Genetic Information Disclosure and Whole Genome Sequencing

Transcript

• 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