[MUSIC PLAYING]
We're going to move to a slightly different topic.
And I'm going to introduce on stage Imran Haque,
and he's the director of research at Counsyl.
He actually got his PhD in computer science
here at Stanford.
So somebody else with a connection to Stanford.
And then he moved on to become director of research
at Counsyl.
And really what he's interested in is big data.
And he's interested in novel advanced technologies
for genomic sequences and also how to analyze and share
large data sets and how to maybe interact
between these large data sets and clinical trial
and clinical testing.
So how do you go from this huge amount of data
you have to really helping patients in the clinic?
So welcome on stage, Imran.
Good luck.
Thank you, Julian.
And good morning, Stanford, and good morning, internet.
What I'm going to talk to you about today is what we can do,
what we do do, and the disconnect between the two
in perinatal precision medicine.
As Julian mentioned, I'm Imran Haque.
I'm the director of research at Counsyl.
We're a medical genetics lab in South San Francisco.
And in 2009, we were the first to introduce expanded carrier
screening with the Counsyl Family Prep Screen.
Since then, we've kept our edge by upgrading
generations of technology in our lab twice a year.
And we're now sequencing hundreds of thousands
of patient samples every year in our lab.
And by the way, we're open to collaborations.
Since we've started offering the Counsyl test,
we've tested over 365,000 patients
by expanded carrier screening.
And what I want to talk to you about today
is the insights that we've gotten
into rare genetic disease by doing this kind of testing.
In order to set the stage, let's first
examine the relative risks of different conditions
that can occur during pregnancy.
The 1980s really established the modern medical regime
for screening for prenatal conditions,
with the first effective tests becoming
available for Down syndrome, also known as trisomy 21.
In 1983, ACOG, the American Congress
of Obstetrics and Gynecology, established
the first universal screening guideline
recommending that women at high risk, basically
elevated maternal age of 35 or above, all
be tested for Down syndrome.
This is a condition that occurs at 35.7
for every 10,000 births in that population.
Also in the 1980s, the first serum screens
became available to test for neural tube disorders
like spina bifida, conditions that occur at about 1
in 1,000 births across the board.
Now, as time and technology marched on,
we were able to get more effective, cheaper,
and faster screening tests.
And by doing so, we were able to bring more rare conditions
into the fold, starting with universal screening
for trisomy 21 in all women, a condition
that occurs at 1 in every 1,200 pregnancies
even for women as young as 20.
And then moving on to inherited conditions,
like cystic fibrosis, and what Ricardo was just talking about,
spinal muscular atrophy, which occur in about 4 or 1
in every 10,000 births in the Northern European population.
Now, it's important to note that the particular diseases
for which we test are, in many ways,
a historical and technological accident.
They're the ones that were available at the time.
But an expecting couple isn't so concerned
about the details of trisomy 21 versus cystic fibrosis.
They want to know, will my baby be healthy?
So to that end, you might consider testing
for a much larger panel of inherited conditions.
However, when you look at these plots,
you might also be reasonable to think
that even if you add more conditions,
they're certainly only going to be as important as CF or SMA.
Maybe 4 people in 10,000 are going to have it.
If you look at the data, you'd actually be wrong.
It turns out that if you look at the 88 diseases on Counsyl's
panel, other than CF and SMA, that are at least as
bad as those two diseases, they affect 27
in every 10,000 births in the Northern European population.
That's a rate that's almost as high
as high-risk Down syndrome, something
for which we've had universal screening for over 30 years.
Now, what we have to consider is whether or not
this is actually going to generalize
to a large number of populations.
And in fact, a few months ago, ACOG and ACMG,
the American College of Medical Genetics and Genomics,
the other main guideline-providing agency
in this area, along with a number of other groups,
published a document which they titled,
"Points to Consider About Expanded Carrier Screening."
And in this, they raised two main questions.
They acknowledge that while this testing can have value,
they wanted to know whether or not this generalized,
or how important is the long tail of genetic disease?
And second, how are we actually going
to deliver all of these results?
I'd like to use our experience testing
over a third of a million patients
to shed some light on these questions.
First, does this result generalize beyond Northern
Europe, or is this something that's
really localized to one genetic population?
The answer, of course, is that yes, it's a general problem.
What I'm showing in this slide is the fraction
of births affected by a severe or profound genetic condition
on Counsyl's panel that would have been detected by existing
carrier screening guidelines promulgated by either ACOG
or ACMG.
What you see is that only African Americans come out
looking relatively well-covered here.
And that's primarily because of sickle cell anemia,
which has a shockingly high carrier frequency.
About 1 in 10 African Americans is a carrier for this allele.
Now, Ashkenazi Jews are an interesting case study.
Their detection rate is 41%, which
is higher than everyone else, primarily
because a number of Ashkenazi-specific conditions
have been added to their ethnicity-specific panel.
However, when you look at every other group,
you see that the detection rate is shockingly
low, from one in four in Southern Europe, to 1 in 20
in the Middle East.
What this means is that current screening guidelines are really
missing between 75% and 95% of births
that we could detect today with current technology.
And these are diseases that really matter.
Jen and Joe Baumgartel were a couple
who had no previous family history of genetic disease.
But when they took the Counsyl test,
they learned that they were both carriers
for Smith-Lemli-Opitz syndrome, a profound disorder that
can cause miscarriage and that, if the child is born,
can cause physical or intellectual disability.
They were able to take this information
and do something positive with it.
Using IVF PGD, they were able to conceive a healthy baby
daughter Kinley.
So this is half the story.
We know that there's quite a lot of so-called rare genetic
disease out there.
We know how to detect it.
And we know that it's actually important.
The second part of the question is, how do we actually
counsel and deliver these results
to patients and providers?
The traditional solution is to deliver the results
in the context of a doctor's appointment
or a genetic consultation session.
The problem with that is the scaling
that was talked about in the plenary this morning.
Basically, the pace of genetic testing
is scaling exponentially as the cost of sequencing has fallen.
The problem is that the number of certified genetic counselors
in the United States has only grown by about 5%
per year for the last five years.
This disconnect means that in a large number of institutions,
patients have to wait multiple weeks in order
to get the results delivered to them by a genetic counselor.
In an era where you can get the sequencing done
in just a couple of days, it really
doesn't make any sense to make patients then
wait another two weeks to get the results delivered.
So what do you do?
Our solution was to completely re-engineer the process
of laboratory resulting.
The very first step was to move results to the web.
After creating an account on our website,
patients are able to track their sample in real time
as it makes its way through the lab.
And then when the result is done,
to log on on their phone or their computer
and see the results right there.
But that's not enough.
If you were just to deliver a traditional laboratory test
result over the computer, it wouldn't help anyone
because it would be incredibly confusing.
So we fully re-engineered and redesigned
the lab report itself.
If you were a carrier of CDG Type-Ia,
and you logged into the website to see the results,
you would see something like this.
Right up top is a summary of the one result
that you actually care about.
Instead of seeing a long laundry list of conditions,
you see the important stuff right up top.
And then when you scroll right below,
you actually see a series of videos recorded
by our genetic counselors that are tailored
to exactly your results scenario that explain what you have
and explain next steps.
Now, by putting resulting before a counseling session,
we're enabling what we call genetic counseling
triage, basically the notion that a lot of patients,
if their information is delivered
to them in a well-designed and well-thought-out way,
might not need a full counseling session.
That said, everyone who gets a Counsyl
test is entitled to get a full genetic consultation session.
And in fact, in 2014, we did 11,000 genetic consultations,
enough to put us in the company of institutions
like UPMC and the Mayo Clinic.
Now, while at other institutions patients
might have to wait a couple of weeks to speak to a counselor,
half of our patients were able to get a consultation
through Counsyl within just a few days.
That doesn't sound very good, until you consider
that the other half were able to get their consultations
within minutes.
Last year, 46% of our consults were
done using what we call on-demand genetic counseling.
Patients who were getting their results delivered online
could click a button and, within just a few minutes,
be speaking on the phone to one of our genetic counselors.
Let's look at the data to see what this translates to
in practice.
What I'm showing here is the fraction
of couples who had different result types who
needed counseling on the bottom and then, on the y-axis,
looking at how long those consultation sessions took.
Now, there's a bit of systematic bias in the numbers
at the bottom because some clinics choose
to counsel results themselves rather than
letting our GCs handle it.
But the trend is clear.
When the result is well-designed and well-delivered,
there are a large number of couples, particularly
those receiving negative or no-disease-detected results,
who don't need to speak to a genetic counselor.
They've gotten the information they need through self-service.
The other interesting thing is when you look at the graph
itself.
Look near the top, at the dashed line at 30.
That shows a half hour, the quantum of time
in which typical genetic consultations are reserved.
The reason for that is because in a typical hospital setting,
genetic counselors have an awful lot of paperwork
that they have to fill out associated with a consult.
We use technology to shift this busy work onto computers
and away from our genetic counselors,
meaning that once they spend the time with the patients,
they don't have to spend another 20 minutes on paperwork.
They can use that to speak to the next patient,
making the best use of a scarce resource, a counselor's time.
So let's recap.
What I wanted to show you today was the disconnect
between what we can do and what we do do.
I showed you that even though we have the capability
to test for hundreds of genetic conditions,
current guidelines are missing between 75% and 95%
of affected births in preconception and prenatal
testing.
And even though we have the technology
to have patients speaking to counselors within minutes
of getting their results, in many cases
we're currently making them wait weeks to speak to a counselor.
The upshot is that, in many cases,
it's not going to take magic or science fiction to deliver
precision medicine.
Simply by implementing technologies that we know now,
we can actually bring this into the clinic today.
Thank you.
[APPLAUSE]