Clinical Trials: The Patient Perspective Part 2

Join us for Part 2 of this two-part series on Clinical Trials from the Patient Perspective.   This time we hear from the experts who have solutions to the issues raised in Part 1.  We continue to explore how research processes were impacted by Covid 19 and the race to find vaccines and treatments.  Spoiler Alert – there are some Covid silver linings for those of us looking for change in MBC research.  Co-hosts Jim Kremens, Lisa Laudico, and Sarah Mann, speak with experts Susan Colen of BreastCancerTrials.org, Deb Collyar of PAIR, Dr. Neal Fischbach of Yale New Haven Health, bioethicist Jill Manning of Mass General Brigham, Dr. Corrie Painter of Count Me In and the Broad Institute, Kristin Schneeman of Faster Cures and the Milken Institute along with MBC Patient Advocates, Christine Hodgdon of GRASP & Stormriders.org and Lianne Kraemer.

Follow along with our transcript below.

Check out our guide to clinical trial resources and search tools here.

Want more about things Mentioned in this Episode?

Find Clinical Trials for MBC at Metastatic Trial Search and check out Metastatic Trial Talk for related information and resources. Both of these are part of BreastCancerTrials.org and follow them on Twitter @bctrials.
I-SPY Trials master protocols in breast cancer.
Read more on the FDA and the Reagan Udall Foundation announcement on the evidence accelerator.
The National Center for Advancing Translational Sciences (NCATS) — one of 27 Institutes and Centers at the National Institutes of Health (NIH) — was established to transform the translational process so that new treatments and cures for disease can be delivered to patients faster.
Faster Cures at Milken Institute. Follow Milken on Twitter
Learn more about the Metastatic Breast Cancer Project at Count Me In and find out how to register.
You can also find clinical trial information at Christine Hodgdon’s Stormriders website. Christine has a two-fold mission - 1) to provide the most up-to-date scientifically accurate information about breast cancer and its treatments, and 2) to distill this information into a digestible format that is easy to understand.
Join the Facebook Group MBC Trials and Innovation
What is the FDA’s Patient-Focused Drug Development? Find out here. And read more about Compassionate Use and Expanded Access from the FDA. The American Cancer Society has a good article on Compassionate Use.
Read new guidelines for clinical trial eligibility for brain metastasis. ASCO details several FDA changes here.
MBC Alliance #HereAllYear focuses on Clinical Trials 101 in March. Read and hear more patient stories. The MBCA is the home of The Breast Cancer Brain Metastasis Initiative (The Marina Kaplan Project)
MBC Connect - MBC Connect 2.0 is an interactive, web and mobile-friendly patient registry where you can share information about your MBC disease history, experiences, and quality of life – and now, get potential matches to clinical trials. Also available MBC Connect Español

Meet the Guests of this Episode

Lianne Kraemer

Lianne is on the MBC Alliance committee for The Breast Cancer Brain Metastasis Initiative (The Marina Kaplan Project).

Why the Women Most Likely to Die of Breast Cancer Have Gotten the Least Attention

Christine Hodgdon

Visit GRASP or follow on twitter. Christine is #HereAllYear talking about How Clinical Trials Can Treat Metastatic Breast Cancer.
Breast Cancer Survivor’s Journey from “What Did I Do Wrong” to “What Can I Do Now?”

Deb Collyar

Director, PAIR (Patient Advocates in Research)
What's Being Done to Make Clinical Trials More Accessible?

Susan Colen

Director, Metastatic Trial Search
Breastcancertrials.org

Dr. Neal Fischbach

Assistant Professor of Clinical Medicine at Yale School of Medicine. Follow YaleMed on Twitter

Kristin Schneeman

Director of Faster Cures at Milken Institute. Follow Milken on Twitter

TRAIN -the Research Acceleration and Innovation Network

Jill Manning

Bioethicist and Assistant Director of the Mass General Brigham Institutional Review Board

Dr. Corrie Painter

Associate Director of Operations and Scientific Outreach for the Broad Cancer Program

Here is a list of organizations and individuals to follow on Twitter. Thanks to Christine Hodgdon and Julia Maues, founders of GRASP, for compiling and sharing this with all of us.

Organizations/Initiatives

Doctors/Researchers

Advocates

Media (Podcasts, magazines)

Conferences

Trial-related

@abreastcancer

@AdvocateCollab

@Angeldisguise_

@ASCO

@ASCOPres

@Breastcancerorg

@CancerAdvocacy

@chrysalisinit

@ciitizen

@ConquerCancerFd

@curetwistedpink

@GRASPtweets

@LivingBeyondBC

@LobularBCA

@MBC_Project

@mbcalliance

@MBCNbuzz

@metavivor

@NCIDirector

@OncoAlert

@ProjectLifeMBC

@rethinktweet

@SHAREing

@sistersnetwork

@SU2Cscience

@the_rightdose

@thebreastofus

@tigerlilycares

@touchbbca

@ABhealer108

@aftimosp

@AileenIlianaPhD

@AlanaWelm

@amykpatel

@aszim13

@awolff

@ayshakhoury

@benhopark

@CareyAnders1

@cittelly

@DanielleKrolMD

@Dr_RShatsky

@DrAttai

@DrBOvermoyer

@DrDebuTripathy

@drdonsdizon

@DrEricWiner

@DrGattiMays

@DrHBurstein

@drjennifergao

@DrJuliaBeaver

@DrRBarroso

@drsarahsam

@DrSGraff

@DrSusanLove

@DrWinkfield

@E_de_Azambuja

@elmayermd

@EMittendorfMD

@EnriqueSoto8

@ErikaHamilton9

@FAndreMD

@FilipaLynce

@gary_lyman

@GeorgeSledge51

@GhajarLab

@hmcarthur

@hoperugo

@jamienholloway

@JennGuerriero

@JenniShengMD

@JenRicher3

@jesusanampa

@jrgralow

@KalinskyKevin

@kevinpunie

@lab_bcm

@maryam_lustberg

@MCristofanill

@MridulaGeorgeMD

@naborala

@ndenduluri1

@NeNe_LaShaun

@NicoleKuderer

@Nikhilwagle

@nlinmd

@oesterreichs

@Otto_DFCI

@PTarantinoMD

@Prof_Riggins

@RitaNandaMD

@SKabrajiMD

@stolaney1

@StoverLab

@TarahBallinger

@tmprowell

@VeredStearns

@weoncologists

@YoungStrongDFCI

@abcdiagnosis

@AMJohnston1315

@barbarasegarra

@bobriter

@BraveBeauty26

@Bronxborn409

@ChefGeib

@christeeny513

@coffeemommy

@cormerod

@corrie_painter

@debsetu

@double_whammied

@ESchattner

@HillStirSci

@IBCResearch

@itsnot_pink

@itsthebunk

@jamilkali

@JaniceTNBCmets

@JersiBaker

@JillHoldren

@KDRichardson924

@LesleyKailani

@lianne_kraemer

@LLaudico

@LPseattle

@Maimah

@malefitness

@marissadt28

@Martha__Carlson

@MichelleTregear

@MyBreastYrsAhd

@MyStyleMatters2

@NancysPoint

@paspears88

@pink4the

@raalbany

@RickiDOVE

@sandisues

@Sharon4ACure

@stage4kelly

@stales

@Stickit2Stage4

@swaggsheila1

@TerlisaFights

@tperrybrown

@3BlackDocs

@ourmbclife

@MarciALandsmann

@OncLive

@AACR

@MetastasisRS

@MetastaticOdds

@myESMO

@SABCSSanAntonio

@BCTrials

@eaonc

@NCICancerTrials

@SWOG

Transcript

+ 00:00:00 - Introduction

Lisa Laudico:

From SHARE Cancer Support, welcome to Our MBC Life, a podcast dedicated to exploring life living with MBC, with the advocates and experts who help make our lives better. This is Part Two of our two-part series on clinical trials. This episode, we'll hear again from experts, Dr. Neal Fischbach, Jill Manning, Corrie Painter, and Kristin Schneeman, and also MBC patient advocates, Lianne Kraemer, Christine Hodgdon along with the director of Metastatic Trial Search, Susan Colen and the director of the Patient Advocates In Research, or PAIR, Deb Collyar.

Jim Kremens:

In part one, we focused on identifying some of the issues or problems with clinical trials from the patient perspective in the U.S. Issues like clinical trial design that can keep patients from access to a clinical trial that would otherwise be right for them or rigidity in how the clinical trial is managed, creating onerous often unnecessary burdens on the patients.

In part 2, we're going to dig into some of the exciting solutions and changes that are coming to how clinical trials are designed, managed, and monitored. We asked our panel of experts what they felt has been learned from the work to find treatment and vaccine for COVID-19 and whether this can positively impact cancer research. Since we all know that the cure for breast cancer will come from the clinical trial process, we asked our panel why a cure for breast cancer has not been found yet.

Sarah Mann:

For patients, we have recommended finding a clinical trial through a clinical trials search engine, like those powered by breastcancertrials.org, which creates the metastatic trial search tool found on the MBC Alliance website, on the SHARE cancer support website under MBC resources, and on other nonprofit organizations serving the MBC community.

To learn more about these trials search engines we spoke first with Susan Colen of breastcancertrials.org.

+ 00:01:49 - Susan Colen & Metastatic Search Trial

Susan Colen:

I lost my mother to breast cancer when I was five. So this term came up at some point, previvor, which I thought, that's what I've lived with my whole life. I got this job at breastcancertrials.org in 2009. It was the perfect combination of my interests and skills. It was Ellie Cohen who founded BCT and was the only full-time staff. I was the second full-time staff and ended up working with her and growing BCT, breastcancertrials.org, to expand to Metastatic Trial Search. And we also have developed a technology platform that can match these eligibility criteria to patient data for all cancers and all diseases. It's another part of our work. It's very fulfilling.

The hypothesis behind metastatic trial search, which we developed in 2015, firstly, we were hearing that the metastatic community wanted something that was more specific. They didn't want to sift through trials that were clearly not relevant for them. But the idea was we actually adapted what we had for MBC specific trials in a collaboration with five other advocacy groups. And the hypothesis was, let's build an application that we could embed

Lisa Laudico:

into their websites. Cause that's where the people are.

Susan Colen:

We don't want to reinvent the wheel either. We'd love to collaborate and we're open to collaboration.

+ 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.

+ 00:26:11 - Faster Cures: Kristin Schneeman

Kristin Schneeman:

So I am a director at an organization called Faster Cures. We are a center of the Milken Institute and we are a think tank, essentially. We hope we're also a catalyst for action and not just thinking. But as our name implies, our interest is in "what are the issues in the biomedical research process and product development process that are holding back faster progress for everybody?" So we kind of stipulate that science is hard and it's unpredictable. There are good reasons why things can move slowly sometimes, but in our view and our experience in lots of research over time, there are also a lot of not so good reasons why things go slowly that have to do with human behavior and incentive systems and lack of the right kind of capital in the right place at the right time.

These are issues that really impact everybody who is working in this ecosystem, ultimately to the detriment of patients, of course. And so we devote our time to try to understand where those barriers and roadblocks are, across conditions, across stakeholders, and then try to bring people together to tackle or solve some of those problems.

+ 00:27:09 - Count Me In: Corrie Painter

Lisa Laudico:

Here's Corrie Painter.

Corrie Painter:

I'm the deputy director of Count Me In, out of the Broad Institute of MIT and Harvard. I'm also about 11 years out from a diagnosis of angiosarcoma, breast angiosarcoma, and subsequently the president of a nonprofit called angiosarcoma awareness.

Lisa Laudico:

So you've been a patient and also a researcher. How does that patient experience impact your researcher life?

Corrie Painter:

When I was diagnosed with cancer, it changed everything. I know a lot of people who talk about how cancer doesn't define them and I'm in just the opposite camp. I'm not trying to say one is better than the other, but cancer defines everything I do and everything I am. I changed my entire career as a result of my diagnosis and live and breathe every second of every day to the end trying to help people manage this entire experience, whether it's individual one-to-one peer advocacy or trying to develop large-scale genomics research studies and everything in between. It's been incredibly difficult, incredibly sad, and incredibly rewarding all at the same time.

Lisa Laudico:

Why don't you describe the Count Me In project and how it started and how you see it making a difference in cancer research.

Corrie Painter:

The cancer that I have is exceedingly rare, only about 300 people a year get this disease, and there's no standard of care. And doctors don't even know what to look for when they perform scans or images. It really boils down to not having a clue what steps to take, because there's no data. When you're a scientist and you're faced with something like that, it's just unconscionable. It's all awful, but how do you actually make an informed decision if there's no data to guide that next step? So it really gave me a crash course into what kind of data you need and what you would need in order to not just make your own decisions for your own healthcare. I was absolutely desperate to make some type of change or impact for the better before I succumb to my disease, and it was not thought that I would be alive for more than six months after this diagnosis. I just wanted to do whatever I could and whatever time I had to make a difference, and I saw this opportunity at the Brood Institute of MIT and Harvard, where they just, they felt the same way. These are the smartest people in the world, the smartest cancer researchers I've ever met, that look at each other every day and say, "what else can we do?" Because it's not happening fast enough. And it never will if we continue doing things in this way. One discovery at a time and the tip of the iceberg published and then everything else just siloed away. Just, it's not working. People are dying.

And long before I joined for many years, the leaders of the Broad Institute, Eric Lander, who's now, an advisor to president Biden and Todd Golub, who's now the director of the Broad would sit around talking about this issue, what can we do and what should we do? And it occurred to them that, the people who are left out of the equation are the cancer patients themselves. And the cancer patients are the passive recipients of care and decisions made by a lot of people, without actually talking to them. And so they thought they had just turned it on its head and they said, what would happen if we deeply involve cancer patients in every aspect of the research? What if we co-designed cancer research studies with patients themselves? What if we brought them behind the curtain and showed them what data we wanted, why we wanted it, how we want to generate it, how we want to do our outreach and had them partner with us in order to build it out in a way that would resonate within their own patient communities.

And so that's really behind what the Count Me In initiative is. It's a patient partner, genomic study, or series of studies where we work directly with patients that are impacted by the disease that they have. And we started with metastatic breast cancer in order to build websites and material and data and messaging that would resonate within the metastatic breast cancer patient population. There's a series of projects now. So we have six of these patient partnered projects. The MBC project was the first of these and we launched the project in, october of 2015, and we had no idea what the response would be, even though we had worked with, dozens of patients with MBC in order to build and launch this.

When we launched, we had this incredible influx of patients that joined. We had 800 people that joined and we were like, Oh my goodness, this is just incredible. This is one of the largest databases of metastatic breast cancer patients that's ever been assembled. And we have no idea where this will go, but even if we stop the study within that first year, an incredible amount of information could be unlocked by the potential that all of these patients brought together. So it leveled out. If you fast forward to today, we have over 6,000 people from all 50 States, all provinces of Canada who have joined. And they've said, count me in, I want to be part of this. And I want my data, my legacy to go toward, somebody else not having to walk down this awful path that I've gone down.

And I think that's where we meet. We want to be able to generate the data and just give it away. We haven't published a paper yet, but there has been over 30 other groups that have taken our data made discoveries and published them on metastatic breast cancer as a result of generating data and putting it out there. And I think that is a lot more than what one lab could do in the same amount of time.

Lisa Laudico:

Tell me about is this a longitudinal study that you are conducting at the Broad Institute based on count me in data.

Corrie Painter:

Anybody who's ever been diagnosed with metastatic breast cancer can join the metastatic breast cancer project if they live in the United States or Canada. And they can go to our website at mbcproject.org and click count me in. There are a couple of questions that we ask about your experience with metastatic breast cancer, and you'll be presented with a consent form, and the will talk about all of the risks and the benefits, and it will really describe in detail what the study is. The basic consent will enable us to collect copies of medical records from all the places that you told us you've been treated. And also for us to be able to send a kit with a saliva collection vial. We also have an opt in to collect leftover archival tissue. So we like to try to get the tissue in and get it sequenced and try to understand what's going on the tumor DNA. We also have an opt-in for collection of the blood sample. The blood sample can be used for us to get normal DNA from the white blood cells. But there's this phenomenon where sometimes in cancer patients, the tumors themselves will shed DNA and that DNA will live in the plasma of your blood. It's just, part of the clearance mechanism. And so we can take some of the blood and actually do genomic sequencing of people's tumors from the DNA that's just floating in their blood. Which is really remarkable, so we can get a snapshot of, what is going on in somebody's tumor samples without actually having to do any type of biopsy or resection, which is really awesome.

Lisa Laudico:

Do the patients get the results of the DNA sequencing, the genomic testing that you're talking about?

Corrie Painter:

If people want genomic information to guide their clinical care, best thing you can do is talk to your doctor about that because there are services out there. There's a bunch of services out there. And I like to make sure that folks are aware of that before they take any steps with research.

+ 00:34:45 - Christine Hodgdon: GRASP and Stormriders.org

Lisa Laudico:

We then asked Christine Hodgdon of GRASP and stormriders.org what her assessment was of the current clinical trial landscape.

Christine Hodgdon:

I want there to be another Herceptin for all the subtypes and what's very frustrating for me. I'm both grateful and frustrated is that all the research I see, it's all more HER2. And I'm like, get over HER2. We have plenty of options. There's people who need more options, stop it. And what I've heard, from science, from people who give you the inside scoop, is it's an easy target. You're going to have a good therapeutic, if you're targeting HER2. CDK is also another good target. It's very frustrating. I'm reviewing grants right now. That's the same thing. It's just like HER2, metastatic, HER2, and I'm just like, I'm over it. And I'm a HER2 patient. So I can see that, I feel like I have a lot of clout when I can say look. I'm on Herceptin, I'm on my first line of treatment and I've had no problems. But I do think that, sadly triple negative still has the least amount of research. So we still have options with hormone receptor positive.

Jim Kremens:

So this is risk aversion, and it has to do with incentives. Pharma companies simply lose money on high risk propositions. So they revisit successes hoping to find new advantages, but more importantly, decreasing the chance that they'll lose money in the process. How to fix that problem? That's a tough one. You need to change the incentive structure of the system.

Lisa Laudico:

Thanks for that, Christine. So what do you recommend as trusted resources or websites for our listeners looking for clinical trials.

Christine Hodgdon:

So I think that we can offer some trusted resources. And for me, that would be my website. I don't mean to be promoting myself, but I do a lot with trials, and I take it very seriously and I care a lot about it. And so it is a trusted source, but between my website and breastcancertrials.org, we are working together. So I constantly am telling you because I can't possibly do all of the trials. I was doing all the trials and then I was just exhausted. And so what happened was they catch the majority of the metastatic breast cancer trials. I'm catching trials that are, advanced, solid tumor trials or more general, but could still be very impactful for breast cancer patients.

I also find trials that are focused on metastases like a brain metastasis or spinal metastasis liver, these kinds, which, because it can apply to any cancer, it doesn't show up in the metastatic breast cancer trials search because they're looking specifically for MBC. So this is why I feel like the advocate voice is very important because I was able to say to them, Hey, you're missing trials, let's work together. And they were like, great. And so now they get the majority of the trials, but I'm getting these obscure less understood maybe not intuitively for breast cancer, but actually many breast cancer patients could qualify. So I think those are two sources.

We also have a Facebook page called MBC trial and innovations. It was actually started by Marina Kaplan. So yeah, dear friends and also a very savvy advocate who was also on I think over a dozen trials. She started it, she added me, made me an admin and. So now I'm me and Kelly Shanahan are the two admins of the group, and there's a of information in that group. There are doctors in that group that can comment on things. People share their experiences on a trial. They can talk about side effects that they may have had on a trial. So it's. It's pretty good. I, and I hope to get more involved in it. I've just been really busy, so I'm like hoping to do more, but these are a few trusted resources. Twitter, again, I always pushed like Twitter and making sure that you're following.

We have some of the top clinicians in the world on Twitter, like talking about trials or promoting trials. I just promoted a trial from Hopkins. That's a decentralized trial for people with a bit of a rare mutation, but if they have it right. They can still stay in their local clinic, not have to travel with the Hopkins. That's why it's decentralized. And their oncologist can prescribe an off-label. A therapy drug. And if they have this mutation, so these are a few resources that now there's a lot of stuff on Twitter that you probably can't trust, but I think you've got to follow. And we could maybe provide a list of influencers either as scientists, clinicians, researchers, and advocates so that people know who to follow. Cause it can be a little bit overwhelming.

Lisa Laudico:

Yes, we have your comprehensive list of who to follow Christine included in our episode notes. Thank you so much for that.

Christine Hodgdon:

I had a doctorate at Penn tell me that this patient I was working with had no actual mutations. I'm like there are trials, maybe not at Pennsylvania. So this is a big problem, too. A lot of doctors are promoting trials from their own institution. So when you hear no actionable mutations, they might be saying there's no actual mutations for trials that are being conducted here in our institution, which is almost like a lie by omission because there are trials and, if you are willing to travel, that increases the chances you can get on one of these trials.

Me personally, I want to change that clinical trials.gov website. I just hate it. It is unwieldy. It was never intended for patients to use. It was intended to just register trials, but unfortunately that's where everybody registers their trials. But a lot of times the trials are not updated, like a lot of times trials will say they're recruiting, they're actually not recruiting. And so you'll see a Dana-Farber and Sloan, Kettering, and MD Anderson. They have their own webpage with their own trials, which is not a very great way - it's like for patients it's not the best way of finding trials. Like some people are willing to travel anywhere. And I was recently told, I didn't know, this, that Southwest will fly patients for free if they're getting treatment.

+ 00:40:16 - Lianne Kraemer - Metastatic Breast Cancer Alliance (MBCA)

Lisa Laudico:

Next up, we spoke with Lianne Kraemer from the Metastatic Breast Cancer Alliance's initiative on clinical trials and brain Mets The MBCA is a national umbrella organization for all nonprofits and industry organizations who work in the MBC space along with patient advocates who work to improve outcomes for fellow patients. Here is patient advocate, Lianne Kraemer again.

Lianne Kraemer:

The reason it was started, was, the problem of getting access to trials has been a known problem in the research community of physicians and amongst patients for a long time. And there was this specific woman, Marina Kaplan, who just, it's hard to talk about her, cause she's just wonderful. She was brilliant. I had a really wonderful experience with her real quick. I'll share. I was at a conference when I very first met her and had just started an IV chemo and was having some side effects and it was actually bruising and we all bruise right.

I was getting these massive bruises and it's weird. You get so used to things like you, just things that would have sent you straight to the emergency room prior to cancer, make you go yeah what, so I'm, so w this is happening, and I was seeing these bruises, like the size of a grapefruit, but everybody's yeah, yeah we bruise. And she looked at me, and she's like "what drug are you on?" And I told her, and she goes, you need to call your oncologist right now. And I was like, really? And it was a low platelet issue, which can be really serious. You need platelets to clot. And so she was so mothering to me and cared so much. She just, like I never knew what was going on in her life, how bad her cancer was. It actually took me surprise because she was always after that moment, like sending me instant messages or saying, how are you doing what's going on? And just so wonderful. That's just one little story.

She just was amazing. And she kept herself going through clinical trials. She was triple negative which has a poor prognosis. And she found herself clinical trial after clinical trial to keep herself going. She lived, I think, five years. And in the end she got brain metastasis and could not get on a clinical trial because of brain metastasis. And she ended up passing away.

Lisa Laudico:

Not from brain Mets. She did not die from brain Mets.

Lianne Kraemer:

No, it wasn't the brain mets, it was the liver. So that's the other thing, sometimes like these brain mets that you have can be treated in a different way and you need that clinical trial for your body. So it's not just looking at the clinical trial from a standpoint of treating brain mets. She needed a clinical trial cause she was out of treatments that were any good. And she needed it for her body, not her brain, but she couldn't get into that clinical trial because she had brain metastasis. We were already working on this issue, she was part of the group.

Jim Kremens:

Marina couldn't get into any clinical trials to attempt to stop her liver cancer because she had brain Mets. There's no guarantee that any of those trials would have made a difference, of course, but it's unsettling she didn't have the option. We've talked about clinical trial exclusion criteria and how scientists are starting to reevaluate these practices. Marina's story is the dark side of clinical trial design rigor.

Lianne Kraemer:

And so when she passed away, it was the fire under our rears. The project is named after Marina Kaplan in her honor. And her picture is with it on the website. And it's, that picture was actually taken - If people have a chance to go look at the Marina Kaplan project on the MBC Alliance page - that picture was taken five weeks or six weeks before she passed away. And so I think that's something that would be nice for the average person to see is that you can look completely normal and be extremely sick. But that's another discussion.

Lisa Laudico:

I appreciate your work on the initiative at the Alliance level, because I think it's part of the puzzle. And then there's these other issues around clinical trials that I think together with these COVID silver linings elements that maybe we can see some real positive change.

Lianne Kraemer:

I really hope so because I just, I want more people to have access to clinical trials. I want more people to get what I got. I got some great drugs. I should mention the third clinical trial did not work at all for me. And I felt so guilty about that. My oncologist had done all this work and Oh my gosh, it didn't work. It didn't work at all. And I didn't expect to have all this guilt I did. And one of the most amazing things, and I don't know if it was her that said it to me or who said it to me, but when a drug fails, you learning still occurs. And even though you didn't benefit from that drug, the doctors are still, and researchers are still going to learn something from your experience on it, whether it worked for you for a year or it didn't work at all. Still a learning experience. And that's important to remember as disappointing as it was to me. It was like, A light bulb.

Lisa Laudico:

Do you think that would be possible for a new category of clinical trial participants who don't really match the ideal candidate? Which is a lot of metastatic breast cancer patients, let's be clear. But who might provide the researchers with useful data nonetheless, and who are interested in the trial because they don't have many or any other options.

Lianne Kraemer:

Certainly think so. It's a matter of whether they're willing to do it because there is room for them to do a subgroup, say for brain metastasis, phase one, a subgroup where you have some people with brain metastasis and you don't see activity in it, then you have answered your question and you can move on and phase two and not include them. So I think there's a place for that. That's what I hope to see happen eventually with brain mets and other things that make the exclusion, a subgroup for people who have had a ton of other treatments. I know that's possible for them to do. Whether they will do that, that's up to them. Unfortunately, we can push and we will push. Which is what we're doing, but absolutely.

Lisa Laudico:

Corrie Painter had the same idea.

Corrie Painter:

My take is that you have to get trials designed with very narrow kind of parameters in order to see if there's any signal. And so if you don't constrain your central theme and who you're letting in, you won't know if it's working or not, or was it the brain met, did that cause there not to be response. And so I think that you have to design trials to just be more nimble, say. Here's the central tenant for me to see a signal. And then here is the wider net of every single person that wants to be on this trial. And I will be able to learn from everybody, but this is the stuff that's going to lead to whether this gets approved or not in this indication. And then let's still let everybody in and let's still collect everything from everybody else as well. It will be counted in a different way than these central people. And again, I'm just making something up here, but I think if you could design a trial that way you could get real-world evidence because ultimately what are you going to do? You're going to approve a drug based on these people, and then you're going to give it to everybody. So why not just do it all at the same time?

Lisa Laudico:

And yet it's back to the money equation. That wider umbrella means that trial design is more expensive,

Corrie Painter:

Too bad. That's where pharma needs to pony up. Sorry, like I said, we have unpopular positions, but that's where pharma needs to pony up.

+ 00:47:55 - PAIR: Deb Collyar

Lisa Laudico:

Unpopular or not, it sounds reasonable to our ears, and we get that there are some current realities in the research landscape that are also factors - publish or perish, return on investment, boards of pharmas demanding results. But we also spoke with Deb Collyar who has spent many years looking into these very issues and asked how public policy changes can help move the needle.

Deb Collyar:

Hi, I'm Deb Collyar, and I'm president of patient advocates in research, which is commonly known as PAIR for short. I was diagnosed with my first breast cancer at age 32 while I was an executive in a computer company. And that ended up being a stage three C and we knew that at the time, what we didn't know at the time was that it was triple negative breast cancer. And that's because TMBC, hadn't even been identified yet.

And so when we found out how little was actually known about breast cancer at that time, and how little had changed in like 30 years from before I had been diagnosed, we became passionate in wanting to help make changes so that people wouldn't have to go through this. And frankly, at that time I didn't have a child, but we didn't want that generation to have to deal with this. So we attended the first mother's day rally in Sacramento and met the founder of breast cancer action at the time. And she made my husband a board member first, and then me, which was unusual.

After that, there were lots of things, basically in a five-year period, chemo induced menopause, a baby, that was a surprise, getting laid off even though there were anti-discrimination laws for cancer patients, it doesn't really matter, and the second primary. All of those events happening quickly really solidified the vision and determination to improve results for patients.

I got involved in breast cancer, patient advocacy, and went through all of the different, more traditional kinds of patient advocacy, which includes, direct patient support legislative and lobbying fundraising, and even got involved in what I've labeled watchdog advocacy, because we learned from the AIDS movement especially here in San Francisco how to bring issues to the table that needed to be addressed.

But in a different way than AIDS was doing sometimes. But we figured out that really wasn't enough and what didn't exist was patient advocacy in the research setting. And it became really clear. The more we learned and we read like crazy, all sorts of verticals like most of us do when we get involved in this. That we needed to change both the mindset of the researchers doing the work, as well as the system of the research. It's called a research system, but it really isn't, it's this discombobulated mess that really could be streamlined to create better answers, whether that's a drug or a device or whatever it is for patients.

And I started to focus then in that way and change the way that the whole thing worked. I guess part of that came from my background, which is really in everything from communication and strategy and training to operations to help develop research patient advocacy. And we're really translators in both directions is the way I think about it. PAIR was founded in 1996 as an informal international communication network for patient advocates whether they're independent patient advocates or they're a part of another organization mostly in cancers, but not only, there are other diseases as well.

And what we're trying to do, really, it was started to help build research, patient advocates and advocacy and learn from one another. So as we did that as translators, we get involved in research discussions hopefully as early as possible and all the way through to bring the patient experience and voice and input in. But we also learn what's happening in research and try to translate that out to patient communities and the public and find out where the issues are. So we can actually become problem solvers and try to help resolve barriers and streamline that process.

So that's a lot of what we do, it would be important for me to say what type of research we're talking about and it's really broad, right? So it's everything that could actually touch a patient, which includes translational research, which is basic to clinical, preclinical, clinical research, epidemiology, and even healthcare delivery research. So we really cover the gamut there. I've learned a ton obviously, and continue to from everyone, both patient advocates and researchers and patients that we're continually talking to and learning from as well.

But one of the things about research that I learned quickly is that researchers didn't know how to talk to us because they didn't even know how to talk to each other. Everyone has their own lab speak or what we call med speak, or something like that. And so the way that I've explained that is that their careers are rewarded for becoming experts in smaller and smaller pieces of things. So for example, they become the expert in the letter K. And they can tell us about the letter K from every dimension, but forget sometimes that's only one letter in the alphabet.

And as patients and advocates, we have to put lots of alphabets together, not just the English alphabet, but all sorts of them to really put a whole life package back together again, because we have so many different elements. And we bring those life skills and experiences and problem solving skills to offer new approaches, to a very narrow way of thinking about what's acceptable in the research world.

Jim Kremens:

This is a big thing too researchers are actually encouraged to use as much jargon as possible in papers, which makes papers extremely difficult to read for everyone, including other researchers. This is an information science issue. Journals actually reject articles for insufficient jargon. To put it gently researchers, at least pre COVID often seem to be more interested in staking their claims in a way that would prevent others from following them than in a way that would enable them to follow. Which of course, isn't very collaborative. We're seeing changes with COVID though, which will hopefully stick.

Deb Collyar:

There is a lot of stuff with emerging research that comes out that nobody knows how to handle. And so we're always focused on, okay, what does this mean for patients? What are the issues that are going to maybe not be here today, but are going to come up from that in the next few years that we really need to start making sure everybody knows about now.

I guess the thing that is important to me is how to merge the traditional research pieces together in a way that emulates what actually happens in the human body, so that were looking at something that actually is relevant. We're constantly trying to help keep researchers focused on what is relevant for treating patients, not for this cool science idea over here that could lead to gosh, we cure it all these mice while yeah.

We've been doing that for decades. Let's think about what does that mean for humans then? And it's not that researchers don't do that. It's just that. The system has not been set up well. Within a company, they have their own research process, but I have actually found out that it's not as smooth as we all think it is. There are silos, major silos, there. Let alone, when you start to talk about, different academia groups, different consortia, clinical trial groups and all of that. That's really important for us to have a voice in there and say, Hey, yoohoo what about this over here?

And then of course, the most important question we ever ask, and when all else fails, you can always say why are you doing it that way? Or why are we studying this? What are we really trying to get out of this? Because so often it's just like any field, right? Any career that anybody ever has, you get that tunnel vision where this is what you know, day in and day out. And so you forget that there's a bigger purpose here. You get involved in the daily workflow.

We work on lots of different levels on policy, on actual individual projects and programs. And allow researchers to try to do things in new ways. That includes building some unique collaborations, and really helping them focus. One of the things is to say what if we pilot this in metastatic breast cancer for example? Why don't we pilot some of these ideas so that we can learn from them, see what works, what doesn't work. And then we can revise policies and processes along the way, because that's the whole key, right?

You can't just put legislation together for instance, and think that you've won because you get it passed through Congress or whatever. Which is really hard work, and really important work, but that's not the end. That's sometimes the beginning, what we have to do then is get it implemented into institutions which are major problems for us into companies, into research processes and frankly, daily workflows for clinical sites. As well as bringing in, then the whole idea of patient engagement and input and all of that.

So it's a lot. It sounds daunting when you get into it. My problem is focus. I'm a connector, right? A translator connector. And so everything to me seems like it's connected together, which is why it's also really important to have us all working together. I don't need to be an expert in all of this stuff and do it all myself. That's why I formed PAIR. So we would have a broader network and bring in more people on a regular basis who then can specialize in certain areas if they want to. And then, those of us that opened the door into a new area can backfill with really good qualified people.

Jim Kremens:

This is so important. There's an organization that's trying to help researchers work together more harmoniously. PAIR is like a conductor for the orchestra, but the orchestra is still too large for pair to conduct. PAIR, or something like, it should be more broadly funded. The concept that the free market is the best path to success hasn't necessarily panned out so well with regard to scientific research. It's the reason that the dreaded silos exist in the first place. We aren't going to get rid of the free market, of course. But putting a traffic cop in the middle of the circle seems like common sense.

+ 00:58:12 - Experts discuss what the research space looks like.

Sarah Mann:

As we have established, a lot of the information about clinical trials can be inaccessible. We asked Dr. Fischbach how he stays current with all the latest science.

Dr. Neil Fischbach:

I think the reason that most people are drawn to oncology general is that the field is continuously changing. That the integration technology is what again, attracts us all in the rapid pace of development. So I think that most people can be comfortable that their medical breast oncologist is conscious of what's available in the research world, is looking out for them as a partner an advocate to try and connect them with research opportunities if there are any really compelling ones around. And that's something that every person living with breast cancer should be very comfortable asking their doc is it time, for me to be part of clinical trial, what clinical trials are you evaluating? How are you learning about this stuff?

I think what varies with a community practitioner, depending on the practice. There are some practices which have really prioritized clinical research and have very developed clinical trials programs. And then there are some private practices, generally smaller that may not have the resources to fund that kind of effort. And in that case, going to another institution or large academic institution is a really invaluable way to get access to that institution's clinical trial pipeline, and also learn a bit about what's available nationally, but even, coming to Yale to see a Yale breast oncologist you may not learn about what's available at stone Kettering or Dana Farber. Or what's available around the country. And I think it's very similar portfolio at big academic institutions, but still it's remains a challenge.

Lisa Laudico:

We asked Kristin Schneeman whether there was any one entity or place that synthesized all of this information from different companies, universities, or research centers.

Kristin Schneeman:

I don't think so. Not that I'm aware that there's the global brain of medical research that is easily accessible to the lay person. Because I think some of these knowledge bases are behind paywalls or behind closed doors, corporate doors. But there have been some kind of high profile. Flame outs on that front with IBM Watson, trying to process or synthesize the universe of knowledge in all of the academic journals to speed up research. That didn't go so well. But, I know that there have been a lot of other efforts on that front, but it would be accurate to say that there's unfortunately not a global brain that we can tap into, unfortunately yet.

Another great role for patient advocacy organizations and, I know many organizations do this, is to be the collector and interpreter of all of that medical information and research information for their communities. So again, not to put everything back on the patient advocates, but I do think that many of those communities have played a really important role in trying to synthesize and even honestly for the research community sometimes, BP, the hub of information and knowledge and their disease area and make sure everybody knows what everybody else is doing, but then all the communicated with their patient communities and plain English.

Jim Kremens:

Returning to Dr. Fischbach we asked him about which trials he finds really exciting in the metastatic breast cancer space.

Dr. Neil Fischbach:

I think that's a little bit different for different subsets of metastatic breast cancer. And I think in the Princeton, the triple negative estrogen progesterone and her two negative breast cancer setting, I think there's a lot of really fascinating stuff going on in immune therapy, increasing immunogenicity of tumors cell based therapies. In estrogen dependent breast cancers, I think some of the most exciting trials may be the least sexy is restoring estrogen sensitivity, prolonging the period of time that anti-estrogen therapies will work identifying parallel growth pathways that intersect with the estrogen pathway. And then in the HER2- positive metastatic breast cancer pathway, there's just been an explosion in novel, anti HER2 drugs.

I think that the subset that most people are interested in because it has just the most allure is the idea of immune therapy both simple immune therapies, like the Opdivo's and Kaytruda is that we see advertised on TV and getting to the most sophisticated cutting edge immune therapies which will be tumor-infiltrating lymphocytes and engineered T-cells reinfused in people to fight cancer cells. So the waterfront is really exciting. And I think that the next big advances, though I think are gonna come incrementally, as I said, I think with triple negative breast cancer, I think we'll make some immune therapy advances with ER, estrogen dependent, breast cancers in the estrogen pathway, restoring estrogen sensitivity, and the, her two looks like the next leaps are going to be in just improving our targeting of the, her two pathway.

Lisa Laudico:

So there's this whole thing called ELI5 which explain like I'm five years old.

Dr. Neil Fischbach:

So ELI5 style. The first breakthrough really in immune therapy for cancer was understanding, how do cancers turn off the immune system? So this was something that was theorized for a long time for a cancer to grow. It must somehow truly your own body's immune system or else we get rid of it. And we never really understood exactly what those pathways were. So roughly 20 years ago or more, we discovered two key pathways. One called the PD-L1 pathway and other called the CTLA four pathway. It turns out that cancer cells make stuff that binds to receptors on your immune cells and turns them off and probably not just on the immune cells, probably on a lot of cells in the environment around a cancer.

It's the cancers forcefield and the next step was developing drugs. That block that interaction, that prevent the cancer cells stuff from binding to the immune cell and turning immune cell off. And that's exactly what Tecentirq does and Opdivo and Keytruda, this kind of burst family, what are called immune checkpoint inhibitors that block and release this break on the immune system. And the cancer that people thought was least likely to have any impact on immune system, lung cancer was the first really tremendous success for this strategy. But across a wide variety of tumors that works. So that's the checkpoint inhibitor pathway for some types of cancer though, this simply does not have any impact.

And unfortunately, estrogen receptor, positive breast cancer, the most prevalent kind of metastatic breast cancer does not respond to these treatments. So why is it that estrogen receptor positive breast cancer creates an environment like if you will, in immune desert as opposed to a very responsive environment. And there are tremendous strides being made in, trying to converse in a new desert, into an immune reactive environment. If the Israelis can grow vegetables in the desert, we will figure it out how to make a, desert environment, more amenable to this type of checkpoint inhibitor. So that's one branch.

Another kind of very exciting immune therapy is re-engineering our body's own T cells, our immune effector cells to fight cancer. So our immune system has two main forces, if you will, to fight cancer. One is cell based. Cells like T cells and NK cells, which directly can kill cancer cells. And then we have what's called a humoral immunity, which are mainly proteins, antibodies, which bind to infectious organisms and mark them for clearance from the circulation and can also bind to cells that are infected and even cancer cells and mark them for disposal, if you will.

One cell is the T-cell and there's a technology where we can just from your own peripheral blood isolate T cells, and we can reprogram these T-cells to fight your own cancer cells. Now critical in that process is the cancer cells have to have a target on it that's unique relatively to the cancer cell or not to your healthy tissues. So the soldiers that we're putting in your body don't cause damage and turns out that the disease, which is most amenable to this has been lymphomas and leukemias cause B-cell lymphomas and leukemia all expressed on their surface and ideal, unique target. That's not so important from the rest of the body. And we can engineer T cells against this target, which is CD 19. And that has cured very resistant lymphomas leukemias.

So taking it full circle, we said that one of the early vignettes, how do people find out about clinical trials? God, 10 years ago, a person who I cared for who had very resistant lymphoma, had been through about five lines of chemo, had been through a autologous bone marrow transplant, very high dose chemotherapy, and his cancer was growing again and he brought in this newspaper clipping to me from like back page signs, times of New York times about this technology where they were taking these immune cells out of people and engineering or reinfusing them and there had been two people who had a great response and he gave me the article and I said, gee, that looks interesting. And we contacted the PI and he's like well send him down. And he became one of the first 10 people involved in the definitive clinical trial of anti CD, 19 car T cells from lymphoma and his lymphoma has been cured. it doesn't take Watson or IBM sometimes it just takes, again, collaboration between someone living with cancer and their doc. I heard about this, let's check it out. But nonetheless, this CD 19 car T cell works like gangbusters for cancers that have CD 19. And we are slowly trying to identify other suitable targets on solid tumors. So there are potential targets in breast cancer, pancreas cancer, lung cancer. And every major institution is really ramping up their car T cell programs.

And as a newer modification of that there are two other cell based therapies to talk about. One is the natural killer cell, which is a cousin of the T-cell and that has some particularly advantages over car T cells. So that is a newer but rapidly accelerating field. And the last, which is in my mind, even idiot simple is this idea of tumor infiltrating lymphocytes. When you look inside a cancer, you may find some immune cells there. And the idea is while they're there, they must be doing something. They must be fighting cancer and if we could suck out those cells expand them a few billion fold and then put them back into the person. Might that be an effective anti-cancer strategy? And that actually does appear to be effective in some cancers. There's one very prominent and publicized case of a woman with metastatic breast cancer that's benefited from tumor-infiltrating lymphocytes therapy.

And question now is. How do we make it work for everybody? How do we easily extract tumor-infiltrating lymphocytes? What's the best way to expand these cells outside of people and make them even more effective.

Lisa Laudico:

I know that particular case that you're talking about, it was an incredibly successful but also exorbitant. It costs so much money, for one patient's response. Are you aware of work being done to try to reduce the cost of such a treatment?

Dr. Neil Fischbach:

I think this is where we are going to have to rely on politics and regulation because we live in a free market world and the drug manufacturer can say to me, a life is worth $2.5 million. And these new car T cell therapies have price tags that are getting to approach that when you add in all the care, that's involved, not just getting the product, and this is going to be a real issue for us as these products expand in their applicability to large group of people the laws of supply and demand have not applied to medical devices and drugs. And we really need to think about that.

+ 01:10:24 - Policy

Lisa Laudico:

What are the smartest things that policy makers can do to cure cancer faster? How should local and state governments and Washington spend their money? What are they currently doing wrong?

Kristin Schneeman:

I will say that a very good place to start is asking patients. And we don't want to make patients responsible for fixing all of the systemic problems that are impacting them. But we've definitely been very vocal advocates for a long time with engaging patients and their patient organizations as well. Because individual patients often don't have the time or the inclination or the bandwidth to participate in the process overall. But there are a lot of patient organizations out there now that are very engaged at much earlier stages, and there's much more of a movement to bring patients in their representatives into conversations about, for instance the design of a particular trial.

What are you even studying? Does it even, is it something that really matters to patients? Let's talk to patients when we're setting the research agenda and when we're figuring out, which questions are most important to ask and answer. Talk to patients when we're designing the trials that we make sure that we're designing them in ways that are going to attract patients to participate and to stick with it and are going to produce outcomes and measurements that are meaningful to patients. Let's make sure FDA is evaluating those products based on measures that are meaningful to patients and not things that are easy to measure and, are just advantageous for the sponsors. So I think that starting with patient engagement and engaging patients perspective from the very earliest stages is a good place to start.

That is a discipline that I think is starting to take hold in companies more over the last handful of years. the past, I think they mostly treated patients as consumers of their products. And they engaged with patients on the marketing end. But frankly, patients often aren't even really the customer. So it's often the providers or the insurance companies that they're dealing with and not even the patients. But they have become increasingly interested in how they can engage patients, earlier in their stages of development and, you see the evidence of that and the fact that they've got things like chief patient officers and a lot of these biopharma companies now whose job it is to figure out how to bring that perspective across all the aspects of the operations.

A lot of that was driven by the FDA, honestly. They made it a priority half a dozen years ago when they created this patient focused drug development program at the FDA. Which said to sponsors, we expect you to engage patients in your development programs. And they have created a whole series of activities that they do at FDA to better understand what the patient's perspective on their condition and on the trial designs and on the, et cetera, et cetera, is, at FDA. Sponsors care what FDA thinks. So if FDA says something as a priority, they tend to go into it. Anyway that's one piece of it is bringing the patient's perspective because it brings a sense of urgency to the process, but it also, as I said, is likely to result in a trial that's better designed that is going to recruit better, that's going to get to an outcome that's more relevant to patients.

I do think FDA obviously has an important role to play and I've been really heartened during the COVID experience, they've just been extraordinary, right? I think everybody can perceive the fact that these people are just knocking themselves out. They are, going so far above and beyond to manage everything that's going on during COVID, along with everything else. But at the same time, they've been very proactive about what are we learning in this process? They themselves want to know. What did we do here that we think we can keep doing?

Like we know we can't all work 24 seven, but what did we do that we want to keep doing? We're engaged with them in that exercise and they are being very proactive at trying to understand okay, if we want more people to set up master protocol trials, or if we want more people to Use some of these other kind of statistical techniques, if we want people to recruit more diverse patient populations, that's also an issue that obviously came to the fore during COVID was lack of diversity and the just really terrible disparities in outcomes and in clinical trial participation in minority communities, if we want, people to recruit more ethnic and racial minorities to trials what do we need to do as FDA? What guidance do we need to provide? What incentives, what carrots do we have? What sticks do we have? So they're a key player.

I will say one thought that I have had is that, NIH funds primarily basic discovery, but they fund a lot of clinical research and clinical trials as well. And the clinical trial networks that they fund have been incredibly valuable during COVID. But I think they need to ask themselves the question about whether they're funding trials that are producing meaningful results. So the question I introduced earlier that FDA has been asking about, why are 94% of these trials not to produce evidence that it is there's going to be actionable cause they're badly designed.

If somebody goes to them asking for funding for a clinical trial, I don't think NIH has very strong criteria about what they are willing to fund and what the trial needs to look like and what the outcomes need to be to get NIH funding. So I think that NIH also has a role to play. Their criteria are fairly minimal.

Lisa Laudico:

Wow. But then on the flip side, patients complain of rigid clinical trial research nurses that I know complain about, ridiculous clinical trial design, that's so rigid, that makes completely no sense. Where it seems that's on the FDA side, not on the NIH side then.

Kristin Schneeman:

Yeah. True. And actually, just before we got on the phone, I happened to come across something that made me feel very hopeful and good. There's a group called friends of cancer research, which I'm sure you're familiar with that kind of, is some more of a policy oriented organization that crosses all the different types of cancer. That was very engaged with NIH and FDA and all of those players and they, along with ASCO, have this kind of new effort to really look at exclusion inclusion criteria and say, what are we really doing here?

What impact did these really have? Whether it's wash out periods or other medications you might have taken previously or performance status. Only high-performing patients can be in a trial. Like isn't that sort of against the point of the trial?

But anyway, so they went through a number of these and did very rigorous analyses. Cause often these types of criteria are just habit. It's It's been done before, everything is cleaner. So they are really trying to highlight this problem and bring some data to bear about whether they make sense or when they make sense. And I think FDA is very much on board with that. And they will have to follow up by acting on it when they're approving products. And when they're talking to sponsors about the trial designs, they need to be expressing it in guidance. For instance, they had guidance, not that long ago about how to get more diversity in clinical trials, which they have stated as a goal. And one of the things they highlighted was the exclusion criteria and ways in which that can really particularly disadvantage racial and ethnic minorities. One of the things they said was don't just automatically assume that the exclusion criteria for your phase two trial needs to be the same for phase three. It doesn't necessarily have to be as exclusive in phase three. So there are definitely putting out guidances that say this. The question is, are they then acting on it, in the actual product reviews, but there's hope people are focused on these problems now.

Lisa Laudico:

There is hope. I am particularly excited with the possibility of the FDA taking up the recommendations for increased clinical trial flexibility that was outlined recently in a collaboration by ASCO and the friends of cancer research. We'll need to advocate for these important innovations, of course.

We then asked Jill about any possible pathways for patients who have been excluded from clinical trials to gain access to these drugs.

+ 01:17:29 - Jill Manning: Compassionate Care

Jill Manning:

So right now we do have a pathway and this does come up fairly often for me throughout the year. And this is something I do handle at the IRB and we'll have a physician investigator who treats class of subjects, potentially for a rare disease say, and she or he is aware of a clinical trial in which a brand new investigational drug is being studied. And they really want this particular patient to get into this trial because they think that it would be a great fit. And they refer them to the PI if it's not themselves, that's running the trial. And unfortunately they do not meet inclusion or exclusion criteria, and they're out of that trial.

And that physician A still wants this drug for that patient. The pathway that we take is through compassionate use at the FDA, and similar and related to right to try, but there are a few different FDA pathways. They'll often call the IRB because the IRB is approved in this. And this is very different from research. This is important that this is an FDA pathway for clinical care, not research, to access compassionate use of an investigational drug. And we have emergency use for single patients, or we have non-emergency use for single patients. And depending on the particular clinical situation . It's a very speedy process that goes through the FDA and the IRB.

And I often guide physicians for this. In order to just treat that individual with the investigational drug that might be studied in another trial. And one of the criteria for getting that emergency use is often that they are not eligible for a research trial. And so I think that the more patients who are aware of this, I think it's really important that we empower individuals who might have rare diseases to be asking for this, particularly if they are finding that they are excluded from several trials or one trial that they're interested in.

+ 01:19:18 - Final Thoughts

Lisa Laudico:

How could trials be designed to be more patient friendly and inclusive without negatively impacting the integrity of the research. And do you see any of that happening today?

Jill Manning:

This question is so great and so important, and it brings it back to patient empowerment. And this is where I really encourage your audience and your listeners, if they are interested in getting involved in the research side of things, but perhaps not as a trial participant, excellent way is to become an IRB member, a community member of these review boards, because you have a lot of power and you have a lot of influence. In that you can be engaged in these ethical discussions. You can offer additional suggestions that would make things easier from the patient experience. And in order to make these protocols more patient friendly, we need to have patient advocates in the room.

And the review process is one side of things. Of course you could even be involved earlier in the process when partnering with an actual individual PI, principal investigator and institution, particularly for protocols that are authored by PIs. That's certainly one way to do it. But, IRBs are required, we have US federal regulations, are required to have a certain number of community members present at every meeting and IRBs across the country are always eager to have community members that reflect different patient populations to sit in and to be able to opine and offer suggestions and recommendations for how we can improve this process.

Lisa Laudico:

How do you think cancer clinical trials could be more friendly to patients?

Corrie Painter:

My work, as an advocate talking to so many metastatic breast cancer patients and patients with a variety of different cancers, there are some themes that are crystal clear. One is that patients should be involved in the design of any clinical trial that's going to impact them. Bottom line, you absolutely should never design a clinical trial and then present it to a patient or a patient population and say, what do you think?

Lisa Laudico:

So how do you deal with the emotional demands of your job?

Dr. Neil Fischbach:

Yeah I think there are two approaches to that. I think one approach is make a barrier, just be separate and you're the technician. You can't really get active and the other approach is to jump in and be part of it. And I think there are pluses and minuses to both techniques. I think I generally favor the ladder is the jumping. for me it helps deal with the tragedy of it all. If I have been intimately or is originally as I can be. Involved in participating and just refocusing what our rewards are. And sometimes the outcome with cancer is determined it's what we do along the way that makes memories and joy and positive outcomes. And so being someone who really values those kinds of impacts. As much as I value, adding time to people's lives. I think that's essentially how do it. And your doctors are socially inept people that the people will come to my door are often the people that come my best friends. Oncology, I think at its heart, I think what draws most people do, oncology is the intensity of it's the relationships you are able to form. It is being with in bearing witness to extraordinary things that can't help, but make you appreciate your own lives and experience your own life differently.

Lisa Laudico:

When my co-hosts Jim Kremens, Sarah Mann, and I began working on this project. We were interested in the question, "why hasn't breast cancer been cured?" Obviously, there is no simple answer to that one. Science takes time, and, to paraphrase Kristin Schneemann, there are some good reasons that science takes time. But there are also some not so great reasons...

In asking the same question to many of our guests, we learned that medical research doesn't proceed as smoothly as we might've thought. To paraphrase Corrie Painter, it's not happening fast enough, and people are dying. It's beyond the scope of this program to attempt to solve the ways in which the system "isn't working." Instead, we've tried to illuminate the problems, and most importantly, show that in the face of a global emergency, most of them just melted away.

So what happens next? The signs are surprisingly positive. The FDA, it seems, is genuinely trying to understand what "went right" during COVID. We sincerely hope that non-collaborative practices and various other old habits do not slip back into common usage, but hope is not enough.

Lives are at stake. The manner in which medical research is designed and how the results are shared really matters and will genuinely impact how many of those lives can be saved. If we, as a community, can understand and advocate for best practices in cancer research and trial design, the cure might come sooner than we think.

We are also releasing an additional episode with a complete interview with Judy Perkins, who, in 2015, became the first MBC patient to be declared free of disease after a course of immunotherapy using tumor infiltrating lymphocytes. Judy spoke with co-host Victoria Goldberg about her various experiences with clinical trials and standard treatments.

We'll also be releasing new content, giving more information about MBC connect, and our April lineup will also explore issues impacting the Latin X community living with MBC and policy and legislative advocacy. This is especially important with the opportunity of the new Congress. Later in the month, we are really excited to highlight the new BECOME project, which stands for Black Experience of Clinical Trials and Opportunities for Meaningful Engagement.

BECOME is a new research initiative designed to find solutions within the black community. It is using real life, patient input to identify practical ways to make it easier for black people living with MBC to take part in research trials.

This podcast is produced by me, Lisa Laudico and our truly amazing team of Bob DeVito, Dar Finkelstein, Natalia Green, Victoria Goldberg, Ellen Landsberger, Sheila McGlown, Reilly Starr and Anne Woodward. Our executive producer is Christine Benjamin, senior director of patient services and education at SHARE cancer support. Our senior intern is Sarah Mann, along with interns, Angelica Alberstadt, Emily Lewis, Samantha Silverstein, and Amy Tedeschi. We have benefited from expert social media consulting from Jake Amorelli and sound design and original music compositions from Jim Kremens. You can find more episodes of Our MBC Life, wherever you get your podcasts. Be sure to subscribe, rate and review us and look for a new episode every other Monday, check out our blog and full episode notes on our website@ourMBClife.org. We would love to hear from you.

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