+ 00:03:23 - Experts answer "How will COVID impact cancer
clinical trial research?""
Lisa Laudico:
We all have been living with a heightened understanding of the vaccine trial process and other elements of
the pandemic response. We heard from guests in episode one of the series that medical research has, in many
ways, lagged behind other forms of research. And now with COVID, we see processes that would normally take
months or years being completed in a matter of days. We asked our expert panel why the same sense of
immediacy is not applied to cancer clinical trial research. Here's research scientist, Corrie Painter.
Corrie Painter:
I do think that there are tons of lessons to be learned about our experience with COVID. And I think that
chief among them are that you can move mountains if you absolutely disrupt the system. Basically we were hit
with COVID and the whole world was like, what's everything we can do to fix this? And when you do that and
people's lives are on the line and civilization is on the line, it wakes people up and it makes people say,
Oh, wait a minute. That whole paywall with respect to papers. Let's just pause on that so that everybody can
get the information they need as fast as possible, because we must need that in order to make the next step
forward. So if you look at what was disrupted in order to make these things happen overnight, that's a clue
as what we need to do for cancer research as well.
And so peel it back to the fundamentals. What did we do? Well, we got rid of every paywall there ever was
with information. Information was just freely shared from every single journal, and scientists put
everything they were discovering into pre-prints for the good and for the bad. It's not all good. There's a
lot of misinformation that got shoved into these pre-prints, but at the same time, a lot of really useful
information. And it just meant that people had to be judicious with what they were pulling out in terms of
information. But underlying thing for me was the flood of information.
Jim Kremens:
We should pause here and remind ourselves what a pre-print actually is. Think of them as info published
before it would normally be printed in a peer review journal. So any pre-print is not formerly peer
reviewed, but as Kristin Schneemann pointed out in our last episode, this information can be evaluated
quickly by the community for misinformation or bad science.
We saw that during the rapid treatment evaluations that were released in pre-print so that all researchers
working on those questions globally could share more quickly than if we all waited for peer reviews and
publication schedules. This leveraged the notion that not all research is perfect. Not all ideas are good
ones, but if we increase the speed with which information can be shared in the worldwide scientific
community, we're getting peer review in real time.
Sarah Mann:
Agreed. And it just seems like a much more transparent and iterative process overall, which would improve
the advancements.
Lisa Laudico:
We asked Corrie what she thinks will stick in terms of positive change that was demonstrated to work
effectively in this COVID era and how it can be translated to cancer research.
Corrie Painter:
I think that, tele-health is probably here to stay because there are new laws. There are new laws that make
doctors able to actually practice medicine across state lines that did not exist before COVID. I can't
imagine that those laws will be reversed - that's going to benefit the cancer patient and that ultimately
will benefit cancer research as well. I think that there was a lot negatives too. And so philanthropy from
the nonprofit sector in cancer research took a massive hit, right? There was no galas, there weren't any
races. So these nonprofits that are really critical across the board, funding individual investigators and
all the way to funding postdocs - a lot of those have dried up.
Lisa Laudico:
And here's bioethicist Jill Manning on the question of COVID advancements and the decentralization of
clinical trials.
Jill Manning:
I do think that when it comes to looking at how fast we were able to get that vaccine, we were building on
25 years of research that was already in effect for the SARS virus. So there was a lot of groundwork that
scientists had already done and were able to hit the ground running, so to speak. We're also talking about
vaccines, which is very different than investigational drug to cure cancer.
You also bring up an extremely important point about the centralization of these trials. In the last 10
years, IRBs have seen an enormous increase in single IRB review and central IRBs that are overseeing these
trials, and of coordination - allowing for faster recruitment to happen, less redundant work, removing a lot
of administrative barriers that slow down the process for everyone, allowing for quicker approvals of
amendments and changes to protocols - and amendments are also a key consideration here when we're talking
about research and the abandonment of non-effective trials.
And that also goes back to adaptive trial design. I guess I should say, in most cases where you have
adaptive trial design, by nature of it, you need an enormous cohort and multiple sites. And those are almost
all going to be a central IRB or a single IRB. And we now have a federal single IRB mandate because we've
seen how much faster and how much more effective the running of these trials can be when we have that. So
that was in place pre COVID, and I think that we can absolutely expect to see a continuation of that moving
forward.
Lisa Laudico:
We asked oncologist Dr. Fischbach if he thought the innovative science behind the COVID vaccines may help
expedite the search for a cure for metastatic breast cancer.
Dr. Neil Fischbach:
Advances come in funny, different places, and it's hard to predict. This is why our government needs to fund
basic science research even at its most basic understanding how proteins fold, understanding how cholesterol
metabolism works. These may be where the next big discoveries come from. I think one critical thing with
COVID, is just the pace with which something got from a lab into people. And the idea of, we need to
continue to be accelerating how fast we can move these discoveries, I think will have a real impact on
cancer medicine. I think that that together with the sense that we are more and more thinking of cancer,
less as that it started the breast lung or colon and more about what are the genomic- it's the sum of the
parts, what are the molecular underpinnings of the cancer. And so being able to disect the COVID virus
within a month and identify how a virus works. Well, why can't we do the same for a cancer cell? Why can't
we identify each individual's cancer cell? What are the unique features and develop therapies accordingly.
Lisa Laudico:
I think there's the fear that once COVID is behind us, before the next pandemic comes down the pike, it'll
slow down everything again, people will go back to their bunkers, go back to their silos and the
communication and that collaboration, which became so critical to the success of the COVID vaccine effort,
that that would also be the situation for cancer. That we'll just go back to the way things were done
before, inertia will return.
Dr. Neil Fischbach:
I don't share that concern. Being privy to how things are being organized at Yale and the pace with which
collaborative arrangements are being made between really disparate disciplines. This is really the emphasis
of every big academic center - putting pieces together that you wouldn't ordinarily think of: chemists,
mathematicians, other basic science and clinicians all sitting in the same zoom. And the zoom thing. That's
had a real impact, who ever would have thought of having a zoom meeting before, and now it's routine. And so
building these collaborative networks is getting easier, not harder. I'm actually more optimistic that with
this new way of life with zoom, that it's going to accelerate the pace of discovery rather than everyone go
back to their isolated labs when we're all done with this.
Lisa Laudico:
What advances have you seen in clinical trials that are conducted for the COVID vaccines that seem to be
advances that we might want to take some lessons from?
Here's Kristin Schneemann, the director of FasterCures, with her thoughts.
Kristin Schneeman:
Yeah, absolutely. And again, just by way of context, we have faster cures have spent a fair amount of time
over the last six months or so really trying to capture a lot of the lessons that we are learning in the
course of the pandemic about how we can make biomedical R and D better and faster. I think we pretty quickly
realized last year that a lot of what was occurring was laying bare a lot of problems that have been true
for many years across all conditions, but they were just really coming to the fore in COVID.
But we were also seeing people just innovating in really incredible ways because of the emergent situation
and collaborating with one another in ways that they're not accustomed to, across companies, across sectors,
accelerating the process of therapeutic and vaccine development in ways that we have never seen before that
no one had ever really contemplated was possible. And clinical trials being conducted in just incredibly
rapid fashion. So we really wanted to capture that energy and those ideas and hopefully, create some energy
around trying to pull them into the future.
And so some of the things that we saw really come to the fore during COVID were an explosion, honestly, of
things like master protocol trials, which is basically that you have a single trial where you can test
multiple products. Sounds pretty straightforward. It's actually, you know, fairly complex from a trial
design standpoint and a statistical design standpoint. But this is an innovation that has been developing
over a number of years. The FDA has been very supportive of and promoted with sponsors and the ones that we
have really seen in previous years, were in oncology.
So lung map is a lung cancer master protocol, I-SPY is a couple of those master protocols in breast cancer.
And there's one in pancreatic cancer. So that is a model that was really starting to flourish in the cancer
community. And just beginning to start to kind of leak out to other conditions as well. And all of a sudden
in COVID, there were 14 of them, out of nowhere. We've been promoting this idea for a number of years and it
was like, Whoa, where did, how did that happen?
And FDA has actually been, and Janet Woodcock in particular, the acting commissioner now, have been diving
into a lot of the data around the trials, both for COVID vaccines, but also therapeutics that have been
going on, there are hundreds and hundreds of them, and came out with some sort of depressing statistics that
94% of those trials are not likely to generate any actionable evidence because of the way that they've been
designed. Many, it turns out are just too small. Many of them don't have controls. There are all sorts of
reasons why, in the FDA's view, they're not going to generate any actionable evidence. So they're a bit of a
waste of time and patience and money which is unfortunate. But of that, the 6% of all of those COVID trials
that the FDA looked at, the majority of the ones that they did think were going to generate action and some
of them have been generating actionable evidence are these master protocol trials.
Jim Kremens:
So the lesson here is that master protocols should and are being promoted during COVID, and it looks like
they should be continued.
Lisa Laudico:
I love that more and more partners were involved, and there was just more transparency.
Jim Kremens:
That seems good.
Kristin Schneeman:
Another innovation that really has come to the fore during COVID is how we can better use real-world data
and evidence. Data and evidence about things that are happening in the real world with real patients and
real healthcare settings - how we can use that to better inform clinical trials and clinical research. And a
specific example of that is something called the COVID evidence accelerator, which is a project that was
created by the Reagan Udall foundation for the FDA. It's separate from the FDA. It's a nonprofit that raises
money for FDA and does projects on behalf of FDA. And they worked with a group called friends of cancer
research on this effort. Initially, it was a project that was cancer focused, and the idea was to create an
environment, a platform, for lots of people who have data to come together.
One person described it as a pickup game, like in basketball where all these players come together and share
information about what data they have. They don't actually share their data, in this case. But they share
information about what data they have, how they've gathered it, how they think they should analyze it. They
all talk together about what questions they have that they think this data could be applied to. And then in
some cases they actually do little exercises or experiments where they say, okay here's a question. You
three people who have data go off and answer this question with your data. And then we're all going to come
back together and compare results.
So this was something that they were developing in oncology that was a really interesting and, by all
accounts, incredibly valuable platform and opportunity. And it's not just the big academic medical centers -
it's local community healthcare institutions are a part of this group, big data companies, companies that
are usually thought more of as vendors then participants really, FDA is part of these conversations.
And they had this going in oncology and, of course, when COVID hit, everybody's Oh, I need to apply this to
COVID. And it has just been an incredibly valuable, again, opportunity or platform for all these people who
usually compete to come together and talk about how they can collaborate. And again, they're not sharing
their data, they're not putting it like in a common pool, so they're not dealing with, competitive
challenges, but they're figuring out a way to still work together, to answer questions and to solve problems
about how can we use this data more effectively to answer these big questions that we have.
Lisa Laudico:
It's fascinating what you're saying, because it sounds to me that COVID has taken the profit motive a little
bit off the table, and there's a little bit more democratization of analysis rather than data.
Jim Kremens:
For the cancer patient, of course it is frustrating. Why can't they collaborate? Sure, we get that R and D
takes a lot of money.
Sarah Mann:
Doesn't Tesla open source all its patents? They seem to be doing okay, right?
Lisa Laudico:
Holding onto the data, which is holding onto the recruitment of subjects for a trial or participants for
trial. Am I right to say that's the proprietary information that a drug sponsor, a research entity wants to
hold onto because that's their competitive advantage. Am I right?
Kristin Schneeman:
I think that is very often the case. Certainly not always, but very often, one of the challenges in this
whole ecosystem is the fact that many of the players who hold data view it as their competitive advantage,
their property, even if it's data about you. So they are reluctant to share it, but I think one of the
things that got magnified during COVID was that there are ways to work together that are pre competitive. I
think COVID helped show us maybe a little more clearly that you can stretch those boundaries. People are
still gonna make money here on caring for patients, on developing therapeutics.
And part of what we're advocating for faster cures is, before we all go back to our day jobs and forget
about this experience, let's really analyze some of these collaborations that came about during COVID in
detail and understand, how did we all work together? Where did we set those boundaries for data sharing?
What kinds of legal agreements? People were putting legal agreements in place in a week that previously they
would say, Oh, this would have taken us six months or a year before COVID. So we really want people to
analyze it at a level of detail, how did we do this so that we can keep doing it? So we don't have to go
back to taking six months to a year to put a legal agreement in place.
Another great innovation that came out of COVID was that NCATS, one of the roles they play is to sit on top
of this network of clinical and translational science institutions all across the country. So I don't know
how many there are now, 60, 70. These are the big academic medical centers all over the country that get NIH
funding to do clinical research.
Lisa Laudico:
So NCATS stands for National Center for Advancing Translational Sciences.
Kristin Schneeman:
NCATS is the wrangler of all of those institutions. And for years, they've been trying to get those
institutions to agree to share their data, actually share their data, connect all of their EHRs and other
data in a centralized platform. And they haven't been able to get them to do it.
Lisa Laudico:
Again, this is the lay person sitting down, listening to this information and saying the NIH is giving you
money, and the NIH is politely asking you to share your data. To the other people that we give money to, it
seems to me like it's a criteria we give you money. We ask you to share. Am I speaking like a crazy person?
Kristin Schneeman:
I certainly don't think so. But COVID was the forcing action that actually got them all to agree, to sign
the data, use agreement and have their data, what they call harmonized. So as we all know, the data amongst
our different doctors and healthcare institutions doesn't talk to each other very neatly and nicely. It's
not really interoperable. And that's true across these different academic medical centers often as well. So
there was a certain amount of technical stuff that had to happen with the data to, to harmonize it and make
it so that you could share it and compare it and do work across it, but it happened. And so all this work
they've been doing for years to try to get this platform in place has now been done, and it was done
specifically for COVID, but they can use that now for anything that they want to use it for.
Sarah Mann:
And here's Deb Collyar of PAIR with her assessment of the impact of COVID on the clinical trial process in
the U.S.
Deb Collyar:
COVID is bad for all of us, but there are a few good things that are coming out of it. And one of them is
better clinical trials for patients. Which is what we've been asking for for decades now. Things are
starting to happen. Tele-health visits, more local procedures that can be done, whether that's lab tests or
even treatment sometimes right. Home delivery kind of stuff. Not only for drugs, but for nursing care, and
of course technology allows more devices, more ways to collect more information. But what I keep explaining
to all of the data folk, of which I come from in my career, is that we have to follow with it.
So there's a marketing fundamental called WIIFM, which is what's in it for me. We turn that around and say,
what's in it for patients? If you continue to want to take more and more from patients, forget it. This has
to be a two-way street. While you get the complete data sets that you want and need to be able to move
forward in the future, what can you also give to that trial participant right now that will help them -
because technology can allow us to do both of those things at the same time. They're just not thinking about
it. And the good news is there are more of them thinking about it.
Other things that need to happen there would include adaptive design trials and platform trials. Those kind
of go hand in hand, but they don't have to be the same thing. Adaptive design can be complicated, but we
don't have to get into the weeds. What it really means to patients is that the trials learn along the way as
they go. It's built into the protocol. So it's not an ad hoc, oh, what if we do this kind of thing? It's
actually built into the trial design to look at the data at different points of time within that clinical
trial. So if we start to find that one arm of the trial or the study is doing better than the others, then
they can readjust randomization for example. So that, instead of it's a 50 50 shot that you have, or a
one-to-one, they can change it to a two to one or a three to one.
So you have a better shot at getting either something that might be working better or in a platform trial
where you have more than two arms, for example, you have a better shot at getting something new. And so
those things are advantageous to patients. They're actually advantageous to research too. It helps make the
research go faster.
It's really important that we also include more patient relevant end points into the studies, because - this
gets to the point that I've had conversations in the metastatic breast cancer world many times and I bring
out in presentations all the time - is that we don't want to be treated as surrogates for earlier disease.
We want the needs of metastatic patients to be taken care of in that trial. Because that's the only way
we're going to learn what's going to work best for the metastatic community as well. And so having patient
relevant end points for that patient population, whoever it is in that study, is really important.
Broader eligibility is critical because the trials really don't make a lot of sense in the real world. And
when I say real world, I don't mean what the data geeks think. Patients' real worlds and all of the pieces
that we have to put together. I'm encouraged because FDA is actually involved with other groups, like
friends of cancer research and some other groups like that, looking for expanding eligibility criteria.
Pre-planning is really important too, just as a pragmatic, kind of operational, thing that we could actually
have everybody start doing immediately. It takes a little more time upfront. But it really streamlines the
clinical trial process, shortens it, reduces the number of amendments which can cost millions and millions
of dollars. And then what I always tell companies when we go through that is that means also that the
patient community gets to benefit from your cost reductions too. So let's stop making drugs that are
unaffordable and causing financial toxicity, which actually has been proven to shorten survival. And if
we're all working together, we should all reap the benefits from that.
Lisa Laudico:
We couldn't agree more with Deb Collyar in this movement for clinical trial pre-planning on the part of the
sponsors and researchers so that patients can benefit from less financial toxicity and the process reflects
our reality better. Clearly COVID has helped researchers to move more nimbly with more transparency. And we
agree with our guests and hoping that these changes that were discussed will continue.
In this episode, we wanted to highlight our guests and their initiatives in the clinical trial space. We've
been speaking with Kristin Schneeman of FasterCures, Corrie Painter of Count Me In, Christine Hodgdon of
stormriders.org and grasp, Lianne Kraemer representing the MBCA's Marina Kaplan project and Deb Collyar of
PAIR All of their links will be in our episode notes along with a toolkit for people living with MBC looking
for clinical trials and other resources. To start off, here's Kristin Schneeman on advocacy groups in the
oncology research space.
Kristin Schneeman:
I think what we've seen over the 15 years or so of our existence is that there are more and more of these
groups that are trying to figure out how can we be more effective in our role. I think there's just come to
be a growing awareness that funding more basic science does not necessarily result in more products that
patients are able to take.
The other realization that many groups have come to is that if their mission is to get more products to
patients or better treatments or better care to patients, if your organization's mission is that, stopping
at the funding of basic science and that's it, is not achieving your mission.