[Dr. Andrew Singleton] So, I actually wondered, what do you think is the
biggest real barrier to releasing data from an
institutional review board perspective, especially in
studies across sites?
[Dr. Dan Levy] Well, I think from an IRB perspective, it would be
concern about identification of individuals.
And when you're dealing with a study that collected samples
from locations all around the world, that may not be such a
big concern, but when you're dealing with a study that's
located in a particular community, such as Framingham,
you know, a 14-year-old computer geek could pretty reasonably
identify a fair number of study participants from the data that
we have in our files.
You can go to the town hall in Framingham, and for $50 purchase
a copy of the town census that gives you people's names,
their telephone numbers, and their address.
You could get their date of birth, and you could try to
align date of birth of people who share the same last name
with the pedigree files that we have in the Framingham database.
So the big concern on the part of an IRB is whether we are
sufficiently protecting participants.
A number of times we've heard about the VA laptop computer
that was stolen with a lot of peoples' data.
In fact, I got a letter from the VA saying that my name was
among the names of individuals -- physicians,
whose data was stolen as part of that event.
So I think that would be the greatest concern.
Do you have an answer to that, or --
[Dr. Andrew Singleton] No, no.
[Dr. Dan Levy] So, my turn to ask you one, very quickly, and that is,
in our attempt to identify collaborators around the world
for replication of our genome-wide results,
we found some studies that seem to be very ready and
prepared to collaborate.
But, because other studies are aware that Framingham data will
go online on October 1st, some of them seem to have a
disincentive to want to share with us because it may mean that
now they have to share authorships and things
of that sort with our investigative team.
You know, there's one study I won't name, that happens to be
in Iceland, and another study that I won't name that happens
to be in -- I believe it's Augsburg, Germany --
that seem to be quite restrictive about the idea
of sharing and collaborating.
[Dr. Andrew Singleton] Yeah, you know, I think there are always going to be groups
who will take advantage of you releasing your data and making
your data available.
And I actually don't think that if someone is of that mindset
there is anything you can do about it, and perhaps you don't
particularly want to collaborate with that kind of person.
But for every person who does that, I think, or for every
group that does that, I think there are many groups who want
to truly collaborate and get your intellectual input on
pooling of data and analyses across studies.
[Dr. Dan Levy] Great, I see we have questions coming.
Hi.
[Femle Speaker] So one of the things that's -- I see changing, from the
perspective of the consents, for the genetics studies,
large-scale studies in particular, as data were
collected in many of the consent forms it's specifically stated,
"We will not be returning any information to you as a
consequence of any genetic studies done on the samples
that you provide us with."
But now there is an emerging ethical concern that as --
you know, if high penetrants, polymorphisms, are
characterized, that there is an obligation to return information
to study participants.
I was curious whether that came up in any of the discussions
with the Framingham participants.
[Dr. Dan Levy] Yeah, actually that's a terrific question.
And you may also be aware of the NHLBI working group that met to
address that question.
I think Teri was one of the people who organized that.
The paper is actually first authored by Ebony Bookman,
and it would be a useful thing for everyone to be aware of.
And it established three conditions for participant
notification, that there is an association that's identified,
that's quite strong for disease that carries substantial
morbidity and mortality, that we're dealing with a high
penetrance situation, so there's a high probability
someone will develop that disease, and most importantly,
that the knowledge of one's genotype would prompt a
treatment that will reduce morbidity and mortality,
prevent the development of disease, or prevent the
complications associated with that disease.
And certainly there were a few diseases that were identified
in that paper that will fall into that category.
I'd say one would be the hemochromatosis allele,
disease-associated allele, where identification of carrier status
might result in early treatment to prevent the development of a
significant disease.
And we approached our ethics advisory board.
In fact, our early consent form said, "We will not attempt to
identify you, even if we do find an important result."
And we've now redone our entire consent form, and what I didn't
share with you during my presentation was box number
eight and box number nine on our consent were permission to
notify you and, with your permission, your doctor about
genetic conditions you may carry that fall into those categories
of notification.
So we agree completely that there are conditions where
participants ethically should be notified, in particular when
there is an available treatment to prevent a disease or
its complications.
[Male Speaker] Yeah, as someone who's spent many years on a tenure decision
committee, I detect a little na vet about the importance,
or lack of importance, of being first or last author on a
major paper.
So this is not to say that people don't want to share data,
but it's a question of when; when it's shared.
And, so one of the problems with the GAIN project, for example,
was, I think, seen by many as a very short time between --
well, having short time to actually write your paper and
get it accepted for publication, which I think was initially six
months, and then it might have been extended a little bit,
knowing that there are people with very big resources,
who are part of the GAIN project out there ready to perhaps work
your data a lot more quickly and efficiently than perhaps you
could in your small university lab.
So the problem is, I think, in the timing of data release;
it's not the fact that it should never, obviously, be released.
But it's just the urgency that some people have been putting on
it being released.
[Dr. Dan Levy] So if I could summarize, it was a question accusing
one of the two of us of na vet .
Andy, I think that question was directed at you?
[laughter]
[Dr. Andrew Singleton] Okay. So --
[laughter]
-- thanks.
So, I guess I'll address the second question, and then we'll
get back to the na vet .
I think that one of the review criteria for the GAIN initiative
was that there was a solid analytical plan in place.
And while I take your point that there are powerful groups out
there to analyze the data, I think if the group that's --
if the group that's been reviewed successfully and
deposited the samples for the association can't do the core
analysis in nine months, then maybe they should,
you know, let other groups that can do the work get in there
and get the real result out.
The idea of this work is to find genes associated with disease,
and we should really strive to do that.
[Dr. Teri Manolio] [Inaudible] on the GAIN initiative, because I was
involved in some of the planning of that, and there was a lot of
debate as to what an appropriate time frame was, and what the
best data release policy would be.
And really where we came down -- I'd turn around to face you
Mike, but I'm afraid -- I guess this will come with me.
Where we came down was that we recognized GAIN was sort of a
new effort, a pioneering effort, and we really wanted to kind of
push the envelope a little bit, and we have, because now we
have the Genes and Environment Initiative and other programs
that are putting data out more rapidly.
But we recognize that it wouldn't be a good fit for
everyone, and it hasn't been.
But I think you're right, we need to examine multiple models.
And actually the way that GAIN works is the data are made
available immediately, as soon as they're
completed and cleaned.
But there is a nine-month moratorium on submission
of publication, so not actual publication, but
just submission.
In the CGEMS data there is no moratorium.
Once the data are put out there, anyone can use them, basically.
[Dr. Andrew Singleton] Just getting back to the idea of recognizing the need to --
for people for tenure -- to go up for tenure.
I mean, I think it's incumbent on those of us in the field
who do serve on tenure committees to make sure
that the committees understand that science, particularly
genetics and epidemiology, is moving towards these large-scale
efforts, and that we should perhaps shift away from focus
of first author publications and last author publications.
I realize -- I absolutely realize that it's going to
take some time for that transition, but the only
way it's going to happen is if we push that transition.
[Male Speaker] Well it is a long way from it, and in the meantime, obviously
there are people who are going through the process.
So it's a very difficult to --
[Dr. Dan Levy] Yeah, I agree, yeah.
[Larry Kushi] Hi, good afternoon.
Larry Kushi from Kaiser Permanente
in Northern California.
And I wanted to comment about data sharing.
Much of the emphasis has been on sharing the results of the
genome-wide scans, the 500,000 plus SNPs, or whatever, and
there was some discussion of sharing the phenotypic data,
which typically, at least has been described here, is that
that has been collected specifically in the context
of conducting, say an epi cohort study, or whatever.
So, the questionnaires, et cetera.
But in a setting such as I'm in, there's a third stream of
phenotypic data, which is the data that comes from clinical
and administrative databases that were collected specifically
for the care and sort of the tracking of the participants
in the health plan, and were not collected specifically in
a research study context.
And so, those data weren't really collected specifically
in a consented form, and yet they are available to us
as internal researchers.
And so, those data, probably more so than the data that
are collected specifically under research purposes,
are constrained by both proprietary interests,
as well as HIPAA and privacy concerns, and sharing of,
sort of, the medical data.
And even if they are anonymized, as has been pointed out for
some of the genotypic data, there is the potential for
being able to link it up and actually identify individuals.
And so, in that situation, given some of the other
challenges, like funding of investigators and sort of
professional promotions and all that other kind of stuff,
I really wonder how these data sharing agreements --
say, if we were to get NIH funding, which we do have,
and we extract data from these data sources that were not
collected specifically for research purposes but which
can be used in a research context -- how does that
impact what we are able to share?
I think that's a big question that we're struggling with
internally in terms of how these policies that are coming forth
are going to impact our ability to get funding, et cetera.
[Dr. Dan Levy] I know time is tight.
I'll make a few comments, and Andy may have a couple
as well.
I think it comes down to the actual language in the consent
that participants -- that your human subjects, even though
they came in for clinical reasons to Kaiser Permanente --
what they actually signed.
So I would recommend that you go back to your IRB with a copy of
the consent form.
As we did, you may want to form an ethics advisory board
that includes some of the members -- you're nodding
that you actually have done that.
And as a third step, you might want
to send your documents to a completely outside,
uninvolved group of individuals to weigh in,
as well, on their opinion about your ability
to perform certain types of research, or share data
from certain types of research with outside groups.
[Dr. Andrew Singleton] Yeah, I agree.
I think getting external advice is key.
I mean, I don't think that funding bodies will mandate
sharing every single piece of data you have.
They only want you to share what's relevant and what can
appropriately be shared.
I don't think that there's going to be a force to share
inappropriate data.
[Dr. Dan Levy] Debbie, if this is very quick?
[Dr. Deborah Nickerson] I just -- really quick.
In the genomics community, on sharing, people who share,
the more you share, the more information you get back,
the more information that you perceive.
And people who don't share don't actually get invited anywhere.