robin.
01:01:39It's a journey, so with that we
01:01:41have about 25 minutes for questions,
01:01:43so hopefully I've given you
01:01:45enough things to think about.
01:01:47Emma, stop sharing my screen.
01:01:51Given its last to think about,
01:01:52then thank you very much.
01:01:56Now we'll just take a
01:01:57minute to get your breath.
01:01:58Take a sip of water an I'm gonna
01:02:00invite you folks please to send
01:02:01your questions in via the Q&A
01:02:03and then I will read him to bed.
01:02:10So then the first question that one
01:02:12of the things that occurred to me,
01:02:15kind of in broad strokes, was the.
01:02:19Is the question about.
01:02:22About paternalism,
01:02:22you know you talked about clinical utility.
01:02:24Of course, that for those of us in the
01:02:26room who are who are mainly clinicians,
01:02:28this really hits home.
01:02:29You're going to do this test.
01:02:30What are you going to do
01:02:32with the information?
01:02:33And if parents were to say or
01:02:34a physician says, you know,
01:02:35I just want to know that we
01:02:37greatly in 'cause I'm curious,
01:02:38we greatly discourage him from doing it.
01:02:40Seems like a poor use of resources and some
01:02:42of these tests carry risks for the kid too.
01:02:44But now with the genetic testing
01:02:46and of course the parents.
01:02:47So if a parent said, you know what,
01:02:49I'd really like you to do an
01:02:51X Ray of my kids.
01:02:52Kids need 'cause.
01:02:53I'm curious to see what he looks
01:02:55like when we're not doing that.
01:02:56If there's not clinically indicated,
01:02:58at least we should, right so,
01:02:59so we limit what's available to
01:03:01them and with some of the sequencing
01:03:02that you've referred to.
01:03:04But an awful lot of this information
01:03:05that is kind of optional for parents,
01:03:07this is.
01:03:08There's no.
01:03:08Not necessarily an increased expense,
01:03:09and certainly not an increase risk
01:03:11of doing the test that the risk of
01:03:13the information is certainly one.
01:03:14But I guess what I'm trying to get at is
01:03:16if parents say 'cause you're talking about.
01:03:18Some people just think more is better.
01:03:20So if parents say,
01:03:21yeah, you know,
01:03:22I'd like to know in particular.
01:03:24If somebody in the lab knows I wanna know.
01:03:27Then is it overly paternalistic
01:03:29of us to say now?
01:03:30I know it's really not good for you to know.
01:03:34So that's a great question.
01:03:36Actually, it means that I
01:03:37have to go back to the slide,
01:03:39skipped over towards the end,
01:03:41because that's actually the slides I
01:03:42slipped over that I skipped over briefly.
01:03:45You know, I think.
01:03:46Well, I think there's been a shift.
01:03:48So in other words, I think that.
01:03:51There has been this shift in several ways.
01:03:54One is, I do think just like the example
01:03:56they gave you from zero during pigmentosa,
01:03:59even though from the clinician from
01:04:01the researchers point of view,
01:04:02we don't know what to do with
01:04:05this information.
01:04:05These families who are part
01:04:07of a close knit group.
01:04:09Felt this information was important
01:04:11and they knew its limitations.
01:04:12They knew that it was uncertain what it
01:04:14meant, but they knew other folks had it.
01:04:17They wanted it to,
01:04:18and in fact,
01:04:18part of our conversation with
01:04:20that group resulted in them over
01:04:21the next number of years revising
01:04:23their approaches and getting
01:04:24input from their community.
01:04:25And actually,
01:04:26they made the decision to make
01:04:28that information available with
01:04:29the limitations and with the
01:04:30explanations of what this may
01:04:32mean with the limitations are so.
01:04:33That's an example where,
01:04:34but I think the one of the issues I want.
01:04:37That's a very specific group of
01:04:39people who are high risk of a disease.
01:04:41Where it was meaningful to them to do that,
01:04:44I think other questions come up when
01:04:45we get the thing with the context
01:04:47of when is people are people asking
01:04:49for this information and I want to
01:04:52distinguish between the random.
01:04:53And So what I want to clarify is
01:04:55that right now we're not at a place,
01:04:58nor do I think we are going to place,
01:05:00like Gattaca,
01:05:00where everyone we tested for
01:05:01everything for everything that we've
01:05:03done for reasons for particular
01:05:04reasons may be good reasons,
01:05:05maybe bad reasons,
01:05:05but there are currently based reasons.
01:05:07But the question is,
01:05:08what should the scope be?
01:05:09Once testing is done because
01:05:11with sequencing we have the
01:05:12opportunity to add additional tests,
01:05:14something you know these
01:05:15actionable tests are.
01:05:16These actionable tests include tests that
01:05:18ensure the only develop in adulthood,
01:05:20and that's actually the
01:05:21question you're getting at.
01:05:23Mark and I want to share my screen again.
01:05:27And.
01:05:29See if I can get to this here.
01:05:32I want to go back to one slide but when I.
01:05:36Skipped over right here.
01:05:38So one of the things that.
01:05:41That are the consortium
01:05:42is doing this time around,
01:05:44just like show the consent paper.
01:05:46This is a project.
01:05:47This is the paper that is being led
01:05:50by Amy McGuire and Stephanie Marine
01:05:52at Baylor and a bunch of other Anna
01:05:55Bunch of other folks in which there
01:05:58we are trying to collectively.
01:06:00Articulate the range of perceived
01:06:02utility from the point of view of
01:06:04patients for genetics and the point
01:06:06of this model is to suggest that
01:06:09there are a range of utilities
01:06:11and that we can distinguish,
01:06:12and we spent a lot of time just like
01:06:15the issue of categories that describe
01:06:17for the for the next Gen paper,
01:06:20the categories of diseases here,
01:06:22which categories of utility,
01:06:23and we did interviews with participants
01:06:26in the various Caesar studies about
01:06:28their experience with genetic testing
01:06:30in order to come up with these domains.
01:06:32Of perceived utility.
01:06:33One of those domains is clinical.
01:06:36The way in which the information will you
01:06:38know either established new diagnosis,
01:06:40informed clinical management may result
01:06:41in referral to a trial may allow screening.
01:06:44These are clinical outcomes
01:06:45and clinical values,
01:06:46but we also learned was that
01:06:48there were range of other values,
01:06:50and some of these are positive.
01:06:52Some of these are negative.
01:06:53We look at the emotional one at the bottom.
01:06:56You can identify the potential
01:06:57for adverse feelings as well as
01:06:59positive feelings,
01:07:00and I think the point here is simply
01:07:02acknowledge that one of the impacts of
01:07:05testing with positive thinking can be.
01:07:06An emotional impact and.
01:07:09Additionally,
01:07:10there can be behavioral impacts, and again,
01:07:12here we're talking about behavioral impacts.
01:07:14They're not the same as clinical,
01:07:16but might have meaning,
01:07:18and here we include things like
01:07:19changing health habits,
01:07:21future planning,
01:07:21whether it's for financial or career choices,
01:07:24parental decision making,
01:07:25reproductive decision making,
01:07:26influence coverage.
01:07:27These are things that people
01:07:28might do with the information on
01:07:30the issue of curiosity.
01:07:32I think we would describe as cognitive is.
01:07:35In other words,
01:07:36it might impact their understanding.
01:07:37It might be satisfying their curiosity.
01:07:41And it may be relevant to the how they view
01:07:43the information related to overall health.
01:07:46And finally, there's a social
01:07:47impact of of testing that may.
01:07:49So, for example,
01:07:50one of the things that we learned
01:07:52and it not only in this state,
01:07:54but previous studies,
01:07:55is that often having a genic diagnosis
01:07:58ocular for children for children,
01:07:59parents with rare diseases,
01:08:00is a way of being part of
01:08:03a social support network.
01:08:04Its way of having access to social services.
01:08:06When I was at the NIH working
01:08:08in the Genome Institute,
01:08:10they would see patients.
01:08:11With rare diseases and it turned
01:08:13out one of the most stressful
01:08:15things when a family would come
01:08:17in with a perceived rare disease
01:08:18in which the Jess would say,
01:08:20hey,
01:08:20we've got some good news for you.
01:08:22You don't have this terrible disease
01:08:24you thought you had is actually this,
01:08:26or we don't know what it is,
01:08:28but it's not that and people were
01:08:30often unhappy to be told they
01:08:32were no longer part of the group,
01:08:34and so the point here Mark
01:08:36is that is to suggest that.
01:08:39There is a range of value of this.
01:08:41One of the other things that
01:08:43the Caesar consortium is doing
01:08:45is interacting with payers.
01:08:46People who provide the coverage
01:08:48for testing and the try to at least
01:08:51have on the agenda that some of the
01:08:53value of testing for individuals
01:08:55is not simply only clinical,
01:08:56but it's these other ranges too.
01:08:58And the question is, you know,
01:09:00where do we fit this in two questions
01:09:02about resource prioritization?
01:09:04And I don't want to.
01:09:05I can't answer that for sure,
01:09:07but I think the idea is to at least
01:09:10suggest it ought to be on the table,
01:09:13and I wouldn't suggest that
01:09:15testing simply for that.
01:09:16That cognitive utilities have
01:09:18no meaning for an individual,
01:09:20and I think the best example of that,
01:09:23frankly, is. Yeah, I do have a diagnosis.
01:09:26Is that really?
01:09:27If it's a diagnosis that we
01:09:28can't do anything back,
01:09:29we can simply say you've
01:09:31got a rare condition.
01:09:32Would it be appropriate for a
01:09:35insurance insurance company?
01:09:36Say we don't?
01:09:40We shouldn't pay for that.
01:09:41Do anything with.
01:09:42We usually will say.
01:09:44You know that that may be
01:09:45valuable to the person,
01:09:46and therefore it's worth doing.
01:09:48So I think the biggest,
01:09:49biggest reasons for
01:09:50clinical sequencing, but
01:09:50maybe not sometimes these tests
01:09:52are not to satisfy the curiosity
01:09:53of the patient or the parent,
01:09:55but the curiosity of the physician
01:09:56where this isn't actually going to
01:09:58help us manage this patient at all,
01:10:00but it'll it'll.
01:10:00Best Buy sometimes our curiosity and
01:10:02that that's a whole separate issue,
01:10:04and as far as the the the the,
01:10:06the emotional outcomes or benefits of this.
01:10:08I mean, I'd say I remember that when
01:10:09the first time with my second child
01:10:11was our first prenatal ultrasound,
01:10:13and when the afterwards they said
01:10:14would you like to know the ***?
01:10:16And I recall exactly I knew
01:10:18exactly what I was thinking and
01:10:20I said to my wife and said,
01:10:21you know, I said I didn't really
01:10:23want to know it necessarily,
01:10:24but I'm looking at this tech
01:10:26and I'm thinking, well,
01:10:27if you know what I want to know,
01:10:29if you know what I mean.
01:10:31If somebody else is so
01:10:32you about other people,
01:10:33but it could be the same with the
01:10:35IT could potentially be the same
01:10:36with some people to say to their to
01:10:38the researcher or the clinician.
01:10:40Well, if you're aware of something like this,
01:10:42I want to be aware of if nobody knows
01:10:44if it's, you know if it's in the dark.
01:10:46We've never looked at that.
01:10:47We've never examined that.
01:10:48That's a different feeling,
01:10:49potentially for the patient
01:10:51or the research subject then.
01:10:53Then then you know somebody else knows
01:10:56it and excuse me, sorry bout that.
01:11:04Sorry about what happened.
01:11:05I keep hitting this pilot is
01:11:07not working, I know but you know so let
01:11:09me answer your second question first.
01:11:11I gotta get to the next
01:11:13question here Ben. OK,
01:11:15we've got a couple of questions to get to.
01:11:17What have you learned from the
01:11:19studies like charm that would inform
01:11:21the argument for doing genetic
01:11:22screening as part of the newborn
01:11:24congenital disease screening programs?
01:11:27Oh that's oh,
01:11:28thank you for asking that question.
01:11:30I'm, you know. First of all,
01:11:33I think there's different ways of
01:11:35thinking about newborn screening and
01:11:37thinking about sequencing and the role
01:11:39of sequencing with the newborn screening.
01:11:42And So what?
01:11:42I want to comment is that is that there
01:11:45is sometimes sequencing done as part of
01:11:48newborn screening as a secondary test.
01:11:51So in other words,
01:11:53by using the various biochemical
01:11:55tests or even genetic tests that once.
01:11:58That some.
01:12:01Currently in fact some some
01:12:03sequencing is being done.
01:12:04I will acknowledge I'm I think.
01:12:07I think we have.
01:12:08This has to be done very thoughtfully
01:12:09and I'm going to give you a very
01:12:12specific example related cystic
01:12:14fibrosis newborn screening,
01:12:15which is done in many places by a
01:12:18combination of biochemical as well
01:12:20as by either reflex sequencing
01:12:21or in the state of California.
01:12:24Signal sequencing is done on every.
01:12:26Patient who is a positive IRTA test.
01:12:30And what happens in California?
01:12:32Because they do so much sequencing
01:12:34is that they identify many more
01:12:36individuals who have variants
01:12:38of unknown significance.
01:12:40And in cystic fibrosis they have a
01:12:43term that they use when you have one.
01:12:46Of the genes for cystic fibrosis.
01:12:48One of the variants that can cause
01:12:50cystic fibrosis and a variant
01:12:52that is not yet known to cause
01:12:54cystic fibrosis is unclear.
01:12:56It's unknown.
01:12:57And you have a normal sweat test.
01:12:59They then go ahead and say that you have
01:13:02a cystic fibrosis metabolic syndrome,
01:13:04which means that you don't
01:13:06have cystic fibrosis.
01:13:07You normal sweat test,
01:13:09but.
01:13:09We don't know whether other
01:13:11variant means and you might get
01:13:14cystic fibrosis and we need to
01:13:16keep testing you an one of my
01:13:18former fellows who I don't think
01:13:20she'll mind me sharing this who,
01:13:22like many of us in the world,
01:13:24worries a lot ahead of child who
01:13:27had this happen to Ann for her.
01:13:29This was a big worry.
01:13:32That that the fact that she.
01:13:35Was now said your child doesn't
01:13:36have cystic fibrosis,
01:13:37but maybe he could get it at
01:13:39some point for her was weighed
01:13:41very heavily on her and for her I
01:13:44think was very distressful to me.
01:13:46With this means,
01:13:47I actually think that newborn
01:13:49screening is an area where we
01:13:51have to be very careful for that,
01:13:53not only for that reason,
01:13:54but for a variety of reasons.
01:13:56So I do not see newborn screening
01:13:59shifting to a sequencing based model.
01:14:02As the first place this goes,
01:14:04will it go there eventually possibly?
01:14:06I think it will require a very
01:14:08careful thought about the curation
01:14:10of the information making decisions,
01:14:12which variants to report,
01:14:14which diseases to consider, how to do this.
01:14:17So I actually think.
01:14:19In 20 years we will be doing that,
01:14:22but I hope that the process to
01:14:24get there will have allowed us to
01:14:26develop how to do this in a thoughtful way.
01:14:29I also think that it raises,
01:14:31as has been discussed,
01:14:32for newborn screening in general raises
01:14:35new questions about informed consent
01:14:37in the following way is that.
01:14:39Historically, newborn screening is often
01:14:41done without much discussion with parents,
01:14:43and there's been a long gradual
01:14:45thrust in trying to do more
01:14:47education about newborn screening
01:14:48prior to delivery and at delivery,
01:14:51and I suspect if sequencing becomes
01:14:53part of it will be one more reason
01:14:56why there will be more education and
01:14:59more engagement at that time. So.
01:15:03Thank you the next question please,
01:15:05how do you counsel parents when you
01:15:08identify mutations with variable penetrance,
01:15:10even if predicted to be pathogenic?
01:15:14You know, I actually that's I think
01:15:18that's easier. I want to easier,
01:15:21it's more common. Because.
01:15:26There's many circumstances where the outcome.
01:15:31It's not clear what that's going to be,
01:15:34so let's take cystic fibrosis and diabetes
01:15:36and thinking about typically about two
01:15:38or three year olds for four year olds
01:15:40who are diagnosed with these conditions.
01:15:45What is variable? I mean,
01:15:47use patterns as an example as a metaphor.
01:15:50Which variable is the outcome?
01:15:52There are some children who
01:15:54have who will do really well.
01:15:56Other children who will do who
01:15:58have challenges, and so it's so.
01:16:01This notion of uncertainty that
01:16:02a copy is a clinical diagnosis,
01:16:05I think, is part and parcel
01:16:07with much of clinical practice.
01:16:09I think for some individuals
01:16:11that uncertainty is debilitating,
01:16:12but for many people they really.
01:16:15Adapt to that,
01:16:15and so I think there's many circumstances.
01:16:17I guess my own, as pulmonologist,
01:16:19I take care of children with chronic
01:16:21lung disease of prematurity.
01:16:22Putting kids were born at 2425 weeks.
01:16:24Have lung disease,
01:16:25that time that they're leaving
01:16:26the NICU there, oxygen,
01:16:28the feeding tube and you know what
01:16:30I can tell them is that I don't know
01:16:32where you'll be in three years.
01:16:34There's a there's a reasonable
01:16:35chance that you will be off all
01:16:37these supports and developmentally
01:16:38you're doing fine or you'll be
01:16:40off the support that you have
01:16:42developmental issues or vice versa.
01:16:43And I say you know.
01:16:45The the We don't know,
01:16:46but part of my answer back to your question.
01:16:49Patrick is one thing I say to my
01:16:52families myself is why I don't
01:16:54know where this will go.
01:16:55I'll be with you for that journey
01:16:57and we will continue to work together
01:16:59to sort that out over time and I
01:17:02think for me that's a critical issue
01:17:04as relates to genetic information.
01:17:05Is the notion of follow up
01:17:07follow up with their primary care
01:17:09provider or somebody else?
01:17:10The fact that the family feels
01:17:12like they're connected to somebody
01:17:14whom they can ask questions of.
01:17:16As time goes on.
01:17:19Thanks Ben I we've got time for one
01:17:21more question which I'm going to.
01:17:22I'm going to take myself if I can.
01:17:24You know you were talking about trying to
01:17:26get a sense from patients, for example,
01:17:28or subjects in a study for what you know,
01:17:31what if what whether they would or would
01:17:33not value this certain information and
01:17:34trying to trying to figure out that.
01:17:36Is this something people want.
01:17:38I'd be curious to know if there are data
01:17:40or if you've got personal experience with
01:17:42this about people looking in retrospect,
01:17:44not, you know,
01:17:44trying to figure out what they would want,
01:17:46but people who found out.
01:17:48Good news or bad news or
01:17:50equivocal news to people?
01:17:51Look after the fact in in
01:17:53parents or in patients directly.
01:17:55You know, I wish I hadn't known.
01:17:57I'm glad I knew someone studied that.
01:18:00Yeah,
01:18:00actually, we certainly
01:18:01have done a lot of that.
01:18:03We, you know, one of the things
01:18:05that we do as part of our vote,
01:18:08both the next Gen study,
01:18:09which was a carrier study as well
01:18:12as the charm is we do a range of
01:18:15of the side surveys interviews
01:18:16where we talked to people.
01:18:19That a month or so after the
01:18:21results disclosure to find out
01:18:22how that experience went with
01:18:24a follow the information and we
01:18:26also have done that where we take
01:18:28people who got negative results.
01:18:29Positive results were uncertain results.
01:18:31We also have a separate set of interviews
01:18:33that we did regarding this idea of utility.
01:18:36You know what's important to them as well,
01:18:38and so it's a way of trying to understand
01:18:41better what people think of this as well.
01:18:44Well, say is that.
01:18:45And this may be again even in this
01:18:48context of this selection bias,
01:18:50because people had to sign up for this
01:18:52and that most people don't regret it.
01:18:54They don't feel like God.
01:18:56I wish I didn't know this.
01:18:58They figure out how to sort
01:19:00of incorporate it.
01:19:01And so you know,
01:19:02while I still am sceptical and wanted
01:19:04and really want to urge caution.
01:19:06With how we roll this out carefully,
01:19:09we do it well.
01:19:11I'm less worried that most people have.
01:19:14Adverse consequences of the
01:19:16information itself,
01:19:16but I believe that the way we
01:19:18minimize that is by being thoughtful,
01:19:20but making sure resources are available
01:19:22and also by tempering our enthusiasm.
01:19:24And I think the example of back to
01:19:27the issue of newborn screening is
01:19:29really a good example where that's
01:19:31probably one of the last places I
01:19:33would want to go for doing this,
01:19:35but in the context of of somebody who
01:19:38is at risk for hereditary cancer syndrome,
01:19:40in the context of a family of a
01:19:42child who has parent development
01:19:44disabilities looking for the cause.
01:19:46I think it's rare that somebody
01:19:48has testing done,
01:19:50even if the result is an unexpected
01:19:52actual finding somewhere else.
01:19:53They're usually open to that
01:19:55idea that usually accept that.
01:19:59Thank you very much.
01:20:01Doctor Ben will fund this advance
01:20:03tremendous session tonight.
01:20:03We really appreciate it.
01:20:04We're sorry we couldn't do this in person,
01:20:07but sometime down the road we will
01:20:09absolutely get you to come join us.
01:20:12And thank you very much and I thank
01:20:13you all for attending on the website.
01:20:15You can see when the upcoming
01:20:17seminars are a bending.
01:20:17Like if you come here we take you out
01:20:19to dinner and but then you'd have a
01:20:21long flight home and all this stuff.
01:20:23So now you know no dinner but you
01:20:25get to just to kind of turn off
01:20:27the computer and put your feet up.
01:20:28No airplane right either.
01:20:31This is true. It's a pleasure to
01:20:32see all of you as especially you
01:20:35Mark and Karen and see you next
01:20:37time. See you next time.
01:20:38Thanks folks. Goodnight