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ASCO in Action Podcast

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The ASCO in Action Podcast provides analysis and commentary on cancer policy and practice issues. The podcast is hosted by Dr. Clifford Hudis, CEO of the American Society of Clinical Oncology. ASCO in Action, the society’s internal wire-service, provides the latest news and analysis related to cancer policy. These updates provide snapshots of ASCO’s ongoing advocacy efforts, as well as opportunities for ASCO members and guests to take action on critical issues affecting the cancer community. Music provided by gmz, via ccmixter.org.

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The ASCO in Action Podcast provides analysis and commentary on cancer policy and practice issues. The podcast is hosted by Dr. Clifford Hudis, CEO of the American Society of Clinical Oncology. ASCO in Action, the society’s internal wire-service, provides the latest news and analysis related to cancer policy. These updates provide snapshots of ASCO’s ongoing advocacy efforts, as well as opportunities for ASCO members and guests to take action on critical issues affecting the cancer community. Music provided by gmz, via ccmixter.org.

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iTunes Ratings

6 Ratings
Average Ratings
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Cover image of ASCO in Action Podcast

ASCO in Action Podcast

Updated 11 days ago

Read more

The ASCO in Action Podcast provides analysis and commentary on cancer policy and practice issues. The podcast is hosted by Dr. Clifford Hudis, CEO of the American Society of Clinical Oncology. ASCO in Action, the society’s internal wire-service, provides the latest news and analysis related to cancer policy. These updates provide snapshots of ASCO’s ongoing advocacy efforts, as well as opportunities for ASCO members and guests to take action on critical issues affecting the cancer community. Music provided by gmz, via ccmixter.org.

ACS CAN President Lisa Lacasse Discusses Advocacy Priorities, Partnership with ASCO

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Lisa Lacasse, president of the American Cancer Society Cancer Advocacy Network, speaks passionately about the critical importance of advocacy and ACS CAN’s partnership with ASCO in reducing the cancer burden, in latest AiA podcast with host ASCO CEO Dr. Clifford Hudis.

Find all of ASCO's podcasts at podcast.asco.org

TRANSCRIPT

Ad: Hi. My name is Shannon McKernin. And I am the host of the ASCO Guidelines Podcast Series. When a new ASCO guideline publishes, we release a podcast episode featuring an interview with one or more expert panel members. Each episode highlights the key recommendations and the implications for patients and providers. You can find the ASCO Guidelines Podcast Series on Apple Podcasts or wherever you're listening to this show. And you can find all nine of ASCO's podcasts, which cover a wide range of educational and scientific content, and offer enriching insight into the world of cancer care at podcast.asco.org.

Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

Clifford Hudis: Welcome to this ASCO in Action Podcast, brought to you by the ASCO Podcast Network, a collection of nine programs covering a range of educational and scientific content and offering enriching insights into the world of cancer care. You can find all of the shows, including this one, at podcast.asco.org. This ASCO in Action Podcast is ASCO's podcast series where we explore policy and practice issues that impact oncologists, the entire cancer care delivery team, and the individuals we care for-- people with cancer. My name is Clifford Hudis. And I'm the CEO of ASCO, as well as the host of the ASCO in Action Podcast series. For today's podcast, I am really pleased to have Lisa Lacasse, president of the American Cancer Society Cancer Action Network, or ACS CAN, as my guest. Welcome, Lisa.

Lisa Lacasse: Thanks so much, Cliff. It's really great to be with you today. I appreciate the invitation.

CH: Well, I'm really delighted that you could join me today for this discussion. And I think there are probably hundreds of topics that you and I could discuss. But I want to start with the big picture first. The American Cancer Society, of course, is a very well-known, nationwide organization with a mission of saving lives and leading the fight for a world without cancer. Can you tell our guests about the American Cancer Society Cancer Action Network, ACS CAN? What's the relationship with ACS itself? And what exactly does ACS CAN do?

LL: So thanks. That's a great question, Cliff. So many are very familiar with the American Cancer Society, which is a large, old organization that attacks cancer from every angle. The Society works to advance breakthroughs in research, treatment for patients, providing direction and information to help people manage their cancer care, and also mobilizes volunteers at the community level to really support patients in their fight against cancer. But we know that the fight to end cancer doesn't just happen in a doctor's office or a scientific lab. It really requires the government and all elected officials to join us to impact the disease. And so that effort to engage government requires advocacy. And that's where the American Cancer Society Cancer Action Network, ACS CAN, steps in. And we are the advocacy affiliate of the American Cancer Society. So ACS CAN simply urges lawmakers and rallies all of our community partners to lead in the fight against cancer. And together-- the American Cancer Society and the American Cancer Society Cancer Action Network-- although we're two independent organizations, we're working towards the same mission. However, ACS CAN uses different but complementary set of tools. So we obviously resemble ACS in a lot of important ways. We're both nonprofits. We are both absolutely, obviously evidence-based. And we're both supported by a vast army of volunteers. And we all focus on the ultimate goal of eliminating cancer as a major health problem. But ACS CAN advances this mission using tools that aren't fully available to ACS. One, an electoral program called Cancer Votes, which is really an effort to educate voters on important issues to cancer. And we also do a significant amount of lobbying. And that's not just in Washington DC, but in all 50 state capitals and many, many localities. And because of the breadth of that direct lobbying, that's often beyond what's allowable for a charity. So back in 2001, which is-- we're coming up on our 20th anniversary, which is very exciting-- the American Cancer Society Board really recognized that if we were going to achieve our goal to reduce the cancer mission, we had to do that by improving public policy. And so they decided to create ACS CAN. And my job as president is really to empower this huge network of grassroots advocates across the country. And with their staff partners-- we have about 200 people that work for ACS CAN-- every single day, they're imploring their elected officials, working with administrative officials to impact the cancer burden.

CH: Well, I mean, that's a remarkable portfolio. And I would say, obviously that ACS CAN has been a key ally and a natural partner for us here at ASCO in our own mission to conquer cancer through research, education, and the promotion of the highest quality patient care. I know that ASCO shares many advocacy priorities with your organization, including our strong support for robust federal funding for cancer research, improving patient access to clinical trials, and addressing, among other things, the alarming rise in youth tobacco use-- something listeners will recall, we discussed in detail with Scott Gottlieb last year. So it's really a privilege to be able to talk to you about all of this. One of the efforts I think that many of our listeners would want to hear more about would be the Medicare Part D, six protected classes issue. I think earlier this year, ACS CAN mounted a very public outcry and a very visible advertising campaign against a proposal that would have potentially impeded or limited access to lifesaving drugs within the Medicare Part D program, specifically in the six protected classes. And we were proud to join your campaign. We at ASCO couldn't have been more pleased than we were with the impact. Can you explain why this effort was so necessary and talk to our listeners a little bit about how it turned out?

LL: Absolutely. And I do want to say thank you to ASCO's partnership on this issue. It was really important. So this is a regulatory issue. As you mentioned, it's colloquially referenced as the "six protected classes." But that's policy that was established more than a decade ago to make sure that Medicare beneficiaries had access to innovative therapies. So really, the concept's fairly simple. If you're a health insurer and you provide a Medicare Part D plan to a Medicare beneficiary-- so you sell a Part D plan, which is a prescription drug plan-- you are, by definition, required to cover virtually all drug therapies that treat cancer, epilepsy, HIV/AIDS, mental illness, and organ transplant. And unfortunately, late last year, the Department of Health and Human Services proposed to alter that rule. And if the rule that they had put forth had been finalized, we believe it would have dramatically impacted access and affordability to critical medications for cancer patients who are part of the Medicare Part D program. So the proposal, although it was put forth as an effort to save Medicare money-- programmatically to save Medicare money-- we were really concerned that that approach would potentially have the exact opposite effect. We were worried that it would result in raising costs in other parts of the Medicare program and absolutely shifting costs to patients. So that certainly would have happened, because the proposed changes included, for example, excluding drugs from formularies or increasing the use of utilization management tools, such as step therapy. And we know that for a disease like cancer, specific drugs are very important for specific cancers. So if beneficiaries were unable to access their prescription drug that was most medically appropriate for them, they certainly would incur higher costs because it wouldn't be a covered medication. But we also were worried that they wouldn't get physician services, or they would need additional physician services because they weren't getting the right medication, and/or they would end up in the emergency room, which is all things that we know happen if you're not on the right drug regime for your cancer diagnosis. So had these proposed changes gone into effect, it really could have been devastating for cancer patients and survivors. And because of that, once we analyzed the proposed rule, we launched a multi-pronged campaign. It's one of the things that we take a lot of pride in, and we're able to address these issues in many different ways. But one of the most powerful is working in coalition. So ACS CAN and ASCO were joined by nearly 60 other patient and provider organizations. And we ran an advertising campaign-- a very visible advertising campaign. We did a Twitter Day of Action, where all of our volunteer advocates from all of our organizations directed their concern to HHS Secretary Alex Azar. We know that he heard from us. We got confirmation of that. And additionally, ACS CAN and ASCO were among more than 23 patient provider organizations actually went to the Hill for a day, did a lobby day on the hill-- again, making sure that our legislators, congressional members really understood the patient perspective of this proposed policy change. And then finally, ACS CAN did something that we actually don't do that often, which is we shot and ran some television spots. We really wanted to make sure that we were coming at this issue from many different directions because we felt it was so critical to our cancer patients and their need to have access to innovative drugs. So once we went through all of that, we were really proud and, more importantly, thrilled for our cancer patients. The final rule did not include all the proposed changes to the six protected classes that were put forth. These plans are not allowed to impose additional utilization management techniques such as prior authorization and step therapy if a cancer patient already has an established Medicaid regimen. And we really think-- we know, actually-- that HHS and the White House, hearing from doctors and patients and survivors in such an incredible coalition made the agency realize that this could be a very problematic rule. And so I want to, again, Cliff, say thank you to ASCO providing such a critical perspective from your physicians, your oncologists. They know firsthand what these barriers and delays can mean. And the partnership really, really worked. And we're proud of the outcome of that campaign.

CH: Well, again, we want to applaud ACS CAN for your bold leadership on the issue and the wonderful success. It does show the tremendous impact that we can have with a unified, collective voice on behalf of people with cancer. So another issue that I guess, in a way, relates at least tangentially to this-- and I know is near and dear to your heart-- is federal funding, in this case for cancer research and for clinical trials. But before you started ACS CAN, which I think is more than a decade ago, as I understand correctly, you were the CFO of the NIH's Cancer Research Center. So how did that experience shape your understanding of the federal research infrastructure and the need for increased funding for cancer research at the federal level?

LL: So it's a great question. And it is true. I was at NIH for nearly a decade, a decade ago. I have been at ACS CAN for just a little over 10 years now. And NIH is really a fascinating place to work. And I learned so much when I was on the NIH campus just up the road in Bethesda. And I would say most importantly and what has been most impactful is really through that time understanding that the pathways to discovery, particularly in cancer, are very long, and they're very complex, and they are extremely resource-intensive. And all parts of that journey-- every single step has to work well together from the very early scientific discoveries at the bench to ultimately bringing those discoveries to the bedside of patients. And the government has a critical role to play in that journey. Because a lot of that initial science, as you know, is risky, you really have to take a long view. And the very, very early clinical trials, which is what the clinical center focused on-- really phase 0 and phase 1, a few phase 2 trials, natural history trials-- those can only be done in certain types of facilities that have a lot of resources like the NIH Clinical Research Center. And then the other thing that I think about often as I'm doing my work is the many, many patients that I met while I was there at the Clinical Center. We had a 200-bed hospital, a huge outpatient center. And they really are the true heroes. I really think a lot about the many patients who knew that they were enrolling on trials that may or may not benefit them, but would potentially move us forward in the fight against cancer. And so I'm very passionate about the resources that are needed for NIH and NCI. And a lot of that is driven because of this, what I consider, a really transformative experience for me while I was at NIH.

CH: Well, many listeners will remember that I occasionally talk about when I was president of ASCO back in 2013 and '14. And that was the end of an era-- about a decade-long era-- where we had flat funding in dollars. And that, of course, with inflation meant a relative loss of purchasing power and missed opportunities. And this really rallied our broad community. And this is a bit of a little detour, but one of the things that ultimately helped, I think, increase the enthusiasm of many of our members for political engagement and reduce some of our cynicism is that the last few years, we've seen, instead, a steady rise and consistent support for federal funding. And it's crossed party lines. It's clearly been bipartisan. I wonder-- I mean, we like to take some credit for it-- but, of course, I was one of thousands of people knocking on doors and one of many thousands of people repeating the message. But why do you think that we currently are enjoying a period of such steady and reliable bipartisan support? And as you answer that, I would ask you to think about the future. Do you think that support can continue?

LL: Yeah. Look, I think it's a really important question. And I do think that one of the important things that we collectively lend to this discussion is a bipartisan lens. I mean, cancer does not discriminate. It is not political. We ran a big campaign, as you might remember, a few years ago that we dubbed the "One Degree Campaign," because if you are not your own cancer story, you are certainly not more than one degree away from a cancer story. I think there are a couple reasons why we've been able to rally support from a bipartisan standpoint. One is, I do think that people can clearly understand the important role government has in the fight against cancer. But also, just that our patients are very compelling storytellers. They are there, talking to their lawmakers on both sides of the aisle in Washington DC when they're in district about their experiences-- their own, personal experiences about their fight or their engagement with someone else in the fight against cancer, and how critically important federal investment is in what their experience has been. And I do think that when members hear those stories from people who've been directly impacted, or maybe they've experienced it themselves or seen it themselves, it's compelling. I think collectively, as a community, we're getting better at continuing to show the incredible impact that NIH has. And the statistics sort of bear this out, right. There has been incredible progress in diagnosing cancer, treating cancer, caring for people who have cancer. And in the last 50 years, every major medical breakthrough in cancer can be traced back to NIH and the NCI. So I think when we tell those stories, we remind so many people that people that they love are alive today because they have helped fuel that discovery. And they do that by appropriating money for NCI. And so to that end, we would like to call it an evergreen issue. Getting appropriations every year from Congress is something that we can never let up on. It is a sustained effort. And we must continue to really coordinate well among partners-- so between ACS CAN and ASCO and many, many of our cancer partners-- so that we're sure to be bringing a concerted, collective voice to this issue. And we certainly know, because we see it every day in our political lives, that Congress definitely has a habit of reacting to the latest crisis. And so we want to make sure that we don't want cancer to continue to be such a huge crisis. We want continued forward movement. And that's why it's so critical that we bring the patient voice to this issue. We are good partners, again, united with ASCO, ACS CAN, and others in One Voice Against Cancer, which we fondly call "OVAC," which is our coalition that continues to make the case on a regular basis to lawmakers and their staff. But I'm really seeing-- and, Cliff, I know you probably have through your career, as well-- but if we get the patient voice to an elected official, it's not hard for them to support our cause and to understand why these funds to NIH are so critically important to changing the face of this disease.

CH: Well, one of the ways-- I mean, one of the most tangible, obvious ways that we do that and the patients see it, of course, is through clinical trials. Those advances you describe at the NIH have to lead to clinical trials before they can actually change a standard of care. And this is another policy area where we've been working together, in particular advocating for the passage of the Clinical Trial Act. This is legislation that would federally require Medicaid to cover those routine care costs that come with participating in clinical trials, which would bring Medicaid into line with every other major payer, including Medicare, for example. Can you talk a little bit about what impact this bill would have on patients with cancer? And I ask that, reminding everybody that we will shortly post another podcast where we discuss this in detail with Melissa Dillmon, who is the current chair of our Government Relations Committee and on the front lines.

LL: And a shout-out to Dr. Dillmon, because she actually worked with us on a congressional briefing around the six protected classes. And she is a fabulous leader. So congratulations for getting her to work with you. Because her voice needs to be heard in these fights, as well. And I want to do a shout-out to ASCO for your leadership in this particular piece of legislation. So specifically with Medicaid-- I mean, Medicaid by definition obviously serves people facing financial challenges. So right now, it is, as you mentioned, the only major category of insurance where routine costs in cancer clinical trials aren't covered. And so just to be clear, there's the experimental part of a cancer trial, but there are also maybe just regular standard of care that a patient would be getting even if they weren't enrolled in the trial. And those are the costs that you're talking about in this piece of legislation, and that when we talk about the financial challenges of enrolling on a clinical trial, it's not the experimental part of the trial itself. It's really the care around that. So currently, only 12 states and the District of Columbia have state requirements that Medicaid cover these routine trial costs. So that means 38 other states, if a patient wants to enroll in a trial, they're responsible for 100% of that routine costs out of pocket, which we know very few Americans could afford, much less those on a limited incomes. So to us, we see this as essentially a ban on participation by Medicaid patients, which really doesn't make any sense since, by definition, those routine costs would certainly be covered if they were seeing a doctor just on a regular visit. And we also don't want to exclude this whole cohort of millions of patients that we want to have participate in these clinical trials, since that is a critical success factor, as you noted, getting discovery out there that can impact a cancer diagnosis.

CH: Well, while we're on the topic of Medicaid-- and here we were focusing on coverage of its beneficiaries' participation in clinical research-- but can you talk a little bit about your Medicaid Covers Us campaign? How does that relate to this, if it does at all? Or what direction does that take us in?

LL: So Medicaid Covers Us-- I really hope that people that are listening to the podcast can take a minute and go to our URL, which is medicaidcoversus.org. And this is a campaign that we launched last year. And although ACS CAN has a very long history of advocating for Medicaid, Medicaid is just an insurance coverage, right. It just happens to cover a lower level of income for patients. But really, the focus of that program is to improve access to screening, diagnosis, treatment, which happens if you have insurance coverage. So when the Affordable Care Act was passed, there was an opportunity to expand Medicaid, although it is optional for a state. ACS CAN has worked hard with many partners to actively advocate for expanding and really educating the public on how important Medicaid is in the insurance landscape. And so part of that-- what we realized is that we really wanted to make sure that people understood what Medicaid truly is. And one of the ways we are doing that is through this campaign. And this is a public education campaign that's really trying to create a dialogue for everyone who touches health care, which is really an entire community, to understand the importance. If you want to achieve a healthy community, healthy economy, health care is a really important part of that. And Medicaid plays an important role in health care. So we decided to pursue kind of this larger educational effort, and it's really been an exciting project. We have gotten a lot of opportunity to have many members of a community have this conversation. And we're excited about the role that we're able to play in continuing to make sure that people understand that quality cancer care needs access to insurance. And access to insurance for many, many people means access to Medicaid.

CH: So really, in the last few moments we've talked about Medicaid from two perspectives. One is coverage for a substantial bloc of Americans at about 42 million, if memory serves me correctly. And the second is specific coverage of a vulnerable subset that is those beneficiaries who need access to clinical research for advanced cancer or cancer at all. Is that a fair summary of the two prongs of this effort?

LL: 100%, 100%. And I think that we want comprehensive coverage. And Medicaid provides, again, a lifeline for so many patients. And we really want to work to address a couple of big challenges right now in Medicaid. One is that there still 15 states that have not fully expanded their Medicaid program. So that means that there are low-income parents, adults that are not able to access affordable health insurance. And we've seen through a significant amount of research that we've done on our end that there are a lot of cancer patients in the Medicaid program. So that program itself is very, very important to our mission. And then another issue that we're paying a lot of attention to and trying to make sure through ACS CAN that we're having influence on, our policy changes that are creating some barriers if you actually are in Medicaid-- things like what are known as 1115 waivers that are introducing things like work requirements, or maybe some other types of barriers like a lockout period that really create a significant barrier in a pathway for patients to make sure they continue to be able to seek care. So we want to make sure that for all Medicaid enrollees with serious conditions like cancer, that they're able, one, to continue to work-- if they are unable to work, though, that they don't lose their coverage. So we are continuing to work on many, many components of Medicaid, so both the public education and awareness, but also a lot of these very direct lobbying issues.

CH: You know what's interesting, I was thinking as you described all that, the ability to understand the system and then help to constructively shape it is, in fact, the reason-- personally, I can tell you-- that I was so interested in making the career change to go from breast cancer doctor to ASCO CEO. You've been at ACS CAN in total, as we heard already, for just about a dozen years. But recently you stepped into the role of president for the organization. So thinking about all of this, I wonder, has your view of the organization and its role and potential changed over these years? And what are the things that you want to focus on, going forward with this tool that you now have at your disposal?

LL: Yeah. So that's a great question. I'm almost at my six-month mark, so that's very exciting. And it's certainly interesting and always very, very different to work in an organization from a different vantage point. But as president, the first thing I'll say as I continue to be unbelievably impressed with our partnerships and our staff and our incredible volunteers nationwide and their ability to impact policy through very deliberate approaches that we have trained people on-- and when we're clear about the impact that we can have and we talk to our legislators about that impact, we've found a lot of champions. I continue to be very proud, but also convinced that the role of advocacy is critically important to the future of cancer and changing that future for more and more people to have more opportunities to successfully fight their diagnosis. And for organizational goals, I think we obviously want to continue to grow ACS CAN. The bigger our organization is, both from a network of volunteers to resources, the more influence I know that we can have. And then finally, a personal passion of mine is to make sure that our organization is relevant to the entire cancer ecosystem, but particularly everyone who is going to face a cancer burden. And we know that cancer burden is unequal in many, many segments of our population. So I feel a great responsibility and drive to work with my many colleagues, including you, Cliff, and ASCO, to do everything we can to very deliberately reduce the disparity of cancer.

CH: Well, that's an inspiring way, I think, to wrap up this conversation. I can't thank you enough for joining me today for this ASCO in Action Podcast. ASCO and ACS CAN share so many common goals, as I'm sure everybody will hear through this conversation. And we are both dedicated to helping people whose lives have been affected by cancer. And when patients, survivors, families, cancer care providers work together the way we do, and so many others, it's clear that the results can be tremendous in terms of impact and change. So thanks again for leading this charge with us.

LL: Well, Cliff, it really was my pleasure to do this today with you. And I look forward to many years of productive partnership between ASCO and ACS CAN. Thanks for having me today.

CH: Sure. And for all of you listening, if you want to keep up with ASCO's advocacy efforts, I encourage you to visit our website. This is ascoaction, written as one word, .asco.org. And there's more information about ACS CAN and Medicaid Covers Us available at fightcancer-- that's written as one word-- .org. And, Lisa, I think you previously told us that there's a special website for Medicaid Covers Us. What's that URL again?

LL: Medicaidcoversus.org.

CH: I don't know how I forgot it. So until next time, thank you for listening to this ASCO in Action Podcast. If you enjoyed what you heard here today, don't forget to give us a rating or review on Apple Podcasts or wherever you listen. And while you're there, be sure to subscribe so you never miss an upcoming episode. The ASCO in Action Podcast is just one of ASCO's many podcasts. And you can find all of them at podcast.asco.org.

Aug 06 2019
31 mins
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Policy Program Helps Oncologists Advocate for Their Patients, Fellows Say

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Dr. Joanna Yang and Dr. Robert Daly join ASCO CEO Dr. Clifford A. Hudis to discuss the Health Policy Leadership Development Program (HP-LDP). As former fellows, Drs. Yang and Daly provide insight as to how the program has made them better advocates for their patients.

TRANSCRIPT

Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

Clifford Hudis: Welcome to this ASCO in Action podcast. This is ASCO's monthly podcast series, where we explore policy and practice issues that impact oncologists, the entire cancer care delivery team, and the individuals we care for, people with cancer. My name is Clifford Hudis. And I'm the CEO of ASCO as well as the host of the ASCO in Action podcast series. For today's podcast, I am delighted to be joined by not one, but two of ASCO's rising leaders, Dr. Robert Daly and Dr. Joanna Yang. Both Dr. Daly and Dr. Yang are recent participants in ASCO's Health Policy Leadership Development Program, formerly known as the Health Policy Fellowship Program. This is a professional development program designed to build health policy and advocacy leadership expertise among our members. It's a one-year program where fellows get practical experience working with our policy and advocacy staff and council to craft policy positions and statements, along with other educational sessions on communication, leadership, and advocacy. Starting this year, participants will be able to participate as well in ASCO's Leadership Development Program, which offers mid-career oncologists the opportunity to improve their leadership skills and gain valuable training to set them up to be future leaders in oncology. Dr. Daly and Dr. Yang, welcome, and thank you for joining me today.

Joanna Yang: Thank you so much for the opportunity.

Robert Daly: Yes, thank you so much for having us.

CH: So Dr. Yang, I'm going to start with you. You were an ASCO Health Policy Fellow in 2017-2018. And I want to kick off our discussion by talking about what brought you to the program. Why were you interested in developing special expertise in policy work?

JY: Sure. So I've always been interested in health policy. And I had the opportunity to study health policy and health economics during undergrad. But of course, studying health policy is very different than creating or influencing health policy. When I started residency, I saw many ways in which health policy on a national level or even state level affected the patients I was caring for. And I felt compelled to do more. But the issue is that there is never any clear way for me to get involved or even to learn how I could learn how to shape health policy. And that's why the ASCO program is so great. I feel like it came at exactly the right time. I was looking for a way to learn more to develop the skills I needed to influence health policy. And ASCO came out with this structured and immersive experience where I could take the things that I had studied in school, and also the things that I'd seen in practice, and use them to actually have an impact on the patients I take care of.

CH: So Dr. Daly, you as well were one of our inaugural Fellows. What prompted your interest in applying for the program, especially given I think you were the first year?

RD: Yes.

CH: Right, so you took a leap off of the ledge there and said, I'll go first.

RD: Yeah, I'm similar to Dr. Yang. I had a real interest in cancer care delivery research during my fellowship at the University of Chicago. And I was lucky enough to be mentored by Funmi Olopade and Dr. Blase Polite. And Dr. Polite was really fundamental and helped developing the ASCO Health Policy Fellowship. And so I really saw this as an opportunity to augment that training but really gain skills in leadership, advocacy, and health policy, areas that I hadn't had exposure to in the past. So this seemed like the perfect program for me at that point in my career.

CH: I have to say parenthetically that I'm jealous of both of you, because while I was personally drawn, especially in later years in my career to the policy and advocacy aspects of work with ASCO-- and it truly is the reason that I moved from my traditional academic career to this role as CEO at ASCO-- I never, of course, had the opportunity to be trained and to learn how to do this professionally as you two have. So I am in awe of your accomplishments, as well as the opportunities that are going to continue to unfold in front of you because of this. So given that, and given that this is really the beginning, we hope, of a career with impact, we should talk a little bit about what you actually did. The program, as I mentioned earlier, lasts for a year. And during that time, Fellows worked very closely with our policy staff on a mentor project. So I'll start again with Dr. Yang. Can you talk about the project you worked, what it entailed, what you learned, and where this is going?

JY: Sure. So I worked on a two-part project with Alex Chen, who was my co-fellow during the past year. And as you hinted at, the work is actually still ongoing. So the first part was we looked at whether a bundled payment model could work in oncology. And this really culminated in a white paper for us. But the second part of the project, which built on the first part, was really the most fascinating. In the second part, it was really asking, if not bundled payments, then what? And we actually built on some of the work that Dr. Daly did that he'll probably describe in a little bit. But we actually worked on designing a pathway-based alternative payment model. And of course, going into this, I had no experience designing alternative payment models at all. But the beauty of the program is that from the very beginning, Deb Kamin, said, we will not be having you do any work that is not necessary. So all the work that you do is important to ASCO, is important to our patients. And that was really true for our project. So we were able to work with the ASCO staff, and our mentors, Ray Page, and Linda Bosserman, and a whole team of experts to create an alternative payment model that we thought would allow oncologists to prescribe the right drug at the right time, without being penalized by the high drug costs.

CH: So I guess, based on that, we really should have started with you, Dr. Daly. But your mentor project was centered around clinical pathways. And I understand that ends up being the foundation for the alternative payment model that Dr. Yang just described. So can you talk a little bit about that process, what you did as an inaugural fellow in this and what you learned as you went through the work? RD: Absolutely. So I was lucky enough to be able to serve on the ASCO Task Force on Pathways. So that was an incredible experience for me because I really got to interact with leaders on this issue, including Robin Zon and Ray Page, who are very active in cancer care policy, both at the state level in Indiana and Texas, but also on a national level. So to be able to gain their mentorship that early on in the fellowship was really a great asset for me. And we were looking at, how do we write the criteria for what constitutes a high-quality pathway? So I really got to see, from soup to nuts, how do you write a policy statement? How do you solicit input from those important stakeholders? So the stakeholders in this case were fundamentally the patients, but also providers, ASCO's Government Relations Committee and State Affiliate Counsel, ASCO's board, the vendors-- get all of their input together to create a policy statement that can really influence change. And then lastly, I played the part of representing ASCO and in discussions with the pathway vendors about these criteria for high-quality pathways. So I learned about the important role ASCO can have on influencing the development of products and services that impact patient care, but also the impact ASCO can have on legislation. So in California, Connecticut, and other states, they started to look at policy around pathways, policies around implementing the criteria that ASCO had developed, so that those pathways that were being used in their state were high quality. So it really showed me the reach of ASCO and the impact of ASCO on patients and providers. CH: That is amazing because it really is a reminder-- and I'm going to come back to this idea-- about how much impact one person and one project can ultimately have. And I think that in these sometimes cynical times, people forget that. I alluded to this before about my own engagement with ASCO was accelerated by my experience as an advocate on Capitol Hill-- again, an amateur to your professionalism. So I wonder if you would reflect on your experience during the fellowship program. I understand you were both frequently called on to join in advocacy meetings on Capitol Hill. And this is with federal agencies, as well as, I assume, with representatives, senators, and their staff. Did either of you have any experience doing this before ASCO took it to Capitol Hill? RD: I had never had any experience doing advocacy meetings. So it was really-- the fellowship really helped me learn how to do that and how to do that effectively. CH: What was the first meeting like? RD: My first meeting was here in Manhattan. It was at the office of Senator Gillibrand. And I was accompanied by Heather Hilton, who is an ASCO advocate and someone who's served on the Government Relations Committee. And I was really nervous. I didn't know what to expect. But we met with one of her health policy staffers and really had an engaging discussion about an ASCO advocacy issue where we really felt heard. We were able to share patients' stories and also deliver data that ASCO had collected to help support our view. So it was really an exciting experience for me. And then I got to replicate that experience on Capitol Hill, meeting with congressional representatives from New York in their offices, but then also, as you said, going to government agencies, which was a different experience as well. So I really got to see a broad perspective of how you can advocate for policy issues for ASCO. CH: Dr. Yang, how would you describe your initial advocacy meetings for someone who hasn't participated before? What does it feel like to walk into that first meeting and begin that first discussion? JY: Sure. I've done that for my friends before. I've described these meetings. And they always say, it's really not at all what they expected. And I think that Dr. Daly's description is exactly right. So you go with your group-- usually it's by state-- to the member's office. And then depending on how much room there is and how many meetings are being held that day, your meeting is either going to be in a conference room in the member's office or even, more frequently, in the hall or any room that's available. And the member is not always there, but one of their staffers is, or sometimes multiple staffers, who are always really young but super, super, super knowledgeable about the issue. Basically, you go around, and you introduce yourselves and then describe the issues that you're here to discuss. And it's interesting because ASCO always does a great job of making you exceedingly well-prepared with the facts. But the truth is that most members and most staffers are most interested in hearing the patients' stories, which is why it's so important that oncologists come to the Hill to have these meetings. I think that no matter how well you try to prepare, ultimately, it really just comes down to engaging with the staffer and finding some area of common ground. And cancer is so common that most of the time in these meetings, I find that staffers or members will say, I have a family member or friend or some other loved one who has cancer. And it's really great that you guys are here. CH: My own experience-- I mean, I'm here to talk to you. And the listeners want to hear from you. But I just can't help but share. When I got involved in this before you all were, the key issue that we were confronting was the decade-long flat-- in dollars-- flat funding of the NIH and the NCI. And my first trips to Capitol Hill consisted of virtually beating on doors and explaining why this was a mistake for the country and for our people, and getting what felt like the cold shoulder. Over and over again, the same arguments seemed to fall on deaf ears. But-- and this is an important "but"-- what I have learned is that repeatedly making rational, evidence-based, and appealing anecdotal arguments, just as you describe, can ultimately move the needle. And it does. And so my personal cynicism with regard to politics and making a difference has gone down, not up, with aging. And I think listeners should think about this. You will never go to a congressional office and change a mind in one quick phone call. But when dozens and hundreds of people do it repeatedly over months and years, we actually do have the chance to positively influence policy and legislative actions and regulations in the United States. And you should forgive me for waxing so poetic. You should be proud that you've committed to doing this early. And I hope you start to see the rewards. So I'm sorry to carry on about my own experience here. But it really is part of what has helped motivate all the staff to get behind this program and launch it and support it. Looking back, I'll turn back to you Dr. Daly. You're a couple of years removed now from the program. Can you identify one or several key learnings from your time as an ASCO Policy Fellow that have stuck with you, that you find yourself coming back to in your daily life? RD: Yeah, I mean, I think what you've just said, Dr. Hudis, about how you can really have an impact is something that I learned during this fellowship. It wasn't something that I had been aware of in the past, because I had never done advocacy work before in the past. So I think what this fellowship really trained me to do is to be an effective advocate. And that is something that I can use in a multitude of different areas as an oncologist. So combining the patient stories that we talked about that are so visceral and so needed when you're trying to get through to those legislators or policymakers that you're trying to reach-- but also backing that up with data, and I think ASCO really equipped us well as advocates to have the data, as well as the personal stories, to influence change. So using tools like CancerLinQ to be able to look at broader data sets and say, we know this is impacting our patients. We can see that. And now we need to think of a solution for change. And I think being involved in helping to create some of those solutions was also really valuable for me. So with the pathways, creating the policy paper, but also serving on committees during that fellowship year on MACRA and other issues, like opioid legislation, that were really affecting our patients, and seeing how ASCO is effecting change in those areas, was something that will stay with me throughout my career. CH: And how about you, Dr. Yang? Do you see any practical day-to-day impact, for example, in your work with patients from your time in the fellowship? JY: Yeah, absolutely. I think because I spent most of the past year thinking about high drug costs, both for chemotherapies, immunotherapies, and supportive drugs, I'm much more thoughtful about the costs that are passed on to our patients. And that can actually be really significant. And one of the things that I do much more often is I ask about cost to my patients when I prescribe medications. And that I really attribute directly to work that I was doing with ASCO. The other thing is that working with patients actually often gives me ideas. So I'll see patterns emerging. And I'll think, we really need to work on a policy that addresses this. And the great thing about the Health Policy Fellowship is that you remain involved with ASCO. So when I see these issues, I'm able to take them back to ASCO and to the committees. CH: Well, speaking of the committees, after you and all of our Fellows complete the one-year program, you were automatically added to one of ASCO's relevant committees. And I think you're both members of the Clinical Practice Committee. I'm curious-- I'll start with you, Dr. Daly-- has your time as a Health Policy Fellow helped you in your work on the CPC, and how? RD: I think, absolutely. It's made me more fluent in the issues that the CPC is confronting, the sort of things like the Oncology Care Model, rural cancer care. I now have a foundation where I'm able to contribute in a way on that committee that I never could have before or without the Health Policy Fellowship. CH: Yeah, I think it's often the case that sometimes-- or I shouldn't say often-- I think sometimes it's the case that people get onto committees and really do have a steep learning curve. It seems like maybe this could have accelerated your start on the committee. Is that your experience, Dr. Yang? JY: Yeah, I think so. I think that the Health Policy Fellowship, that first year is a really steep learning curve. But it does, as Dr. Daly said, provide a great foundation to just be aware of all of the issues that affect cancer doctors and cancer patients. CH: So I'm going to go to a little bit of a speed round, if you will, and ask you both to think about the other members of our community who have not had the opportunity to do this and might not ever have thought about it. Dr. Yang, finishing the program last summer of course-- so it's fresher, I think, for you-- why do you think it would be important for oncologists to be aware of and engaged in policy discussions, rather than nose to the grindstone, thinking about their clinical and research responsibilities on a daily basis?

JY: Mainly, I really think that the reason for oncologists to be involved in this is that regardless if you are thinking about it or not, health policy affects you. And it affects oncologists. It affects how they practice. It affects how they are able to care for their patients and the type of care that they're able to provide. And if oncologists aren't involved, their voice is going to be lost. And oftentimes, they're the most important voice for their patients. CH: And Bobby, what would you say to the old version of me, the cynic, who says, this is a waste of time-- I'm not getting involved?

RD: Well, I do think it really makes your career more exciting to be involved in health policy issues. It really broadens your view of how you think about patients and how you think about cancer care, and makes coming to work every day, I think, more exciting because you have this other lens that you're looking at issues with. CH: And looking back more specifically, and not intending to turn this into a sales job for the Policy Fellowship-- we only have two slots a year-- but I wonder what each of you would say to young colleagues thinking about this. What's the best reason to get involved in the Health Policy Fellowship at ASCO? I'll start with you, Dr. Yang. JY: I think that if you're interested in quality of care, the costs of care, access to care, then this fellowship is the right fellowship for you. And I think that being interested in those things doesn't necessarily provide you with the skill set you need to actually do meaningful work in that realm. And I think that the fellowship program really does provide you with tangible skills that you can then use to write policy briefs, to hold meetings, to be an advocate, all of which are really, really, really important. CH: Dr. Daly, is there anything you can add to that? Or does that pretty much sum it up? RD: I think that's absolutely right. I would just add the mentorship of the fellowship is really incredible, so getting to interact with the ASCO leaders, like Robin Zon, or Ray Page, or Blase Polite, but also the ASCO staff as well, who are incredible in the policy area, like Deb Kamin. I think I learned so much from being in their presence for a year and just absorbing all of their knowledge that they had, an experience they had. And when I was at the annual meeting just a couple of weeks ago, it was just such a fun pleasure to be there and see all of them and know that those relationships are something that will be with me throughout my career. And they really influenced me. CH: Wow. I think that's great. And I am so proud of both of you and all the participants in these and the other development programs that we offer. I will share with you that from the perspective of the board of directors, these programs really represent the crown jewel, something that the board members take the light in. And you should be proud to have contributed the way you have. So Dr. Daly, Dr. Yang, I want to thank you again for joining me today for this ASCO in Action podcast.

RD: Thank you so much for having us.

JY: Thank you.

And for all of our listeners, if you want to learn more about ASCO's Health Policy Leadership Development Program, please visit us at asco.org and search for "policy leadership." The application period for the 2020-2021 year is now open, and it will be open through the end of September. So there is time to get those applications in. And with that, until next time, I want to thank everyone for listening to this ASCO in Action podcast.

Jul 09 2019
22 mins
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Director of the FDA’s Oncology Center of Excellence Discusses Expanded Access, Accelerated Drug Approvals

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Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care, and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

Dr. Clifford A. Hudis (CH): Welcome to this ASCO in Action podcast. This is ASCO's monthly podcast, series where we explore policy and practice issues that can impact oncologists, the entire cancer care delivery team, and the individuals we care for, people with cancer.  My name is Clifford Hudis, and I'm the CEO of ASCO, as well as the host of the ASCO in Action podcast series. For today's podcast, I am delighted to have as my guest, Dr. Richard Pazdur, the Director of the Food and Drug Administration's Oncology Center of Excellence.

The OCE was established to expedite the review of novel cancer therapies and products by bringing together expertise from across the FDA. And we'll touch on this a little bit during our conversation. Dr. Pazdur, welcome and thank you for joining me today.

Dr. Richard Pazdur (RP): It's a pleasure Dr. Hudis.

CH: Thanks. So I want to kick off our discussion by diving right into a hot button issue, expanded access. Can you provide our listeners with some background on this, and explain what the FDA's expanded access program is, and why an oncologist might want to pursue expanded access for an individual patient?

RP: Of course. The FDA's expanded access program provides a way that patients with serious or life-threatening diseases or conditions such as cancer can try investigational medical products for treatment when no satisfactory therapies are available, and when there is no opportunity for the patient to enroll in a clinical trial. The process-- to make a request, the patient's physicians will approach the pharmaceutical company to ask for its agreement that the company will provide the medical product.

The company has the right to approve or disapprove the physician's request. Then the physician needs to send the request to the FDA. This process can be complex to navigate, particularly for oncologists or physicians who don't have experience working with the clinical trials or these types of requests.

FDA allows the vast majority of these requests to proceed. And the FDA has been working to improve the expanded access programs for a number of years, including the development of a more streamlined application process, a more streamlined form. But for many key health care professionals, especially those not familiar with the expanded access program, this process may appear confusing or somewhat burdensome.

CH: And so is this a segue to Project Facilitate, which you announced at our annual meeting a few weeks ago? Can you talk a little bit about that and, its practical implications?

RP: Yes. The Project Facilitate call center is a pilot program only for oncology that will serve a single point of contact. We have FDA oncology staff there, oncology nurses, oncology pharmacists who will assist the physician and their health care team throughout the process to submit and expanded access request for an individual cancer patient.

This is a concierge service to support the patient's medical team throughout the process. It ranges from the initiation of the FDA form 3926. The process will also provide information about IRBs, particularly central IRBs, and really will also follow up on the status of a given patient to determine if that patient has received any benefit from the therapy and if there were any adverse events that need to be reported to the FDA.

CH: So imagine that Project Facilitate works as hoped for. What's the thumbnail before and after experience? That is, how will things appear to be different to the physicians and to the patients?

RP: It should make the process easier for physicians to get information that they need to submit an expanded access request. As I said before, it's often somewhat complicated, especially for physicians don't have experience with either the drug or with the process. And it's obviously easier to talk to somebody over the phone to ask specific questions rather than just being directed to a website.

We're also working in conjunction with Reagan-Udall Foundation for the FDA, which started the expanded access navigator website to educate patients and health care professionals about the expanded access process. This navigator approach offers information provided by companies about their expanded access policy, and now includes the expanded access programs listed in ClinicalTrials.gov.

Patients and physicians can look for treatment options. They could discuss clinical trials, and company information could be provided at the navigator at Navigator.Reagan-Udall.org. So this is really to give patients and their physicians information about what is out there.

Once the patient obviously has this information and their doctor, then the doctor can utilize the Project Facilitate, which allows easier access to actually submitting these forms and going through the actual process. I'd like to emphasize that companies are now required by the 21st Century Cures Act to publicly list their expanded access policy. And the Reagan-Udall Navigator website helps them comply with that requirement.

Again, so once the physician and the patient have identified the investigational therapy they want to try, the physician or other members of the health care team then can contact Project Facillitate for assistance in locating IRB resources and help with the FDA form 3926.

CH: So I think you mentioned this when you launched this or announced it at the annual meeting just now, that physicians do already-- or at least before project facilitate often would successfully go straight to pharmaceutical companies and ask for treatments. And I guess in some cases they'd be denied, and in some cases they would be approved. And that would be through the company's expanded access programs.

Obviously, that means that regulators wouldn't necessarily know the full extent of expanded access use. So assuming that Project Facilitate will allow the FDA to collect much more data on expanded use, how will the data be useful? And obviously, I'm hinting at the fact that some fear that it will be actually a negative.

RP: Well, prior to launching Project Facilitate, the expanded access requests for cancer patients arrived at multiple places within the FDA and were forwarded separately to FDA oncology or hematology

divisions. Sometimes these requests could be delayed, being sent from one place to another in the agency. So this gives a focus point for physicians to contact.

In addition, we're seeing that most of the expanded access requests were coming from patients and physicians at larger academic centers. The patients who don't live near these cancer centers and may not be able to get on clinical trials can also hopefully have access to investigational agents by having a more facile and easier process to use here.

We're also seeing that many companies have turned down requests from patients, and we have no idea what really the number of requests a company may get if they're turning down these requests. Because generally, they don't come to the FDA. So really, by having the initial contact at the FDA we'll be able to determine number one, the number of patients that are requesting a single patient access.

We'll also be able to determine and discuss with the companies their reasons for denying these requests. And there could be multiple reasons. And we also have a process in place that can follow up with what are the benefits that an individual patient may have from this therapy or, as I stated before, were there any adverse events.

We have also heard this kind of urban myth-- and I label that in quotations, "urban myth," that companies fear that perhaps adverse events may be held against them when their drug is coming for drug approval. We have not done that. We take into context where the adverse event reporting is coming from. And there really are no instances that I am aware of in oncology where a report of an adverse event has delayed or curtailed an approval of a drug.

CH: So really, this is a bright ray of sunshine on a dark corner of drug access. And if it works right, you'll just have much more understanding of the overall use of expanded access. Right?

RP: Yeah. I think that gives some clarity to the process here. Here again, we don't know the numbers at this time of actually the number of patients. We only know the numbers of patients that receive a affirmative position from the drug company regarding that the process can continue.

But we don't know the numbers of patients that may be requesting single patient access and are denied by an individual drug company. And also, the reasons. And, as I stated before, there can be very legitimate reasons, including inadequate supply of the drug, lack of support staff to follow up on these drug requests, potential interference with clinical trials that the patient may be eligible for.

CH: You just used a phrase about patients requesting. And I thought as you described this process you were referring to physicians requesting on behalf of patients. And so I do want to ask, are there resources that are aimed directly at patients or is it really solely aimed at the oncologists in this case?

RP: Well, here again, this is a two-prong process. Project Facilitate, the FDA portion of this, is for physicians to call up for assistance in filling out the form and also navigating the process once the decision is made. The other prong of this is, as I stated before, by Reagan-Udall foundation, which patients can call to look at what our options available to them that are potentially listed on ClinicalTrials.gov. And that is also for patients and physicians. However, the portion of the program that is Project Facilitate is for the requesting physician.

CH: All right. Well, that's clear. So once we talk about patient's involvement, and even many physicians I think for that matter, we quickly can drift towards the very heated discussion that took place in public over the last year in the area or that we call Right to Try. And I wonder if you could talk for a minute and help us, for the listeners, make this distinction between expanded access and Right to Try.

RP: Of course. These programs, Right to Try and single patient INDs are really mutually exclusive programs. The main difference between these programs are first, that under Right to Try the drugs have to complete a Phase I trial. For single patient INDs, it could be done anywhere, even within the context that the drug is being conducted in a Phase I trial.

However, the major difference is that the FDA and the IRB does not review Right to Try applications, whereas under a single patient IND, the FDA obviously has to give permission for the patient to proceed as well as an IRB has to review these requests.

CH: So to be very clear, Project Facilitate is supporting the single patient INDs, and Right to Try is a separate matter entirely.

They are distinctly different programs. Project Facilitate does not apply to Right to Try. That is an independent, separate program.

CH: Great. So, you know, one of the problems for a busy clinician is figuring out how to do all this under pressure with a sick patient, and the other pressures of clinic and administration and research. If our listeners want to learn about this more casually, where can they go not under duress, just to start reading up and learning about how to access the program?

RP: They could go-- physicians can go and learn more about the program at our website, www.FDA.gov/oce. The Project Facilitate phone number is 240-402-0004. That's 240-402-0004. And the email address is ONCProjectFacilitate@FDA.HHS.gov.

CH: That's great. So hopefully, some of our listeners will take advantage of that and learn about this when they're not under pressure so that they're familiar with it if they have to turn to it some months later. Now you mentioned that the host is the Oncology Center of Excellence. And I mentioned in my introduction that we would want to talk a little bit about that.

CH: You've been at the helm of the OCE since it was established a little over two years ago, I think. Now that you've been in the role a while, I wonder if you could talk a little bit about your view of what the OCE should be accomplishing, and maybe how that aim has evolved over these two years.

RP: Yes. The OCE basically was an offshoot of the Moonshot Program several years ago, and was aimed to be the first center that coordinates activity among the therapeutic center. Obviously, at the FDA there is a center for drugs, a center for biologics, and a center for radiologic health and devices.

And they all can review oncology products. The OCE has a designation to really coordinate the activities, particularly in the clinical review of the products that involve the treatment of cancer. So, this is a unique center within the FDA, and is somewhat of an experiment at the FDA to see how we can really coordinate the activities of drugs that affect cancer patients.

And here again, the oncology center is primarily designated for the clinical review. And we don't really get into the manufacturing of drugs. That's handled in the individual centers, whether it be a biologic and CBER, the Center for Biological Evaluation and Research or CDER, the Center for Drug Evaluation and Research.

With that given said, in addition to the actual bread and butter of reviewing applications, we have many research projects that we're doing. We have a big project looking at real world data. We have a project looking at updating labels called Project Renewal.

We have, as I stated before, this project that we launched at this year's ASCO, Project Facilitate. We also have a project aimed at really improving our relationships with international drug regulators. We have monthly meetings, teleconferences with five different regulatory agencies throughout the world to go over applications and discuss different regulatory policies.

We have a host of a symposium that we conduct both here at the FDA, inviting external stakeholders including physicians, leading academics, patients to come to the FDA really to discuss important topics to our drug reviewers and the entire discipline of regulatory and oncology, so to speak, how we make decisions in medicine.

We have a whole, also, program that we're developing aimed at educating physicians and other health care professionals for educating other health care professionals on how we evaluate drugs, what our thought processes are here at the FDA. So, in addition to the regulatory work, there is a whole body of scientific work that we're also doing, including independent research on different databases, looking at patient populations more likely to respond to different drugs, ways of evaluating and describing toxicities, ways of really looking at patient experiences while they're getting drugs, and different ways of reporting patient reported outcomes.

We'd like to thank ASCO, obviously, for their assistance during and helping us with many of these projects throughout the year, especially the educational projects involving fellows, involving different topics that we've found of interest that needed to really have a public disclosure in the community, really, to get input from leading academics, as well as treating physicians.

CH: Wow. You are busy. And there's a lot we could unpack there. But I do want to pick up on a couple of things. First of all, you described this as an experiment, so I'm curious. And not to put you on the spot, but if you have an experiment, I presume that just some metric that you would use to call it a success or failure. And I wonder where you think you are right now in that regard.

It sounds like you've gotten a tremendous amount done. But are you satisfied, for example? Have you covered the ground you wanted to or do you think that you could be doing more?

RP: Well, people who know me realize that I'm never satisfied. So, I think we're in the middle of this experiment. I think it's going quite well. And I think that this is really going to be aimed at-- and the evaluation of the success or failure of this is going to be really how the individuals that work here at the FDA really evaluate drugs and how we facilitate the evaluation of drugs.

And also the really important of retention of staff here at the FDA is a major issue, also. And I think many of the projects that we have ongoing really develop our reviewers in really having a real world approach to how oncology drugs are used. So it's very difficult to say what success and failure will ultimately be. But I think we're on, really, the correct path, and pretty much a straight path of looking at a successful venture here.

CH: You know, one of the things you said reminded me of another urban myth. And I don't know if you realize this. But when you describe the careful coordination with, I think you said five regulatory agencies around the world, it raises the myth, I believe, but you can address this with some facts, that many people in the United States believe that others around the world have faster access to a broader range of effective therapies. I wonder if you want to expand on that or comment on that at all before we move on.

RP: Well, that is an urban myth, and probably was generated 20, 30, 40 years ago when that may have been the fact. Obviously, that antedated my coming to the FDA. But I can say the vast majority of drugs are approved first in the United States.

And those include very important drugs such as the PD1 drugs, the targeted drugs, et cetera. They are approved first in the United States. We have taken a very active approach to really rapid approvals of our drugs without sacrificing quality, by having a smarter approach to how we review these drugs, with putting multiple reviewers on particular applications, by cutting down on unnecessary paperwork that many of our reviewers had to do, and really focusing on really the core material that we have at hand, and really emphasizing does this drug really demonstrate safety and efficacy.

At the end of the day, I charge all of our reviewers with the following statement. Would the American public be better with this drug than without it? And that's the ultimate decision that we have to make at the time of approval.

CH: Well, that's another perfect segue to a hot topic, which you and I have discussed actually offline before this. But I'm going to come back to it. The expedited approval of anticancer therapies was recently the subject of a paper in The Journal of the American Medical Association.

And if I remember correctly, they looked at 93 cancer drugs that had been approved through accelerated approval process. But what they claimed is that only 19 of the 93 clearly extended the lives of the patients taking them. That's a value judgment, obviously, about why drugs are approved and introduced to the market. But I wonder if you would want to talk a little bit about your view of some of the complexities and challenges that are inherent in accelerated drug approval, and what your view is of this particular study of the approval outcomes.

RP: I think many times people don't understand that it isn't just about overall survival. Obviously, that's the gold standard. But we've had very careful discussions throughout the years that there are many ways to evaluate benefit to the patient.

And that includes reduction of the size of the tumor, delay in the progression of the disease, the establishment of complete response rates in hematological diseases. So we have to have some flexibility, both in terms of how we approve drugs and what clinical trials we're going to ask for after drugs have been approved on the accelerated approval pathway.

Although overall survival is a very important end point, it's an important efficacy endpoint as well as a safety endpoint, it does have limitations. As we move more toward a targeted therapy and subsegment common diseases into molecular subtypes, many times we find that we have very limited populations.

And simply, we don't have the size of a population that we approve the drug on to really do a large, randomized trial.

So we have to weigh that issue with what type of trial we're going to ask for, both with the initial approval of the drug as well as with, perhaps, the subsequent studies that we ask for after an accelerated approval. In addition to that, many times we find that we have situations where the disease itself may have a very long natural history, such as CLL or other diseases that may have very long natural histories, where one cannot really do a long-term survival study because it would extend many, many, many years.

And many times-- and I think we have to be realistic about this, that there may not be equipoise here to allow a randomized trial to be done looking at overall survival as a primary end point. For example, if we already have information that a drug may have a response rate of 50% or 60% and the comparator drug may have a response rate of 10%, patients will not want to go on a study that looks at overall survival as the primary end point.

And many times, we have to take a look at time to progression or progression free survival and those end points, and actually allow for a switch in therapies or crossover at the time of disease progression, which renders the evaluation of overall survival somewhat difficult, and may confound that evaluation.

So, there are many reasons why overall survival, although a gold standard, may not be applicable to all situations. And I think that's going to be increasingly so as we get into a more targeted therapy approach and have better definitions of who is going to respond. So here again, it's long natural history of diseases either by its natural history or by the therapies that have been approved that prolong disease.

It could be due to the limited populations, which preclude a randomized trial. And it could be due to the lack of equipoise, which really bands that patients have access during the course of disease. I think a much more important question, and one that we are constantly looking at, is not so much what does an individual drug do to the natural history of the disease and prolonging survival in patients that have metastatic disease, but what is the impact over the years of multiple drugs being approved on the basis of progression-free survival or response rates when they are used either in combination or sequentially.

And we could see that, for example, in multiple myeloma, where the course of that disease has been significantly changed, and patients' lives have been prolonged. And the vast majority of the drugs that have been approved have been on non-survival endpoints. And this is true not only for multiple myeloma, but also probably for renal cell cancer.

CH: Yeah. That's interesting. It's a challenging analysis, of course. But that would be a very interesting, essentially public health roll up of all of these incremental decisions. Right?

RP: Correct.

CH: Yeah. So, as I said before, the OCE has been in operation just over two years. During that time, more than 80 therapies and products have been approved, I think. Right? And there've been more than a dozen guidance documents approved, 60 workshops and symposia for oncologists and for patients.

And there were several of those workshops that we at ASCO were privileged to co-sponsor along with you. This is the favorite child question. But what's your proudest achievement so far?

RP: A difficult question, but an easy question, too. It's about the people that work here and the patients that we serve. And I think my brightest moments are when we see the development of our people coming in and taking leadership positions both within the agency in a regulatory context of their job, but also in the academic fields and participating in conferences, publishing papers, and really finding enjoyment in the job that they have outside of the day-to-day regulatory activity.

One of the things that I have always emphasized since I came here 20 years ago from an academic medicine position at M.D. Anderson is really to give the agency a much more academic perspective. And I've always stated that I think we do much more academic work here at the FDA than many academic centers. And I'm not talking about the generation simply of papers or research grants.

I'm talking about actually critical thinking of what goes on at an application, since we have a multi-disciplinary team of statisticians, clinicians, clinical pharmacologists, toxicologists, manufacturing people that all work together. So it's really about-- my greatest accomplishment is really about the young people that have come in that I've mentored, and really have assumed roles, and really will be my lasting legacy here.

But I also want to emphasize that one of the things that I have repeatedly highlighted to this staff is really to consider the patient in really any regulatory decision. Here again, it's not about a P value. It's not about a primary end point. Granted, those things are important, but we really have to bring together the whole body of information about a drug in making a regulatory decision and making that a patient-focused thing. And as I stated before, at the end of the day will the American patient-- will the American public be better off with this drug than without it?

CH: Well, Rick, I got to say that's an inspiring description. It makes me wish I were younger, and maybe I could come and be mentored. But alas, it may be too late for me. But we really are proud to work with you, and to work with so many of your staff in many productive collaborations.

I want to thank you again for joining me today for this ASCO in Action podcast. We always appreciate your expertise and your perspectives. And we look forward to continuing to work with you to ensure that patients with cancer have access to safe and effective treatments.

RP: And thank you, Cliff. It's been a pleasure. And here again, I really think ASCO for providing a lot of resources to us in conducting symposium, and really in fostering better cancer care for patients. I think that's the ultimate goal of both organizations.

CH: It sure is. And I want to remind our listeners that you can follow the FDA Oncology Center of Excellence on Twitter. Their handle is @FDAOncology. That's one word. You can follow me @CliffordHudis, and you can follow ASCO @ASCO. For more information on the latest cancer policy news and updates, visit ASCOAction.ASCO.org. And Rick, I'm going to ask you once more to remind the listeners of the way they can access Project Facilitate.

RP: They can learn about Project Facilitate from our website at www.FDA.gov/OCE. And our project facilitate phone number is 240-402-0004. And the email address is ONCProjectFacili tate@FDA.HHS.gov. ONCProjectFacilitate is spelled O N C P R O J E C T F A C I L I T A T E @FDA.HHS.gov.

CH: That's great. So until next time, I want to thank everyone for listening to this ASCO in Action podcast.

Jun 25 2019
31 mins
Play

ASCO President Shares Struggles and Solutions to Closing Rural Cancer Care Gap

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In the latest ASCO in Action Podcast, ASCO’s President, Dr. Monica Bertagnolli, FACS, FASCO sat down with ASCO CEO Dr. Clifford A. Hudis to discuss cancer care in rural America. Improving cancer care access in rural America has been a signature issue in Dr. Bertagnolli’s presidential year, during which she has held town halls in communities across the country to discuss the real-world challenges facing patients in rural America and their cancer care teams. The podcast reveals some of Dr. Bertagnolli’s learnings from her town halls, and she explains what rural cancer care in America looks like today and offers steps to improve rural cancer outcomes in the future.

May 28 2019
29 mins
Play

Ensuring Response to Opioid Crisis Doesn’t Harm Patients with Cancer

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Welcome to this ASCO in Action podcast. This is ASCO's podcast series where we explore policy and practice issues that impact oncologists, the entire cancer care delivery team, and most importantly, the patients we care for, people with cancer. My name is Cliff Hudis. And I'm the CEO of ASCO, as well as the host of this ASCO in Action podcast series.

For today's podcast, we're going to do something a little different. We don't have a guest today. Instead, we're going to spend some time going over a quick update on an important clarification issued recently by the CDC, the Center for Disease Control and Prevention, and specifically, their guidelines for prescribing opioids for chronic pain, a very topical issue.

The clarification they issued was the form of a letter from the agency to ASCO, as well as to ASH and the NCCN. And in this letter, the clarification affirmed that the CDC guideline was never intended to deny access to clinically appropriate opioid therapy for patients suffering with acute or chronic pain from conditions like cancer and sickle cell disease.

But I want to explain first why it was important that they issue this clarification and then talk about what we have to do next. Opioid abuse in the United States is clearly a very serious issue. And the tremendous toll that it's been extracting on individuals and families across the nation is well-reported. Indeed, it was one of the reasons originally given for the passage of the 21st Century Cures Act. In fact, one of the motivations had to do with addressing some parts of the opioid crisis.

And so this just makes the point that finding a solution to the problem is among the very highest priorities that government and really the general public, as well as professional societies and advocacy groups and all stakeholders, have to be working towards. However, we do have to, at the same time, be careful that we don't overreach and cause additional harm, especially to vulnerable populations, as we take steps to reduce opioid abuse. What happened before was that there was a misinterpretation of the opioid prescribing recommendations that had been issued by the CDC.

And this resulted in part in new laws and regulations, as well as third-party payment policies that severely limited essential pain medications from patients with cancer and sickle cell disease. The consequence for them was suffering and even more prolonged hospitalizations and health care expenses.

So the challenge here was to fix this mistake. As we talk about how this happened, I want to take a moment and provide a little bit of background on this. Last spring, about a year ago I think, there were papers published, at least one in particular, that highlighted seeming discrepancies-- and I emphasize the word seeming-- between opioid use guidelines that had been issued by the CDC, the NCCN, ASCO, and others.

To their credit, the NCCN, led by Bob Carlson, responded to this by reaching out to us at ASCO and asking if we would be willing to collaborate on a meeting of the minds to identify what was true and not true in terms of those supposedly conflicting guidelines and then issue some sort of a unified statement to help address the situation.

In November of 2018, hosted here at ASCO headquarters, representatives from ASCO, the National Comprehensive Cancer Network or NCCN, the American Society of Hematology, ASH, and the CDC met to discuss the similarities, as well as the differences, among our various published respective guidelines in the area of managing chronic pain. We also discussed how to more clearly communicate to all of our respective memberships how and when practice guidelines should be applied in patient care.

While discussing the CDC guideline, it became very clear to all of us that it was necessary to issue at some point a clarification on the question of where the CDC guideline applied to patients with cancer and sickle cell. And indeed, the first action item we took after this November meeting was that ASCO, ASH, and the NCCN sent a letter to the CDC asking for clarification.

We're really happy, again, to report that this collaboration worked. Very soon after they received this letter from us, the CDC responded favorably. And in their response letter, they noted that their guideline, that is, the CDC's guideline, was initially developed to provide recommendations for primary care clinicians who prescribe opioids for patients with chronic pain outside of active cancer treatment, outside of palliative care, and outside of end of life care.

So I want to pause for just a second and make very clear the aim of their original publication was primary care docs, not oncologists or hematologists, and the patients they were talking about were by and large not the patients who are seen and cared for in oncologists' offices. So the letter really did clarify that the CDC's guideline was never intended to deny clinically appropriate opioid therapy to any patients with acute or chronic pain from conditions like cancer and sickle cell disease.

But instead, it was intended to ensure that physicians and patients consider all safe and effective treatment options for all patients with pain. And underneath all this remained the shared goal of reducing inappropriate use. Beyond this, the CDC also noted that the treatment guidelines from disease-specific experts-- and that means ASCO, NCCN, and ASH-- should be the guide to treatment and reimbursement decisions in the specific circumstances they cover.

So let's just spend another 30 seconds on this idea. They did issue a guideline. It does apply to the general population. They never intended for it to apply to cancer patients or sickle cell patients. And they further called out in a sense the primacy of the disease special list in terms of the guideline priority.

So it's great that we got this clarification. It's wonderful news. But I would submit to you that it's really just the first step towards ensuring that our patients don't suffer needlessly. So with this clarification in hand, we can and I would say we must act swiftly to correct existing policies that have already resulted in some areas in blanket restrictions on opioid prescribing, again, based on a misinterpretation over application of the CDC guideline. Every single day that goes by, there are Americans who are experiencing debilitating pain that could be avoided with appropriate treatment. We have some evidence for this. In 2018, as you may know, the American Cancer Society Cancer Action Network, that's ACS CAN, reported that 30% of cancer patients and survivors said that they were unable to obtain their prescribed opioid medication because of insurance denials. And that was a significant increase almost threefold from the 11% reported in 2016.

So if you remember what we were talking about a moment ago, here's a set of guidelines that come out. They're not meant to be applied to cancer patients. And yet, we saw that as they were being misinterpreted and misapplied, there was a tripling in the number of patients reporting trouble getting indicated medications, and I mean cancer patients.

Furthermore, 48% of individuals with cancer reported that their options for pain management were being limited by laws, guidelines, or insurance coverage denials. So this was, again, an external hand influencing their care coming from outside of their doctor's office.

And even in states that exempt patients undergoing cancer treatment, there are significant administrative hurdles that are delaying access to much needed pain relief, not to mention that such exemptions often excluded cancer survivors. And survivors can have chronic pain for years sometimes from the disease or treatment. And without that exemption, they would, in fact, be suffering in a way that should be avoided.

So it goes without saying, but I'll say it, that we really appreciate the CDC's leadership on this complex crisis. The agency has rightly noted that the opioid epidemic will continue to need ongoing collaboration and leadership. And we all need this as we work towards resolving the crisis. But they also acknowledge the importance of making sure that cancer patients and patients with sickle cell disease get the care and caring that they need and they deserve.

I'll also point out that the US Food and Drug Administration plays an important role in advancing the use of evidence-based prescribing guidelines so that they are able to more accurately and appropriately direct the prescription of opioids. Former FDA commissioner Dr. Scott Gottlieb recognized this. And we look forward to continuing this important partnership with acting FDA commissioner Dr. Ned Sharpless.

I think it's fair to say that the opioid crisis requires a response that protects the public, limits abuse, and ensures access for individuals who live with severe chronic pain. That's a vulnerable group. Clinicians, legislators, regulators, insurers, guideline developers, and patients have to join forces to make sure that we establish sensible, evidence-based approaches that confront opioid abuse but do not add a new group that suffers unnecessarily. We don't want to have one national crisis become two.

So I want to close by extending my deepest appreciation to NCCN and ASH for collaborating with us to address this critically important issue and to ensure that our respective members are able to provide the highest quality care that their patients expect and deserve.

If you want more information on our efforts to ensure access to appropriate pain control for patients with cancer and our other policy priorities, please visit ASCO in Action on our website at asco.org/ascoaction all one word. And until next time, I thank you for listening to this ASCO in Action podcast.

May 14 2019
12 mins
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The Impact of Utilization Management on Patients and Practices

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Welcome to this ASCO in Action podcast. This is ASCO's podcast series where we explore policy and practice issues that have impact on oncologists, the entire cancer care delivery team, and most importantly the individuals who care for people with cancer. My name is Clifford Hudis, and I'm the CEO of ASCO, as well as the host of the ASCO in Action podcast series. For today's podcast, I am delighted to have as my guest Dr. Jeffrey Ward. He's the chair of ASCO's Government Relations Committee, and a longtime active member in that area. In addition to his important contributions to ASCO over the years, Dr. Ward is a medical oncologist and a hematologist at the Swedish Cancer Institute in Edmonds, Washington.

Our conversation today will focus on utilization management in cancer care, or the policies that public and private insurers use to control the use of anticancer drug therapies, such as prior authorization requirements, restrictive formularies, step therapy, or fail first requirements, and specialty specific tiers. These are all new and complex topics for some listeners. For others, there's great familiarity. And we're going to explore all of them in the coming discussion.

In September of 2017, ASCO published in the Journal of Oncology Practice a policy statement on the impact of utilization management practices specifically directed at cancer drug therapies. In that statement, ASCO outlined its opposition to payer imposed utilization management policies that restrict patient access to high quality, high value cancer care. The statement also points to high quality clinical pathways as the best first option for ensuring the appropriate utilization of anticancer drugs and the delivery of the highest quality cancer care.

So with that as introduction, Dr. Ward, I'm delighted to welcome you to the podcast, and really looking forward to hearing your thoughts on utilization management. Thank you for being here.

It's a pleasure. Thanks for inviting me.

So to get the conversation started, can you just define first exactly what we mean by the phrase utilization management? Utilization management is classically when insurers or payers put controls over what care a patient may receive. And in our case, that usually means control of the drug therapies that they're going to get. I think that utilization management more strictly could also include when providers themselves use practices that try to strive for the highest quality care at the best price.

So that already raises the possibility that there are a number of utilization management policies that payers could employ focusing, for example, on the use of specific prescription medications or other interventions. What are some of the more common utilization management practices that are being used specifically in cancer care?

Well, I think the one that we run into every day is specialty care pricing. I was talking to the MedPack folks at Congress just a couple of months ago and began telling them the contortions we go through in a practice, where in my practice, we have seven docs. We have two full-time people who their whole job is to get authorization for drugs, and then to figure out how the people are going to pay for their co-pays that can sometimes be several thousand dollars a month. It's a restriction that I suspect the drug companies actually utilize to try and market their drug by providing co-pay support.

At the same time, I think payers build it into the pricing of their insurance. So it's become a big part of what happens. And it's almost a dance between practices and payers. But it takes a tremendous amount of time and effort. And I'm not sure that it accomplishes a whole lot.

Wow. I mean, I think there's a lot that we could unpack there. And I think for some of our listeners, it would help to frame this in even more realistic terms. We shouldn't use specific drugs or drug names. But I'm curious if you could provide a more concrete example of what exactly would happen to Mr. Smith in your office when you make a recommendation for a treatment, and what then ensues in terms of this specialty tier pricing.

Sure. So Mr. Smith has prostate cancer. And he is appropriately treated with a very expensive oral medication along with his castrate therapy. And in doing so, I write a prescription. I send that prescription to a specialty pharmacy.

They then begin doing a preauthorization process, or that preauthorization process may be done from the doctor's own office. They get preauthorization for the drug, but they find out that the patient has a 20% co-pay. This drug may cost $12,000 a year, and so the patient is now responsible for the other 20% of that cost. If it is a commercial payer, then the patient will-- then the specialty pharmacy will go to the drug company, and the drug company will provide co-pay support. That requires often the patient to give them a copy of their last tax return, and there will be some other requirements to show that they don't have the ability to easily pay for that co-pay.

If that kind of process wasn't in place, the patient would probably in many circumstances deny the treatment and not get the best care that they deserve.

If it's a Medicare patient, then the drug company directly providing co-pay support is called fraud. And so in that circumstance, the pharmacy will then-- or the practice will turn to foundations that help provide co-pay support, and try and get the patient foundation support. You're better apt to do that in January or this time of year in March than you are in November, December, because foundations tend to run out of money.

So you run around scrounging up foundation support for your patient until you're able to do it. That puts delays that can sometimes last weeks before you can initiate a treatment. And not to put too fine a point on it, but in this example, you recommended a specific therapy, and ultimately the patient getting it, the delay is really in scrounging up or managing the co-pay through these various channels. Is that a fair assessment of what you've described? Or did I miss something? That's exactly right. And so the patient will almost always get the drug, but there can be considerable delays.

OK. And so that answers, in a sense, the next question, that the concern about the overall impact of this kind of approach on individual patients is a delay in terms of needed therapies. And sometimes that might be a critically important one, but other times it might be honestly less critical.

But it's also a lot of work. And there's a lot of expense on the side of the practice in navigating this. Is that also a fair assessment? Yes. And none of that is, of course, reimbursed. It's become an expected part of practice, but it is a burden on practices. OK. And just out of curiosity, what do you think the alternative would be? Since all of this seems to boil down to the fact that there is co-pay, and there are multiple ways of mitigating the impact of co-pay on the actual individual patient. What would the alternative to this actually be?

Well, I think in a perfect world, the alternative would be that the patient would not have the co-pay, and the drug companies would admit that they're actually lowering their price significantly when they provide co-pay support. And patients would pay less. And we wouldn't have to go through the dance now. That seems, at this point in time, unrealistic. But I think that right now, the payers really have this locked into their cost of their insurance. So it is a dance that's expected. If there was a way to get rid of that, that would be great. One suggestion that has been made is that part D drugs that are cancer drugs actually get moved to part B, and that they get paid for that way for Medicare patients. And then the co-pay issue with part D drugs goes away for the Medicare patients. And then maybe some policy might follow on the commercial side. Maybe not, right?

Yeah. That may follow. But the commercial side is a little bit easier, because the commercial side, you can get direct support from the pharmaceutical company for their co-pay. And you can't do that for Medicare patients.

OK. So let's-- forgive the pun-- take the next step and talk about step therapy. As I understand it right now, the White House and Congress, along with ASCO and other stakeholders, we are all working-- and I think it's true at this point in a fairly collaborative way to try to talk about and start to address the high cost of prescription drugs here in the US.

One part of these efforts from CMS has been to propose expanded use of step therapy. Can you describe what step therapy would look like for a patient with cancer?

Sure. I think that some of us prefer the word fail first to step therapy, because that's more descriptive of what it is. Step therapy is the idea that before you can get drug B, you have to use and fail drug A. Most step therapy is based on price of the drug. And we don't think that that applies very well to cancer patients.

Most of our patients, there is a best drug for them. And to have to use inferior drugs to get to the best drug is problematic, not just in time and delays, but we know that our disease evolves over time. And if you use an inferior drug first, the superior drug may not work nearly so well as a second line therapy.

So in an ideal situation, hypothetically, were there two drugs that on average offered the same response rate, progression free survival, overall survival, and similar toxicities where one costs less than the other, this approach might make sense, assuming there weren't mitigating factors at the individual patient level. And it's fair to point out, I think, that in other domains outside of oncology, classically blood pressure management, step therapy has been accepted and is reasonably successful.

If I'm hearing you right though, the problem we see in oncology is that kind of ideal equivalence is rare. And most of the time there really are reasons, good reasons, defensible evidence-based reasons, that oncologists select one treatment or another. Is that a fair summary?

Yes, I think it is. An example where someone I think might inappropriately use step therapy would be in renal cell cancer, where we have a number of TKIs that are available. Someone may say that they all have similar response rates. Of course, none of them have been compared head to head. And so that makes it very difficult to say whether they're really the same or not. But they do have different toxicities. And so even if you would say on average their toxicities are similar, for a given patient, one drug may be better tolerated or more appropriate than another. To use those drugs in a step therapy fashion would be inappropriate, and I think would harm patients.

There are circumstances where I think step therapy is easy to apply in oncology, but they are few and far between. One example where step therapy I think will be applied-- and I wouldn't have problems with it-- is in the biosimilar products.

And my understanding then is that the Medicare Advantage, at least, some of the plans began allowing step therapy just at the beginning of this year, 2019. Have you begun to see or hear about any impact on patients yet as a result of that or is it still too early? I have seen payers doing some step therapy in, for example, the biosimilar realm, or even requiring you to use a filgrastim instead of pegfilgrastim. But I have not yet seen the part D payers using step therapy. I don't know whether ASCO and its state affiliate counsel has begun gathering examples across the country otherwise. The filgrastim-pegfilgrastim issue that you just mentioned, I think, is a good one for highlighting some of the subtle challenges here. It's probably fair to say that the impact on hard measures, like infection or admission to the hospital, will be indistinguishable. But in one case there are multiple either office visits or health care professional interactions or a burden on the part of the family members or patient for regular administration, whereas with the other choice, of course, there's one dose per cycle. So the price, if you will, of that convenience, I think, is another issue that will eventually bubble to the surface. Right?

Yes. And the ironic thing about that step therapy is that if a patient decides that they want to self-administer the drug at home, they have to pay co-pays for the privilege of giving themselves a shot. Right. Well, we could probably fill the whole podcast with perverse incentives and bizarre quirks of the system, I'm sure, in terms of drug administration, right?

I think that that's one of our problems.

So look, we've identified these challenges. Of course, our job here is both to highlight them so that our members and listeners are aware, but even more importantly is to do something about that. So can you start to describe how ASCO is working with Congress and the administration to address some of these issues to encourage policies that would be better for people with cancer?

Well, I think one of the first things that we've done is we've collaborated with our state affiliate societies in individual states where there has been legislation regarding some of these utilization management activities that don't make a lot of sense. There are a number of bills last year in just step therapy itself. In a number of states, I think there were a total of about 90-some odd bills that addressed some kind of utilization management in different states across the country last year.

We have a similar bill that's in the legislature here in Washington state right now that is looking at step therapies, and to put some curbs on it, and more particularly, to make the processes transparent so that when you do have a step therapy in place, you know it. You understand it. And you know what literature has been used so that you have an ability to appeal it if it's appropriate for your patient. So those kind of processes ASCO is facilitating. The big picture, I think, is that we need to somehow develop a reimbursement system that actually incentivizes oncologists and payers to work together instead of being at odds over this. And that would involve developing pathways that are value based, but in our mind, very distinct from step therapy.

Well, I mean, that's a natural segue to the next topic, which is, in fact, ASCO's 2017 policy statement, which addressed utilization management, and pointed to high quality clinical pathways as payers best first option for ensuring appropriate utilization of anticancer drugs. Can you talk a little bit about why we at ASCO have turned to focus on that as the tool to drive the delivery of high quality care?

Well, I think there are several reasons. One, we've staked out a position that we believe that as oncologists we should be responsible for the way we use drugs, and the management of our patients' care, and that part of that responsibility should be to be cognizant of the cost and the value of the drugs we give.

But we don't believe that we should be responsible for the prices that those drugs carry. A system that we have right now in buy and bill makes us responsible for that. And many of the reimbursement reforms that have been done, the oncology care model being one of them, for example, actually makes oncologists responsible for the cost of the drugs in the reimbursement scheme. We think that that is a mistake, and that there are better ways to try and leverage the cost of drugs than making us responsible for them.

Right. I mean, one of the things we say is that we don't set the launch price, and we're not responsible for it. But in these models, it can be the case that expensive new drugs that drive up the cost of care even when they do deliver better outcomes and are the right therapy can become a financial liability for the prescriber, right? And that's a real challenge, I think, for us.

Correct. I mean, I was a lead author on a paper that we published a year or so ago in the Journal of Oncology Practice that used a model to demonstrate what the risks of taking on responsibility for the cost of drugs in a model like OCM would be. And in doing so determined that if you were a small practice of less than 10 doctors, there was a 10% risk that you could have a 30% deficit in your drug costs just on the basis of who happened to walk in your door. The end result would be that if you were in that kind of arrangement and taking on risk for the cost of your drugs, whether you were successful or not would depend less on the skill and the choices you made, but on who walked in your front door. Yeah. And that's a real problem, because we certainly don't want a system where there's an incentive and disincentive to select or select against certain sick patients, obviously.

So I guess the one question that some people may ask as they think about this is whether there are any situations where the utilization management policies we're seeing now do provide a benefit. That is, are there patients or outcomes that are improved because of the current utilization management tools? Are there places where costs are controlled or there's more effective management of resources in general? Meaning, are there any silver linings in this right now? I think that for individual payers, particularly large payers, there may be a silver lining that we don't see. So I'm guessing as to whether this exists or not. Many of them, I believe, get rebates, often volume rebates, based on step therapy. Whether that actually computes into lower premiums for patients or not or simply higher profits for the insurer, that would be well out of my realm of knowledge.

But I think that there is some leverage. I think there'd be a better way to develop leverage. And that would be if we were using routinely value-based pathways and partnering with insurers to be able to put downward price on drug-- downward pressure on drug prices.

Right. So alignment of incentives is what you're describing at the end there. And I think that's ultimately the best solution for many of the problems that plague us in the health care system. With that, I want to thank you, Dr. Ward, once again for joining me on this ASCO in Action podcast. It was a real delight to hear your thoughts, and to gain a little bit of deeper knowledge. Thanks for doing that.

You're great. It was fun to be here.

For listeners who want more information on utilization management policies and the latest cancer policy news and updates, visit ASCO in Action, which is literally ascoaction.asco.org on the web. And otherwise, until next time, thank you for listening to this ASCO in Action podcast.

Apr 16 2019
23 mins
Play

Joint Assessment of ASCO, ESMO Value Frameworks in Focus on ASCO in Action Podcast

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Dr. Clifford A. Hudis (CH): Welcome to this ASCO in Action Podcast. This is ASCO's podcast series where we explore policy and practice issues that impact oncologists, the entire cancer care delivery team, and the individuals we care for-- people with cancer. My name is Cliff Hudis, and I'm the CEO of ASCO, as well as the host of the ASCO in Action Podcast series.

For today's podcast, I am really delighted to have Dr. Lowell Schnipper, chair of ASCO's Value of Cancer Care Task Force as my guest today. In addition to his extensive service to ASCO, Dr. Schnipper is the Theodore W. And Evelyn G. Berenson Professor of Medicine at Harvard Medical School, Chief of the Division of Hematology/Oncology at the Beth Israel Deaconess Medical Center, and Clinical Director of the Beth Israel Deaconess Cancer Center. He is also an Associate Director of the Dana-Farber Harvard Cancer Center and a member of the Cancer Center's Executive Committee.

Now, to provide some background for our listeners, I do want to highlight a couple of related points. First, as early as 2007, ASCO, led by Dr. Schnipper, was already focusing on rising drug and health care costs. And two, as detailed in our five-year strategic plan, almost everything we do at ASCO is aimed at helping our members and all of society achieve high-quality, high-value care for all people with cancer. Examples of the latter include our Patient-Centered Oncology Payment model, our participation in the Choosing Wisely campaign, our entire CancerLinQ project, and ASCO's Quality Oncology Practice Initiative, or QOPI, which is now available internationally.

So our conversation today will focus on one longstanding project that's part of all of this effort. And this is one that's been a critical component of our efforts going back really, starting in 2007, ASCO's Value Framework. Here, I want to note that both ASCO and ESMO have developed algorithmic scales that are designed to evaluate the benefit of new cancer therapies.

Again, ASCO's is called the Value Framework. And it was developed primarily as a physician-guided tool to facilitate shared decision making by patients and their oncologists as they select among high-value treatment options for individual patients. In our framework, the clinical benefit of a specific treatment and its known toxicity are combined, and they produce a score that we call the Net Health Benefit.

So after years of building, testing, and refinement, we recently conducted an analysis that compared the output of ASCO's Value Framework against the European Society for Medical Oncology, or ESMO's tool, which they call the Magnitude of Clinical Benefit Scale.

Dr. Schnipper, you co-authored the assessment that we're going to discuss today. And that's why I'm so delighted to welcome you to the podcast. I want to thank you, in advance, for sharing your insights with us here today. Thanks for joining us.

Dr. Lowell Schnipper (LS): It's my pleasure to join you. This is a terrific opportunity to explain a bit about what ASCO is doing and put it in the context of what other groups are doing, in particular, a group like ESMO. We started this effort, as you were pointing out, approximately a decade ago, not the Value effort, but our emphasis, as a society, on the increasing cost of cancer care for our patients.

And we wrote several manuscripts detailing the importance of doctors being sensitive to cost and, of course, providing the patients with the best opportunity for high-value care. As the years evolve, and some of the initiatives that you've already mentioned, Cliff, we felt it really important to develop a formulaic way of approaching how we, as an oncology community, might assess the clinical value of the drugs we use to treat patients with cancer and convey that, then, to our patients in the context of shared decision making.

That's really the background of this effort. And the Value Framework itself has actually evolved over about three or four years in a number of iterations. And I'm hoping that as the discussion ensues, we'll be able to get into that in more detail.

That's great. So let's actually start with the main topic today, which is the comparison between ASCO's work and ESMO's. Why, exactly, did you decide to pursue this comparison and then publish it?

We became aware that ESMO was undertaking a very similar initiative, namely an attempt at developing an algorithm with which to assess the value, the clinical value, of oncologic therapies representing all of the European nations. That's about 27 nations. In parallel, but actually quite independently, we at ASCO were developing our own Value Framework.

And as one can see when reading about either of them, in many ways, they're quite different. But they have overwhelming similarities, specifically based on assessments of how much good a given therapy does for the patient when compared with a control treatment and, of course, how negative any of the effects of our therapies are to that patient population. And we integrated that, at ASCO, in our Value Framework in a concept that you rightly referred to as the Net Health Benefit.

Well, ESMO, we came to learn as we were readying to publish our framework, that they had worked on something very similar, looking at clinical benefit and toxicity somewhat differently. And they, of course, published theirs in the Annals of Oncology. And we published our framework in the Journal of Clinical Oncology.

These frameworks were met with an enormous amount of interest by every component of the oncologic community. And by that I mean patients, of course, are exceedingly interested in this. And we can get, I hope, to the patient perspective in a little while. But in addition, manufacturers were quite interested in how we were going about assessing the products that they bring forth and we put into clinical trial.

And of course, ultimately, the oncologist, him or herself, is the deciding factor in recommending or not recommending a particular therapy. So we elicited tremendous interest. And I didn't even mention the payer community which, of course, was very, very interested because of the rising cost of oncologic therapies.

In fact, I will say that one of the motivating factors for the ASCO community, and I think for the ESMO community as well, is the awareness that oncologic therapies are very, very costly, sometimes eliciting huge out-of-pocket payments for our patients. And now, I speak for the American health consumer, not so much those in Europe. And this becomes a major factor in the patient's and the patient's family's well-being, as in this risk we know for financial toxicity.

So we felt it very important to establish points of overlap and similarity, as well as points of difference with the ESMO framework in order to understand and improve each other's work. And so while we don't view this necessarily as a planned collaboration with which we'll modify each of ours after arguing about different points in a scholarly way, what we really wanted to do was see how each framework performs when looked at through the same lens of a number of trials.

And so that led to this comparison of, well, we started out with over 100 trials and focused on 97 that were being done in a prospective randomized clinical trial context for palliative purposes, meaning for non-curative situations. And that really is the background of how it came about.

CH: So before we dive into that aspect of the results, I think it might help to clarify, for just a moment more, the comparative effort on two planes. On the one plane, which you touched on, there is the actual design of the tool, what it takes into consideration, and what it weights. And on the other plane, there is how it actually evaluates specific treatment options. So can we just circle back, for a second, at a high level, what is it about the two tools that you would say is similar to overlapping? And what is it that is, perhaps, different, if anything, about the two tools methodologically?

LS: Both tools are premised on using a prospective clinical trial in which a comparator is compared in a specific clinical disease setting, clinical cancer disease setting, with a test agent, or a test regimen. And so both of them look at that particular subset. And, in fact, that is the case for these 97 trials that I just alluded to.

The ASCO clinical benefit, when comparing a test regimen to a control, is literally measuring the difference between the two in the hazard ratio, or the overall survival. So, for example, if the overall survival is measured in months, but no hazard ratio were given, if the overall survival for the control was 10 months, and the overall survival for the test agent was 20 months, in fact, we would register basically a doubling, or a very high degree of clinical benefit.

And if the hazard ratios are such that there's a very low hazard ratio for death, meaning a high likelihood of survival, then the ASCO Clinical Benefit Score would register a large number, accordingly. Our attempt at finding, numerically, the difference between a clinical comparator and a test regimen differs from ESMO where they have reduced categorical differences. In other words, they ultimately arrive at a score of 1, 2, 3, 4, 5 rather than measuring the quantifiable difference between the comparator and the test agent.

So we actually differ in how we go about defining the clinical benefit. We are trying to be a little bit more precise. And ESMO, I think, feels that that attempt at precision may not always be completely valid, because studies vary in terms of sample size and that could influence the variability around the mean or the median. So there's some technical differences, or biostatistical differences.

But basically, we each are trying to develop a magnitude of clinical benefit and have done so in our frameworks. We differ from ESMO in the sense that we have developed a rather elaborate toxicity scoring system. And that's largely because we have, in developing the framework, interviewed many, many patients or leaders of advocacy groups.

And they impressed upon us that it's not just grades three and four, or heaven forbid, grade five toxicity that worries them. It's often low level of chronic toxicity that also impacts on the quality of their lives. And we felt we needed to develop a tool that reflected the patient's perspective as it was explained to us.

And so we have a much more elaborate, and I will confess probably more difficult to pull out of the literature and score, than the ESMO toxicity assessment in which they more or less say, this is highly toxic, not so toxic, or very minimally toxic. So we feel that we needed to do that and that it makes sense because it reflects our patient's input. And again, this is a tool we keep coming back to that's to help patients and docs make decisions. So those are a couple of the ways in which we actually differ appreciably.

In addition, ESMO practically ignores progression-free survival, which, as you know, many, many prospective randomized trials use as a primary endpoint. I think we, at ASCO, completely agree it's not the very best surrogate endpoint. And as such, if [INAUDIBLE] namely, the better endpoint, is not the primary endpoint in a given trial, we will utilize the progression-free survival in our value assessment, but we actually downgrade its value.

So, in other words, if the value of a score for overall survival as opposed to the value of a score for progression-free survival differs, we indicate it by about 20% less for progression-free survival. So the differences in the toxicity parameters we felt were important to maintain and the difference in the progression-free survival measurement, or I should say downgrading its importance, that, too, was also difficult to at least-- well, I should say progression-free survival turned out to be a less valuable endpoint than overall survival.

And we felt quite legitimized in reducing it. ESMO agrees, but they basically give very little credit for progression-free survival unless the improvement in progression-free survival is associated with virtually no toxicity. So we differ a little bit in that. But again, we're circling around the same sets of variables, but coming at them somewhat differently.

CH: All right. So let's talk about the results for a moment. That background, I think, is really helpful to audiences who are trying to put these in context. But a couple of points that I would make, and then I have a question, or maybe one point I would make is, there have been a number of prior studies that have been conducted by external researchers.

They've looked at and compared the two frameworks. And they reported lower levels of agreement between ASCO and the ESMO frameworks than you and your colleagues are reporting now. What's fundamentally changed? I mean, how was your analysis performed? And why does it show a greater degree of concordance than earlier external investigators found?

LS: I'm glad you asked that. That's a key question. And of course, we were initially kind of dismayed when we saw published results in which there was some degree of disagreement between the ASCO and the ESMO scales. Well, it turns out that there was one, out of about four or five that were in the literature, that actually found a high degree of concordance, although it looked at a relatively small number of trials within the same disease area-- lung cancer.

So what we realized was that these are complicated frameworks to work with, that they're not trivial. And the reason I arrive at that is because we are blessed with a very, very bright, talented staff within ASCO who embraced the task of applying our Value Framework to these 103 trials. What we learned is that for people who weren't involved in generating the framework, but were called upon to apply it, they literally had to get onto a learning curve in order to produce consistent assessments after culling out the relevant data from a given paper.

So we are pretty sure that the low levels of concordance really had to do with people misapplying the scales in many, many cases. And the proof of the pudding, I think, is in the eating because while we didn't find perfect concordance, and that gives us additional food for thought, we actually did pretty well, because 65% to 70% of the trials actually came out with an agreeable scoring, meaning that what ESMO concluded was reasonable to recommend incorporating into a European nations Pharmacopoeia for cancer drugs, represented the upper half above, let's say, a Net Health Benefit score of 45 for ASCO.

So those 65%, 70% of trials actually scored pretty much concurrent with one another in terms of identifying drug regimens as useful. The outliers, those that differ, were actually another cause for our scratching our heads and, ultimately, teasing apart the differences. And we do understand some of the reasons why the scales are different, which isn't to say one is better than the other, but it probably just rests on bedrock assumptions in terms of incorporating various variables into the Value Framework.

CH: So that's great. A couple of follow-up questions, I suppose. And I'm just curious, either from the ASCO side or, if you know, from the ESMO side, based on this effort to compare them, is there any plan to actually tweak them to increase their alignment? Or is everybody happy that they're each fulfilling their planned functions and this little bit of discordance is OK?

LS: That's a great question. I can say that, at the very start, this goes back a couple of years, I had meetings with counterparts at our annual meeting, or at the ESMO meeting, just talking about whether or not it would be desirable to essentially arrive at a transatlantic consensus of what would be thought to be a clinically useful addition to our Pharmacopoeia versus not. And I think we are all motivated by exactly that, although I think we don't necessarily have a plan at the moment to try to develop a single uniform framework, at least not for the foreseeable future.

And the reason for that is that we are trying, in the US environment, to utilize our framework in some of the organs that we, as oncologists, typically go to in order to assist with clinical decision making. And so here, I'm referring to the JCO when we publish prospective randomized trials or, for that matter, other high-impact journals like New England Journal of Medicine or perhaps JAMA. We would like to actually begin a catalog of ASCO Value Framework Net Health Benefit scores as these trials accumulate over the next 6 to 12 months.

And that's because we'd like to actually get a feel for that which oncologists are comfortable using and recommending to patients and how our Value Framework stacks up against that. We're thinking that that could be a very, very helpful way of us understanding if we're throwing fastballs right over the plate, or are we missing the mark sometimes and do we need to make some mid-course corrections.

And as you can imagine, the Value Task Force, at the moment, is viewing where we are with the framework as pretty far down an iterative process that's not yet complete, because we need to incorporate this assessment into the real oncologic literature, see how well it performs with what doctors think and patients think are useful drugs. And at that point, I think, we'll be able to utilize it more effectively.

The other thing that I will say that we need to do, and we already have a sub-task force or a subcommittee working on this, is to essentially address the issue of, in breast cancer or in colorectal cancer, if there are three or four trials for a given specific clinical scenario, but each is using a different comparator, a different control, can they ever be compared if the test agents are the same, or the test regimens are the same?

And the answer is, of course, they really can't because you can't easily do cross-trial comparisons. And so we have been working with methodologists who are advising us on doing network meta analysis, a way of at least statistically looking at trials in the same patient population testing the same regimen or novel agent, but if using different controls, to essentially come up with what amounts to a reasonable sort of summarize, or summative control, against which we can then look to see how impactful a new therapy is or is not.

Statistically, it's never all that pleasant, as you know because you're a very experienced investigator, it's never all that easy to even think about cross-trial comparisons. But rigorous statistical techniques, I'm told, are available to at least help us do that.

CH: Yeah, it's interesting. There's a little bit of overlap with the synthetic control arm discussions we have in the context of CancerLinQ. But that's probably a topic best left for another day. I want to come back, though, to a core issue that I think circles all of our discussion and that is financial toxicity, which you raised earlier. And very specifically, in your dreams, how do you see that this process, both our tool and ESMO's for that matter, how do you see them actually having an influence on drug price, which is, I think, fairly summarized as the elephant in the room here?

LS: I'm glad you asked that, but I continue to struggle with what I would think would be an acceptable answer in its broadest dimensions. But my sense is the following. There has been incremental improvements in cancer therapy from the very start of our field. And you'll remember in Charles Moertel's work, the increment of 5-FU in colon cancer was trivial, a few months.

But now we know that patients with metastatic colon cancer can survive for 27 months, on average, perhaps more in many cases. So how do you judge incremental benefit? That becomes a real thorny, almost a societal issue because therein lies the rub. We know our patients are being almost asked to pay out-of-pocket quite a substantial sum for many of the novel drugs that we have.

Some of them, you and I would absolutely agree, are a slam dunk benefit. But we know, as well, that there are many that add very, very small degrees of benefit in comparison with a much more affordable, perhaps generic drug, or set of drugs. What I have hoped for is that if we arrive at what our peer group, the oncologic community and patients, feel is a credible value framework that market forces will be able to get to work and actually modulate what the price that's being asked for a given drug.

And that really goes back to the first thing we wrote in 2009 when we issued a guidance statement from the founding members of the task force. And that is that we recognize that oncologic drugs and, in fact, health care, in general, is not a market in the usual sense of the word. And the fact that it is a perverse market makes us worry, if ever, we'll get to a point where if we can show value, that will be reflected in the cost of the drug.

If you have an innovative drug that is a slam dunk, like trastuzumab, of course, that should have and merit lots different value than a drug that has a very small incremental benefit. And how that can be reflected by a value framework influencing a real world market scenario I'm hopeful about, but I don't quite know the path to get there.

CH: Yeah. I think that's actually a great summary of the frustration that so many of us feel as we think about how rational market forces should work and then what we actually see in our reality. So thank you for at least trying to put this in perspective.

Thank you. It's been my pleasure to participate. And I'm really happy that ASCO is producing vehicles like this to broaden the understanding of the efforts that we're undertaking.

As we wrap up, I want to just remind our listeners that the joint Value Framework assessment that we've been discussing is available online. You can find it at ASCO.org/value. And the ASCO Value Framework is, again, as I said in the introduction, just one part of ASCO's broader and multifaceted effort to help all of our members, and everyone, achieve high-quality, high-value care for people with cancer.

The other efforts that we touched on before and you hear about in the podcast series at various times are the Patient-Centered Oncology Payment model, the Choosing Wisely campaign, CancerLinQ, and ASCO's QOPI, or Quality Oncology Practice Initiative. For more information on any, or all, of these initiatives and for the latest cancer policy news and updates, I ask you to visit ascoaction.asco.org and you can find links out to these programs and more there.

Dr. Schnipper, I want to thank you again for joining me today for this ASCO in Action Podcast . And for everyone listening, until next time. Thanks for joining us.

Mar 26 2019
29 mins
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Exclusive Interview: NCI Director Talks Big Data, Clinical Trials, the Cancer Research Workforce—and Why He Lives to Conquer Cancer

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Dr. Clifford A. Hudis: Welcome to this ASCO in Action podcast. This is ASCO's podcast series where we explore policy and practice issues that impact oncologists, the entire cancer care delivery team, and the individuals we care for-- people with cancer. My name is Clifford Hudis, and I'm the CEO of ASCO as well as the host of the ASCO in Action podcast series. For today's podcast, I am delighted to have as my guest Dr. Ned Sharpless, the director of the National Cancer Institute.

The NCI is the largest funder of cancer research in the world, and it has helped to drive many of the major prevention and treatment advances we've seen over the past 50 years. This includes things like HPV vaccination and the identification of the link between HER2 status and breast cancer outcomes and treatment, as well as new discoveries that have dramatically improved outcomes for childhood cancer.

Dr. Sharpless, welcome, and thank you for joining me today. Now, we really have a whole lot to discuss, but before we get to our planned topics, I have to jump ahead and start with the president's State of the Union address, when President Trump mentioned that he wants to see $500 million appropriated for childhood cancers over the next decade.

Can you talk a little bit about how you expect that, specifically, to play out? What will the NCI be able to do with those new specified funds for pediatric research?

Dr. Ned Sharpless: Sure. I think childhood cancer-- childhood cancer is an area where the National Cancer Institute has had a long interest and a robust portfolio of research. And I think it is an area where we've made some progress, in terms of mortality, over the last few decades. But you have to say two things about childhood cancer. While progress has been good, and we're making-- more kids are surviving cancer therapy today than ever-- there's still a long way to go. Too many kids dying of cancer in the United States, and even the kids that we're able to cure have these significant lifelong survivorship challenges, in some cases.

So the therapy that is curative may leave patients with side effects of surgery and chemotherapy and radiation for the rest of their lives. So better treatments for kids and less toxic treatments for kids are what we are really looking for. And with that amount of money, I think a good-- the thing that it appears to me that one could do to most quickly move the needle in childhood cancer-- which, as you know, is a collection of less common cancers, even rare cancers-- is really a more intentional effort at aggregating and using and linking clinical data with molecular data and other sorts of patient data, so that we can really learn from every child with cancer in the United States, so that we can really figure out what's working in certain populations and then disseminate that information as rapidly as possible-- without having, in all cases, to rely on slower clinical trial structures that are challenged for certain populations where accrual can be difficult.

So I think that is the vision for the president's initiative, is to, with additional funding, allow for very aggressive, intentional, and organized data linkages and data aggregation so that we can learn from every trial and therefore treat every child's cancer in a better, more effective way.

Dr. Clifford A. Hudis: You know, I think that's great. And that actually provides two different segues-- one I'm going to pick up right now, and one I want to come back to. The first is about data-- big data, specifically. We'll come back to that. The second is about the way the pediatric oncology community for years has really led in designing studies that could accrue the majority of children diagnosed with various specific diseases.

And that leads me, that idea of eligibility and the structure of research, to ask about the way that you're thinking about modernizing clinical trials. This is something I know you wrote about in JAMA Viewpoint in the last couple of months. You addressed financial pressures, the need to increase overall rates of accrual to the trials, especially representing patients from underserved populations. Can you expand a little bit on that effort and what kind of progress you see as possible in the coming months and years?

Dr. Ned Sharpless: Yeah, I think everything we do successfully in cancer today is in some ways the results of a clinical trial. And this is clearly one of the most important things the NCI does, in terms of moving basic science into patient care through experimental clinical trials. And it's an area where we-- frankly, a lot's changed in the last couple of decades. When I was a wee fellow, the clinical trials apparatus was very different from the way it is 20 years later today. And we need to make sure that we modernize the clinical trials process to keep up with the changes in our understanding of the biology and the new kinds of therapy we have for cancer.

So that brings up a bunch of items that are areas where the NCI is really doing a lot of things. So, for example, one of the first problems I noticed when coming to the National Cancer Institute was that the clinical trials infrastructure, the big networks that we have for doing these kinds of trials, were under-resourced, that they had a funding problem. And they were becoming non-competitive with the trials sponsored by industry.

And this showed itself in many ways, in accrual fees for patients, or the wait times to get the trial open, or the slow accrual once the trial was open. And so they were laboring under a number of problems. And so we decided we had to invest in the Clinical Trials Network and have been doing that and will be continuing to doing that in a number of ways-- through direct funding to attempt something like the National Clinical Trials Network or the NCORP, for example, the NCORP organization, but also by additional funding for biobanks and data aggregation initiatives, targeted clinical trials, et cetera.

I think we've also-- there are some structural problems with the clinical trials that you alluded to. For example, eligibility criteria, I think, hadn't really kept pace with modern clinical trials. And I think ASCO and other groups have played a really important leadership role in identifying what are good eligibility criteria and which ones are not as necessary anymore.

And then, do we have to have the same criteria in all the trials, and be more thoughtful about how those are used as a way to enhance accrual, because often we have a-- superfluous eligibility criteria can limit accrual. And increasing accrual by a variety of measures is really important. And we've thought a lot about how to do this through novel ways of clinical [? house ?] matching.

I think one of the more successful efforts we've had in clinical trials accrual recently has been the MATCH trial, the NCI MATCH trial, which was able to accrue 6,000 patients at 1,100 sites in the United States, filling a targeted accrual two years ahead of schedule. It's the fastest-accruing trial in the history of the NCI.

And I think one of the things MATCH teaches you is that if you have an interesting trial that's written in a nimble way that is open in the community-- that patients don't have to drive six hours to a cancer center, but can go to a local NCORP site, for example-- then those trials will accrue. We can accrue quickly, and we can accrue underserved populations, and we can accrue rare cancers. And that framework is more nimble than, say, the large phase III randomized trial run only at cancer centers that we had 10 years ago.

There is still a role for large, randomized, phase III trials. The NCI is not backing away from that, or where we will support those. But I think, as we discussed in the JAMA piece, we really have to be thoughtful about where the NCI needs to be involved with those kinds of trials, compared to which of those should be supported by industry, for example.

Dr. Clifford A. Hudis: It sounds like you're alluding to something I think you and I discussed even when you first got into your current role, which is the identification of those trials that industry should run, essentially, itself, and those trials that the NCI should support as complementary to industry trials. Can you expand a little bit on how you see that distinction and where you draw that line?

Dr. Ned Sharpless: Yeah, the thing to know about clinical trials in oncology in the United States right now is most are actually paid for by industry. There's a huge pharmaceutical industry spend on clinical trials, and from my point of view, that's great. The fact that industry is paying for trials to develop therapies for cancer patients-- that's less money the NCI has to spend on those same questions. So we think that's a wonderful development and healthy for cancer research.

But if that's the way it's going to be, then the NCI has to ask itself-- for the precious moneys that we have to spend on clinical trials, we need to use those in a way that's maximally effective and, in particular, not duplicative with what industry sponsors are doing. It's important to say, we do a lot of work with industry. So it's not just us either-or.

Many of our trials, through these agreement processes called CRADAs, allow us to do trials with pharma sponsors and use their compounds in our trials. And that's a real boon to our research effort, as well. But there are certain kinds of trials that are very important where we really want to know the answer, but they're a bad fit for what industry is going to fund.

For example, a de-escalation trial-- that's a trial where there's a standard of care that's pretty good, but the therapy is toxic. And so we'd like to see if we can get the same good outcome in a population using less aggressive therapy. A very important example of this was the TAILORx trial recently, where we showed that based on a genetic risk score, an RNA-based risk score of the breast cancer, women with estrogen receptor positive breast cancer-- many of them could forego cytotoxic chemotherapy and just take anti-hormonal agents and have the same good outcome in terms of their long-term survival.

So that's a trial that is not going to be industry-led, for a variety of reasons. But I think it is the kind of question that's really important for patients. It's important, also, to say that de-escalation trials are hard to do. They require a lot of thought. They don't always work. And so they require these comprehensive thoughtfulness and infrastructure that the National Clinical Trials Network can provide.

So an additional example is these multi-modality trials we have, where maybe two different agents come from two different pharmaceutical companies, and then there's some surgery and some radiation. There's very complex, multi-integrated care. And those can be very hard for a single sponsor to run, but, again, can be a very good fit for the NCI. And there are many other examples like this.

But I think the real question we have to ask is, if our budget is limited and finite, what are the trials that the NCI really should do and lead on?

Dr. Clifford A. Hudis: Yeah. And I think one of the points there is you need to conduct-- we need to conduct-- trials as efficiently as possible, getting the most so-called bang for the buck. You alluded to the fact that the NCI, along with ASCO, has been working on making trials essentially more efficient by making them more representative of the actual cancer population we end up treating.

And a specific area of focus for us at ASCO, in this collaboration and also in our TAPUR trial, has been driving the eligibility age down below 18. My understanding is that this is something that you're adopting as a recommendation across the NCI, as well. I guess my question is, how broad and how quickly do you expect to see this implemented?

Dr. Ned Sharpless: We have a number of efforts related to these barriers to accrual. You mentioned age as one of them and other sorts of exclusion criteria. And we've looked deeply and thought about this sort of care across the continuum of life-- both age limits on the less than 18 side, but also at the greater than 65-year-old side, where we see, often, eligibility criteria structured around a maximum age that don't often make a lot of sense.

So that is one of several topics that we are addressing. As you know, we have a variety of networks and programs, and we fund a variety of kinds of trials. Some are led predominantly by the academic institution. Some are led through NCI networks. And so we are rolling out these policies, not in a one shot fits all way, but across these networks at different scales. They often require scientific buy-in from the other participants, and you know how that process works.

I think this is an area, fortunately, where there is a lot of buy-in, where we're not having lengthy debates about whether or not we should do this. Really, the question is how we operationalize it and make it happen as quickly as possible.

Dr. Clifford A. Hudis: That's great. And you know how strongly supportive we are, on lots of levels, for this effort and the related ones, in terms of barriers to accrual. I want to pivot, though, back to something that you introduced earlier about the big data. And my understanding is, in the annual plan and your bypass budget for 2020, you specifically called out the need to harness big data to speed up all of our work across the cancer research enterprise.

And there are many companies, organizations-- we ourselves at ASCO have CancerLinQ-- that are involved in trying to collect data, share it, analyze it, and advance science and clinical care. But what exactly do you see as the NCI's role in facilitating this, and what do you think is our biggest challenge going forward?

Dr. Ned Sharpless: Yeah, it's an interesting topic. I think the-- it's maybe two things to say off the top about big data in cancer research. The first is the NCI already has one very important example of how big data can transform a field, and that's The Cancer Genome Atlas, which later became the Genomic Data Commons. This is petabytes of genomic data that we make available in the cloud now to any researcher, basically, who is interested in cancer.

And that set of data has led to thousands of papers and just a fundamental reorganization of how we think about cancer biology in many ways. And it's been a huge success, I would argue, and well worth the investment of the NCI to do it. And the data has been used in ways we never envisioned. We never thought of some of the papers and applications that would come out of the analysis of the Cancer Genome Atlas, for example.

But the problem, then, one quickly sees, is that while that data set is great, it's limited. It doesn't have the clinical data, it doesn't have radiology and histology, it doesn't have-- we don't really have a way of binning big epidemiologic cohort data, for example. So the GDC, the TCGA, the Genomic Data Commons, proves how useful these kinds of data aggregation efforts can be, but also makes very clear what the shortcomings of our modern efforts are.

The second thing to say is that this is a problem where the NCI is well-poised to be a leader, right? There are a number of issues around data sharing and data aggregation that really benefit from a Switzerland-like federal entity, a non-conflicted, dispassionate entity like the NCI that just wants to create the data structure in a way that's maximally beneficial for everyone, so that there are-- this is an area where the imprimatur of the federal government really allows us to play a role that would be hard for other groups to take on directly. And so I think this is a reason why so many groups have been looking to the NCI for leadership on this topic.

So what are the challenges to big data? Well, I think that one challenge that has been spoken about a lot publicly is this issue of data hoarding by scientists and physicians and people who have these sets of data they don't want to share for academic competitive reasons. That is a problem. I'm not going to say that doesn't exist. But I don't actually think that's the biggest problem.

I think a bigger problem around data sharing is just it turns out to be really hard to do. And by hard, I mean expensive. It turns out to be-- these various data sets were not created, initially, with the intent of sharing them. They're often in different formats. They're often governed by different kinds of data use agreements, which are governed by the consent form that the patient signed to have their data included.

And so linking them can be both very technically difficult, from just a computer science point of view, and can also provide a lot of administrative and logistical hassles from the data sharing, data use agreement point of view. And so each one of these things is just something the NCI has got to work through, or someone like the NCI-- is figuring out how to link disparate data sets, how to get the right kind of data abstracted from charts that we want, how to develop the right work force to study big data with big data analytics, and then that is a big problem.

So there are a number of areas where the NCI can address the challenges. And I think we'll make progress. I mean, the good news is that we understand these problems. This is not like we need to-- there's some fundamental problem of biology that we need to figure out. The bad news is that the problems are weedy, complex, and many, many layered, and require us working through them.

But that's what we can do. We have support from the government for this. The moonshot had a lot of funding for data initiatives, which we've been employing to get these structures going. And now the Childhood Cancer Data Initiative, for example, I think could really-- that's a nice demonstration project, if you will, because it's the right size. Childhood cancer is about 16,000 cases a year.

And so I think we can show what this radical data sharing, if you will, this data liberation project can do-- you know, that population and how useful it could be to larger groups of patients like lung cancer, breast cancer, things like that. So I think that these are the kinds of things the NCI can do with help from other federal agencies and academic partners and groups like ASCO.

This is certainly not an area where we plan to go it alone. There are a lot of stakeholders and a lot of great ideas. And I think that by organizing and convening these initiatives, we'll make progress.

Dr. Clifford A. Hudis: Well, I really, first of all, appreciate your calling out the fact that data hoarding in isolation is not the single biggest problem, because I think that's a frequently-cited limit. And I agree with you that it's less of an issue than all of the other ones that you highlighted. In that regard, I understand that you just announced a new office. I think it's the Office of Data Sharing? Can you expand on or explain how that relates to these challenges and what it's going to, hopefully, accomplish for us?

Dr. Ned Sharpless: Sure. The Office of Data Sharing is something within our Center for Bioinformatics and Information Technology. It's getting stood up now. It's been around for about a year, even less than that. It has a new leader and a few FTs, and it has a number of jobs intended for it. I mean, there are a number of ways that we would like the Office of Data sharing to-- a number of problems that we think that the ODS can help serve with the external community in terms of data sharing, like these issues around consent and data privacy that I mentioned.

But right now, an intense focus of that office, because it's something we really need to solve, are related, really, to the issue of accepting data and allowing access to NCI data at present. So we have this complex structure whereby academic investigators can give data sets to the NCI. That's harder than it sounds, because we have to make sure the data are of good quality and they're properly consented, and we understand the data usage agreements and that kind of stuff. And then we have a means to allow access to those data to accredentialed investigators. And there are a bunch of issues with that that are more complicated than you and I would want to go into right now.

But I think that's consuming a lot of the bandwidth at that office right now, is the problems around, for example, the dbGaP entity, whereby different investigators give data to the NCI and the rest of the NIH. That has caused a bit of a bottleneck, and so we're trying to work through some of those issues.

One thing, for example, that I think the ODS can do and is doing already is this sort of concierge-like function. For people who have large, valuable data sets that they'd like to give to the NCI, we should be able to take those data sets as quickly as possible. But something that's happened in the transmission of those data is that we've realized the quality isn't quite what we wanted or the format isn't exactly right, and so we have these questions, and they go back to the investigator. And there's this sort of cyclical loop that can take months and really substantially delay the process.

And so the ODS is jumping in there early on and intervening on that loop and making sure the data are the right format and the right quality at the time of initial submission, so that we don't have this back and forth that wastes a lot of time. So I think those data access and data transmission issues are a prime focus for the office right now, although it has a much larger mission as it gets stood up.

Dr. Clifford A. Hudis: Yeah, a little bit like CENTRA that Rich Schilsky runs for us here at ASCO, in terms of access. But at any rate, I want to take the remaining time we have, and maybe this is a speed round on the cancer research workforce. So a couple of quick questions, perhaps-- first of all, has the Cancer Moonshot Initiative had an impact directly on the kinds of awards that you're making available to researchers? And if so, how do you think that might evolve in the next couple of years?

Dr. Ned Sharpless: I think the moonshot, as you know, was intended to focus on these 10 areas identified by a blue-ribbon panel that were thought to be ripe for clinical translation, just about ready to go into clinic and to benefit patients in a very direct, immediate way. So the moonshot per se didn't include funds for things like really hardcore basic science or training, although certainly moonshot moneys are being used to some extent in both those areas, as necessary, as part of these translational efforts.

So I think that what the moonshot has done-- it's done a couple of things. So first of all, that most of the awards granted by the moonshot mechanisms are more these-- are not the traditional R01, but are more of these consortia and network grants. And I think we've built a lot of infrastructure for research efforts, say, in immuno-oncology or in pediatric cancer or in survivorship. And those networks will both-- well, they will live on beyond the moonshot in some cases, I'm sure.

And those networks will provide integrated research efforts, but also some training opportunities. So most of those include junior scientists and junior clinical investigators, and so there will be some opportunity for the moonshot both to drive the scientific area of study and also provide some training opportunity for the new people coming up.

Dr. Clifford A. Hudis: Well, speaking of junior and new, I listened to your conference call, I guess, about a week or two ago talking about the pay line. Can you expand on your plans to support young investigators right now, given the always-present constraints in funding?

Dr. Ned Sharpless: Right. This is a particular problem for the National Cancer Institute, because we've seen this relatively-- there's no other word than "massive" influx in the number of applications for the so-called R01 grants, the independent investigator-initiated award at the NCI. And this is-- our award number is something up like 60% over the last nine years or so.

So this rapid increase-- which is, in most ways, a very good thing. I mean, that says that new scientists are coming to our field with new ideas and new ways to treat cancer, and the NCI can pick among these many applications and fund the very best ones. But it has this pernicious bad effect for the academic investigator community, and that is that their individual chances of getting a grant are lower.

If paylines are really the number of funded awards divided by the number of applications, and the denominator goes up faster than the numerator-- both are going up, but the denominator goes up faster-- then the paylines are going to go down. And we think this is particularly a problem for junior scientists, because established scientists have seen paylines come and go and funding realities change.

But new scientists aren't as used to the life of the independent researcher and, we think, are most likely to either leave science or move out of cancer research to another area of science. And we'll have to try and minimize that from happening, to the extent possible. So one of the things we've done at the behest, in fact, of 21st Century Cures, which included language asking the NCI in the United States to do this, was really focused on these so-called early stage investigator, the ESI.

So the ESI is faculty. That's someone who's gotten a job, generally in an academic institution, and is now writing their first R01 grant, their first independent scientist grant. And we've done a few things for this population. One thing that's really important is we give them a special payline. We give them, effectively, a higher chance of getting funding.

So if, say, paylines are on the order of 8% now for all Comer grants, for ESIs they'll be more like 14%, right? So a significant-- or 12%, in that range. So, significantly higher than what the general community is. I want to point out, also, that paylines are lower than the actual success rates of the NCI, which is a better number. The reason success rates are higher is because we do fund a lot of grants outside of the score. It's a little bit of inside baseball. But generally, if you write a grant to the NCI, your chance of getting it is more like 12%. And if you're an early stage investigator, it's more like 16%.

Dr. Clifford A. Hudis: Thanks, Ned. To switch gears a bit, I know you've worked with the NCI throughout your career. But now you've been at the Institute's helm for nearly a year and a half. Has your understanding of the NCI and its role in cancer research changed or evolved in this newest assignment?

Dr. Ned Sharpless: I think it has to be said that I was an NCI watcher my entire research career, and I thought I knew the National Cancer Institute and the National Institutes of Health pretty well-- as well as one can know these organizations from the external perspective. But since starting at the NCI, I've really learned that this amazing organization is much larger than even I realized, and that the scale and scope of the NCI is truly both awe-inspiring and, in some ways, daunting.

I had a series of meetings as I started as NCI director where I would learn about these sprawling comprehensive cancer prevention and control efforts or new areas of basic research or clinical trials. And I just really had had no idea that the NCI was involved in some of these activities. So it was very illuminating.

In some ways, it's thrilling, the things the NCI is doing. But I think it also made very clear to me another thing that I think I knew at some level, but didn't really appreciate the full scale of this until becoming NCI director, and that's the issue of-- although the NCI is huge and has this great reach and comprehensive nature, we are limited in scale. Our resources are finite, and the NCI, therefore, is really forced to make these difficult choices about which areas of cancer research to fund and how best to address our mission of reducing cancer suffering.

So I think I was surprised both by the scale and scope of the NCI, but also by the fact that, despite how big the NCI is, it still has significant limitations on what it's able to do and has to make these difficult choices.

Dr. Clifford A. Hudis: ASCO recently launched the "I lived to conquer cancer" awareness campaign that spotlights federally-funded cancer researchers and the patients who inspire them. I want to close out our conversation today by asking you, why do you live to conquer cancer?

Dr. Ned Sharpless: Yeah, I think like just about everybody in the United States, my life has been personally touched by cancer. I've had friends and family members get cancer, and my father even died from cancer. Both of my sisters are cancer survivors. So I think I have a real personal stake-- like everyone in the United States, almost-- in seeing the reduction of cancer suffering and conquering cancer, if you will.

I also find the problem fascinating from an academic point of view. I was drawn to cancer research because I found the biological questions of cancer research so fascinating. So I live to conquer cancer from this intellectual point of view, as well.

And lastly, I have the experience of being a doctor, of being a medical oncologist taking care of patients with cancer. And I've had the frustrating experience of having patients not do well who I thought, I wish we could have done more for-- as well as the experience of taking someone who has a pretty terrible cancer but yet driving it into remission with therapy and then watching that person effectively survive the disease and become cured of it over years. And that is so special and so thrilling to be a part of that as a physician.

So I live to cure cancer because it's personally touched my life, because I am a scientist who is fascinated by the biology of cancer, and as a doctor I've had the experience of helping people survive their cancer. And once you do that once, you just want to do that over and over again.

Dr. Clifford A. Hudis: That's really great, Ned. It's fascinating to hear why progress against cancer is personally so important to you. And I'm sure all of our listeners enjoy hearing that, as well. I want to thank you again for joining me for this ASCO in Action podcast and for all the work you do at the NCI and across the entire cancer care community.

Well, thank you for having me. As you know, one of NCI's most important partners in this effort against cancer is really ASCO. And so it's great to speak to you today. And thanks for all the things that you guys do for patients with cancer.

Again, thanks to all of you for listening today. Those of you who want to follow Dr. Sharpless on Twitter, he's @NCIDirector. And you can always follow me @CliffordHudis, as well as ASCO @cancer. If you do that, you can stay connected to our work, of course, on social media. You can also go to the NCI's website, which is NCI.gov. With that, again, I want to thank Dr. Sharpless for joining me today. And thanks to all of you for tuning in.

Mar 06 2019
30 mins
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ASCO Chief Medical Officer Highlights Top Clinical Advances and Nine Research Priorities to Accelerate Progress in New Podcast

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Welcome to this ASCO in Action podcast. This is ASCO's podcast series where we explore policy and practice issues that can impact oncologists, the entire cancer care delivery team, and those individuals we care for, people with cancer. My name is Clifford Hudis, and I'm the CEO of the American Society of Clinical Oncology.

I serve as the host of the ASCO in Action podcast series. And today, I am really pleased to have as my guest Dr. Richard Schilsky. He is ASCO's senior vice president. And chief medical officer, and Rich is here to talk about our new clinical cancer advances report, which was just released. In clinical cancer advances, ASCO identifies the most important clinical research advances of the past year across the full range of cancers, and from prevention to screening to treatment and survivorship.

The report also announces what ASCO has identified as our advance of the year. And for the first time in this year's report, we will debut what we believe are the research priorities with greatest potential to advance progress against cancer. Rich, welcome and thank you for joining me today.

Thanks, Cliff. Great to be back.

now let's start with what we always do. Every year, we announced the advance of the year, the one area of clinical cancer research that has demonstrated the most significant progress in a year's time. And we've seen tremendous progress in the treatment of rare cancers, earning it the 2019 advance of the year recognition. Rich, can you talk about why this area was chosen? Why is this particular line of research so important for individuals with cancer?

Well, first, let me start with a definition of what we mean by rare cancers. And generally, what we're talking about are cancers that are diagnosed with a frequency of less than six cases per 100,000 cancer diagnoses each year. Collectively, though, because there are many kinds of rare cancers, overall rare cancers comprise about 20% of all new cancer diagnoses every year.

But those numbers may not even tell the full story, because as we learn more and more about the molecular subtyping of cancer, what we're learning, of course, is that there are many very, very rare mutations and fusions and other genomic alterations that occur in a very small proportion of even common cancer diagnoses. So the patient with lung cancer, who has a RET fusion that occurs in about 1% of all lung cancer cases, that begins to become a very rare subset, even though it's overall a common disease. So we're going to be dealing more and more with this general area of rare cancers. But the reason that it's so important to single this area out, of course, is because historically, we haven't been able to learn very much about these rare cancers, simply because they are rare. There aren't very many of them that occur each year. Therefore, they're difficult to study. It's difficult to complete clinical trials. It's difficult to find patient samples to be able to understand the underlying biology of these diseases.

And yet, many of them are refractory to standard treatments. Many of them have a very aggressive clinical course. And for patients who are affected by one of these rare cancers, they desperately need new treatments. And this year, we're seeing, for the first time, some real progress being made in a number of these rare cancers. I'll give you some specific examples that we called out in the report. So for example, although thyroid cancer is a very common form of cancer, anaplastic thyroid cancer represents only about 2% of all thyroid cancers. And of those anaplastic thyroid cancers, about 16%-- so now we're talking 16% of 2% have a BRAF mutation. But it's clear now that treatment with BRAF directed therapy produces a very high response rate in this rare group of individuals who have BRAF mutant anaplastic thyroid cancer.

Another example, take the drug we're all familiar with, trastuzumab. We know now, of course, that trastuzumab is effective not only in breast cancer, but also in gastroesophageal adenocarcinoma that's HER2 amplified. And there's emerging data that HER2 directed therapy may be active in other tumor types, where the HER2 gene is amplified. And one of those is uterine serous carcinoma. So uterine serous carcinoma is a rare subtype of endometrial cancer. And about 20% or 30% of those patients have a HER2 amplified gene driving their tumor. And trastuzumab has been shown to be an effective therapy in those patients as well. Last example I'll give you right now. A tumor that most oncologists probably will never confront in their practice, tenosynovial giant cell tumor. This is a very rare soft tissue tumor that occurs in the joints, typically of young adults, typically is refractory to all standard known cancer treatments. And yet, this year, we saw very promising results reported for a new class of anticancer drug, a CSF 1 inhibitor, called pexidartinib, that produced a 40% objective response rate in patients with these advanced tumors, compared to a placebo treated control group.

So we're starting to make real progress in treating these rare cancers, particularly when we can begin to understand their underlying biology, and develop a therapy that's directed at the key drivers.

It sounds to me-- I mean, in listening to that wonderful list of successes, that we've rolled up a process and an approach to drug development and science into a category that is appropriately called rare cancers. Because when you think about the way you presented it, which I think is lovely, first, rare cancers, as a group, aren't rare is what you said. Two, rare cancers cross from the rare histologies to include some of the common histologies.

But the underlying theme, if I think about the way we present this, is a deeper understanding of the driver mutations, allowing us to move a little bit off of histology towards genomics to define these diseases. And that's not to say that genomics is the only way we're going to make progress. But the unifying theme in these cancers is probably that shared trait of an alteration and a driver mutation and an available drug. And that's the advance that's helping us with rare cancers. Is that a fair roll up of that?

I think that is very fair. And you can think about it in terms of a common histology, like lung adenocarcinoma, having a large number of rare genomic subtypes, each of which comprises a rare cancer, if you will. Alternatively, you could think about it as in the trastuzumab example, of saying, well, if you look at the universe of HER2 driven tumors, those HER2 driven tumors comprise a whole bunch of different histologies. But they all are responsive to HER2 directed therapy.

And so you know, as we understand the underlying biology of cancer much more clearly, it's moving us away from the long held view that the way you diagnose cancer is looking under the microscope. And if you see something that you see only very rarely, you say it's a rare cancer, to we're not going to interrogate the cancer if we see a rare genomic alteration that occurs infrequently in the population of cancer patients. That's what we're going to call a rare cancer.

Yeah, I just say think it's almost like an introduction or a preview of an interesting future where more and more of the cancers we treat may be selected on this basis, rather than their conventional light microscopy appearance, right?

To be sure. I mean, we know still that context is important. Not all of these molecular drivers behave in the same way in every tumor type. We already have examples where not all the targeted therapies work equally well against the same alteration, again, in every tumor type. But slowly, but surely, I think the science is moving us toward a day where we will be identifying cancers, primarily, if not exclusively, by their genomic profile.

It may not be a single driver. It may be a signature. But that is ultimately is what we use to direct therapy.

So to some degree, this is a fulfillment of a multi-year view that we've had about where to invest in cancer research, and the fruits, I think, are obvious. But this wasn't the only advance that we reported on last year. It's the one we named as the advance of the year. But what were some of the other advances that we called out for recognition?

So as in the last several years, where we named some aspect of immunotherapy as the advance of the year, this year we continue to see progress in immunotherapy of cancer, particularly with extending the range of indications for many of the immune checkpoint inhibitor drugs, as well as new indications for CAR T cell therapies. So that continues to be a rapidly emerging area where there's a lot of progress continuing to be made. We continue to make progress how with the introduction of second and third generation targeted therapies.

We've come to understand, of course, that many targeted therapies although they work well for a period of time, cancers ultimately develop resistance, patients need additional treatment options after the first line of targeted therapy. And of course, the science has responded by giving us the insight as to the mechanisms of resistance, which has led to the development of second and third generation inhibitors that can effectively overcome the treatment resistance.

We're seeing this particularly in lung cancer, particularly with drugs recently introduced like osimertinib, which is effective against the T790M mutation, the common resistance mutation in EGFR mutated non small cell lung cancer. And interestingly, some of these drugs are also now showing much greater effectiveness in treating or even preventing the onset of brain metastases in lung cancers that commonly spread to the brain.

So this has opened up actually a whole new area of research on effectively treating and preventing brain metastases in those tumor types, where there's a high propensity for such metastases to occur. The last thing I'll mention as another area of continuing progress is the continuing development of new biomarker strategies to help us refine the way in which we select patients to receive treatment. And certainly, this last year, the big news were the results of the so-called TLRX trial in breast cancer, a test, a gene expression profiling test, that clearly indicates that there is a substantial proportion of women with hormone receptor positive early stage breast cancer who can safely forego treatment with adjuvant chemotherapy with no detrimental effect.

And this type of test I think is now going to really move us even further down the road of precision medicine, because it's allowing us to identify those patients who are most likely to benefit from adjuvant chemotherapy. They should get treated, and they will certainly benefit. But it also is allowing us to identify those patients for whom adjuvant chemotherapy is unnecessary, and who can be spared both the physical toxicity and the financial toxicity of adjuvant treatment.

The more of those tests that we can develop, going forward, the better we'll be able to refine prognosis, the better we'll be able to apply adjuvant therapy in the future.

I think one of the subtleties here is this highlights something we almost touched on before, which is precision medicine doesn't have to be only about gene rearrangements. There are multiple paths towards some degree of precision in treatment selection for individual patients. And this is, I think, a good example of that. It also is a good example of the fact that precision medicine is not actually just about treatment selection. It's about risk assessment, risk stratification, assessment of prognosis, identifying early recurrence, as well as directing patients to the right therapy at the right time, based on the biological characteristics of their cancer. So one of the things that we've done this year, and it's a first for us, is to announce a set of research priorities. These represent areas that our leading volunteers and others have identified as needing urgent attention. They are areas where the progress is promising, but not fulfilled completely. Can you talk a little bit about the motivation for creating this kind of a research agenda, as well as a criteria for actually selecting the specific research priorities? So obviously, you know, our field is advancing very rapidly. But there are still very many unmet medical needs. There are many clinical conundrums that oncologists face every day in practice. And we felt that given all the potential directions that research could take, ASCO is in a strong position to be able to at least begin to describe those areas, where we thought the potential benefits in patient care would be greatest, and could be realized soonest. ASCO, because we are the physicians who treat patients with cancer, we have a pretty good sense as to what the unmet medical needs of our patients are, what the lack of evidence is that our doctors struggle with every day in making clinical decisions with patients, where the field needs to continue to grow and to develop new information, to help fill those evidence gaps.

So we felt that we could take a stab at setting a research agenda, and putting out there where we thought the unmet needs, where we thought the opportunities were ripe for investment in research, and trying to articulate how, if we were successful in fulfilling those research needs and priorities, the field would ultimately be transformed. So that's what we've done with the nine research priorities that we are offering this year.

So the nine priorities that's important for readers in a moment, if they go look at this or pick up our publication to recognize, they're not rank ordered. They just happen to be nine. Maybe next year, there'll be fewer or more. And the second thing is in no particular order, as I understand it, we've divided them into a couple or maybe three big buckets.

One is essentially the issue of who really benefits from IO, the advance that you already talked about, as a multi-year call out from us. The second is really a little bit about health care disparities and precision medicine all rolled up in the concept of special populations. And related to that is access to research itself.

And then the third is something which we always worry about, but have, I think struggled with as a field for decades, and that is reducing cancer risk, along with screening, which is surprisingly still controversial in many settings. We'll talk a little bit more about some of the specifics, but I would just remind everybody listening that you can find a list of these nine research priorities if you go to our website asco.org/cca.

So Rich, as you think about the nine areas that are rolled up in those three broad areas, can you talk a little bit about how specific research would potentially transform patient care? And you've set a relatively short timeline for results in introducing this. And what kind of resources might these projects need?

If you take the first area, for example, of essentially getting the right treatment to the right patient at the right time, you know, we've touched on some of these themes already. Look at the results so far with immune therapy for cancer. It's remarkable that a significant, although still small fraction of patients across multiple tumor types, who receive an immune checkpoint inhibitor, will have prolonged disease control, 20% or so of patients apparently surviving, without disease progression, or even disease free for many, many years in melanoma and diseases that previously were death sentences for patients.

The question is why is it only 20%, and who are they? Because these drugs are toxic. They're expensive. And what we'd like to be able to understand is, what are the characteristics of the tumor or of the host or of the treatment that makes the treatment so effective in a proportion of patients, so that we can then learn how to increase its effectiveness in those groups of individuals, where it has so far been less effective.

The same is true, as we touched on a moment ago, regarding adjuvant post-operative therapy. If you think about solid tumors, broadly speaking, roughly 50% of patients with a newly diagnosed solid tumor are cured by surgery alone. They don't need and can't benefit from adjuvant therapy. Of the remaining group, who are at higher risk of recurrence. Many of them will not benefit from whatever adjuvant therapy they might receive. So what we observe in most clinical trials of adjuvant therapies are relatively small absolute improvements in say disease free and overall survival for the entire population of patients treated. But of course, what that likely represents is a substantial benefit for a small proportion of that population. So what we are suggesting in this research priority is additional research, similar to what we saw presented this year with the TAILORx study, that allows us to understand the biology, the biomarkers, the testing that can be done to identify the patients most likely in need of and those who will most likely benefit from adjuvant therapy.

And then the third area within this general theme goes back to immunotherapy and the enormous promise of CAR T cells, which so far, has been realized almost exclusively in patients with hematological malignancies. So that's wonderful. And we want to extend that benefit as far as it will go.

But the question is, can those treatments be effective in solid tumors, which generally have a much more complex biology than many human hematological malignancies, and how do we develop CAR T cell therapies that can be effective in the solid tumor setting, that can be delivered to a solid tumor patient population, and ideally, and this may still be a bit of a pipe dream, can we develop CAR T cell therapies then that can be developed and administered off the shelf, so that they don't have to be custom made for each individual patient, which drives up the complexity and the cost of treatment. So those are the key elements of this initial theme.

And in a similar way, we would have similar, or we would have short term plans for the other areas that we haven't gone into detail here. And again, I would remind listeners that they can go through our whole list of ideas in terms of areas of focus at asco.org/cca. Right?

Absolutely. And when they do that, what they'll find are that we are calling for increased research in precision medicine and pediatric cancer. We're calling for increased research that's necessary to optimize the care of older adults with cancer. We're calling for research on how to ensure more equitable access to cancer clinical trials, so that all patients can benefit from those studies, and we can make progress more quickly.

And then finally, of course, we're very interested in learning more about how to reduce the long term consequences of cancer treatment. The pediatric oncologists have actually been quite successful at this, because first of all, they've been very successful at curing children. And now, they've been able to show that they can begin to pull back on certain components of therapy in a very thoughtful and well studied way, so as to not diminish the chance of cure, but to diminish the risk of long term side effects of treatment. We, of course, want to have more research done, addressing the challenge of obesity in this country and its link to cancer risk, cancer progression, and cancer treatment, and then finally, to identify strategies to better understand the biology of so-called pre-malignant lesions, so that we can understand which pre-malignant cancers are the ones that are destined, in fact, to become invasive cancer.

That latter touches on a theme we could talk about another day which is the building, the emerging drive to rename some of those cancers, as something less than cancer, because of their lack of at least acute life threatening potential, right?

We could talk about that another day, and we should. Yes. So one of the things that I think is always important to point out is we can do all of this work, but of course, we are part of society, and we're dependent upon various sources of funding and other resources in terms of public policy. We are dependent on government ultimately for support, as well as private support. And I think this clinical cancer advances report highlights that there are policies that would help us improve and accelerate clinical cancer research.

Some of them are obvious. We talk about them in other podcasts, increasing access to clinical trials, covering the routine quest of care for trial participants, and indeed, increasing overall federal funding, not in an unpredictable way, but in a steady way, that allows us to make multi-year plans across our community. Given all of that, what steps do you think ASCO members, specifically, could take to support us? And I would take it a step further. What should they be telling their representatives in Congress in terms of these policies? What should they be telling them in terms of supporting these critical areas of cancer research and how can they make an impact? It's clear that essentially all progress that we make in developing new treatments for cancer ultimately gets linked back to federally funded support for basic science research. All of the insights that we've developed in terms of what causes cancer, how it progresses, which are the high risk populations, so much of that information comes from data sets and other basic laboratory studies, funded by the NIH or the National Cancer Institute.

Of course, the NCI has in place a robust national clinical trials network publicly funded that supports clinical trials that would never be done by a commercial sponsor. In fact, three of the rare cancer studies that I mentioned earlier during this podcast were done with support from federal funding.

Those studies, because they are rare cancer, small populations are not studying tumors that represent a large market for a new pharmaceutical product. They're not going to be done by a commercial sponsor. We need federal support. And we need our members to point out these kinds of examples when they go to talk to their representatives in Congress. And I would urge our members to not only go to talk to your representative, but to bring a patient with you.

The patient tells a story far better than we can. And having the patient at your side and having the patient tell their own story about how they benefited from federally funded research is very powerful. In order to reach your member of Congress, ASCO's trying to make that as easy as possible, and you can do that by going to ASCO's Act network at asco.org/actnetwork. That's great. I mean, we've covered a lot of exciting progress, I think, this year. And readers who take the time can dive far more deeply into this discussion with our publication. But what would you say is the main takeaway, the thematic takeaway that you hope people will get from this year's clinical cancer advances report? To me, I think what we continue to see this year, and we have seen in recent years is that the more deeply we understand cancer biology, the more that will quickly lead us to new therapeutic approaches that will be far more effective, and hopefully, less toxic, and maybe most importantly, more enduring than the common therapies that we've had available to us in the past.

Our field is clearly moving to a day when immunotherapy will be central to cancer care, when every patient will have their cancer genotype well understood, and where therapy decisions will be informed by that deeper understanding of each patient's biology. So you almost did this, but I'm going to push you a little more. In the same way that we're now calling for what should be done next in terms of research, if you could actually look into the future, what areas of progress against cancer would you expect or maybe hope to see, just 12 months from now, when we do this report again? I hope that one of the things we'll see is rapid progress in developing, not necessarily novel biomarkers as unique tests, but novel biomarkers signatures. I think it's becoming increasingly clear that in order to select patients optimally to receive immunotherapy, and even to select patients to receive certain precision medicines, that a single biomarker is not necessarily the optimal selection strategy.

For immunotherapy, we may need to see a signature that represents some characteristics of the tumor, some characteristics of the patient, maybe even some characteristics of that patient's microbiome in order to figure out who is most likely to be susceptible to which immunotherapy approach, and the same is going to be true, I think, for even the now common precision medicine approaches with small molecules. We're trying to understand how molecular pathways and networks work inside the cell can suggest to us not which single targeted therapy to use, but which combination of targeted therapies to use for each individual person.

This kind of work is on the horizon. It's complicated, involves lots of complex algorithms. But my hope is that this will move us to a future where we can take the results of a test on a patient's tumor and integrate information of various sorts and come out with a more precise estimate of what's likely to be the best treatment for that person. And you think that we could see some of those results even as soon as just 12 months from now, or is this a longer term hope? I think we will begin to see some of these types of approaches appearing at an ASCO meeting in 2020.

Well, that's really exciting. I think it's really both uplifting, and I think challenging to hear where we are, because of course, as is always true in science, every answer begets many more questions. And in our world, every bit of progress identifies new challenges. And I think that's what's summed up in a lot of what's in this report now, right?

Absolutely. But you know, I think for the first time, you know, ASCO is trying to articulate where we see the greatest opportunity. And we hope to be able to do this each year in the coming years. As you said earlier, it may not always be nine research priorities. Some of that might even be repeated year to year, because we won't solve every one of these in a year from now.

But we will modify these. We will improve upon them, and they will change as the science advances, as the questions evolve, and as the opportunities continue to develop.

Well, rich I want to thank you for joining me today for this ASCO in Action podcast. I'll remind everybody, we have a mission at ASCO to conquer cancer through research, education, and promotion of the highest quality cancer care. And this clinical cancer advances report really does help us meet that mission, by increasing awareness of the progress we're making, but also, as you point out, identifying the critical importance of the entire community's engagement in research and high quality care. That is pointing out just how important all that is in terms of delivering on the promise of all of our progress.

I encourage listeners, again, to read the full report by visiting asco.org/cca. And until next time, I thank everyone for listening to this ASCO in Action podcast.

Feb 12 2019
32 mins
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Exclusive Interview: FDA Commissioner Talks Drug Pricing, Expanded Access, and Tobacco

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"Welcome to this ASCO In Action podcast. This is ASCO's monthly podcast series where we explore policy and practice issues that impact oncologists, the entire cancer care delivery team, and the individuals we take care of, people with cancer. My name is Clifford Hudis, and I am the CEO of ASCO as well as the host of the ASCO In Action podcast series. For today's podcast, I am delighted to have as my guest Dr. Scott Gottlieb, the commissioner of the United States Food and Drug Administration.

The FDA of course plays a critical role in the delivery of high quality cancer care by reviewing and approving cancer treatments. This continues to generate discussions about the pace of scientific advances, and indeed the regulatory role of the FDA. Given that, we are really lucky to be able to talk today with Dr. Gottlieb about the FDA's efforts to increase overall efficiency by updating or modernizing aspects of our clinical trials conduct and expediting the end to end drug development process.

I will admit that I'm going to take advantage of this opportunity to also ask how his agency is tackling the issue of tobacco control for the next generation of tobacco products, another area of deep concern from our community and others. Dr. Gottlieb, welcome and thank you for joining me today.

Thanks for having me here.

Great. Now as a professional society, we are very focused on the intersection of science and society. Given that, and noting that you've been at the FDA for more than a year following a long career in public service and in private industry, I have to start by asking, for you, has your current experience changed or evolved your view of the FDA's role or functions, and if so, how.

I've been at the agency three previous times. I had a good sense of what the agency's public health mandate was and what its mission was. I think that the nature of the market and the science that we're grappling with has certainly forced or compelled the agency's mandate to evolve. I think what we're seeing right now is, I feel like we're at the inflection point with respect to a lot of new opportunities from technology.

We look at things like gene therapy and cell-based regenerative medicine. Those fields largely didn't exist last time I was at the agency, and now we're an inflection point where we're going to see gene therapies approved to the market, and we saw three CAR-T's approved already, that are going to fundamentally transform the treatment of disease.

When I was last here, we were talking about the ability to advance genomically derived drugs and have more targeted approach to the treatment of patients where you can get the right drug to the right patient at the right time with sort of a drug diagnostic system, yet seeing some early examples of that. But now that is a much more routine development pathway.

With respect even to tobacco, you mentioned tobacco at the beginning, we're at a point right now where we have the opportunity to use new technology potentially to help currently addicted adult smokers transition away from combustible tobacco products onto products that we presume don't have all the same risks associated with them.

And so using new authorities we have to regulate tobacco, including regulate nicotine levels in combustible cigarettes to render them minimally and not addictive, and allowing for a regulatory pathway that puts some of the new technologies like e-cigarettes through an appropriate series of regulatory gates, we have the opportunity to transition adult smokers off of combustible tobacco with all their morbidity and mortality associated with combustible tobacco use more rapidly than we did in the past.

And so across the board, I think we're seeing technological inflection points. Digital health tools are another example that are not only creating significant new opportunities, but I think compelling the agency to rethink its traditional approach to regulation in order to accommodate the opportunities that these new technology platforms create.

So is it fair to sum all that up as, the agency is recognizing that technology in many domains is defining and driving the need for new regulatory frameworks, and in turn, we have to educate Congress and others to make sure that the agency actually has the appropriate authorities. Is that the virtuous cycle you're describing, you think?

I think that's exactly right. I think that there are areas of profound technological change where the traditional approach to regulation doesn't apply well. Digital health tools, probably a very obvious example where you can have sort of practical incentives, where you have a digital health tool, you might evolve it almost on a daily if not weekly basis in the marketplace. It's a medical product that's a digital health tool, like a medical lab, for example.

And a regulatory process that requires you to come in and file for premarket approval every time you want to make a modification or have to file a 510(k) supplement, that is antithetical to the rapid cycle of innovation and evolution that those kinds of products undergo.

So we had to think of a new regulatory paradigm for how we would treat these products, and that's where we move towards the Pre-Cert model, where effectively what we're doing is validating the underlying architecture of the platform, of the software platform, and validating the SOPs, how good is the company at certifying its own software and validating its own software products, and then we would allow them after an initial approval to come to market with modifications as well as subsequent approvals without having to seek premarket clearance from the FDA every time.

And we would shift toward the postmarket regulatory regime for subsequent products. So basically, instead of regulating the individual products, in essence we're regulating the firm and taking a firm based approach. That's an example of where we've had to rethink our regulatory model in order to accommodate a much different approach to innovation.

Another example is with cell-based regenerative medicine, where we have very clearly said that we think that there's a lot of opportunity with cell-based regenerative medicine, but we also see a lot of clinics promulgating products based on what we think is incomplete if not poor science and creating substantial risk of patients using cell-based products intrathecally, or for injections into the eye, where they're creating substantial risk and don't have really a scientific basis to argue that there's convincing evidence of a benefit.

And these products are clearly subject to FDA regulation. They cross the line between what is and isn't regulated by FDA, but subject to enforcement discretion of the agency over many, many years. Prior to when I came in here, the agency didn't actively regulate these products. We have said very clearly, we're going to actively step in to regulate this field. In fact, it's going to take a number of enforcement actions, and we'll be taking others. At the same time, we also recognize that a lot of these technologies are being promulgated by small developers, and there's a lot of promise here. And so we've had to again come up with a more accommodative approach. But how do we regulate a field where a lot of the really interesting innovations are being brought forward, for example, by academic investigators working in small clinics. And so what we've said in that case is that we'll allow investigators to pool their data so long as they follow common manufacturing protocols that are doing similar things with cells. And it can file a common BLA, common Biologics License Application. And then we'll give individual licenses to the individual institutions or individual investigators. That's a much different approach to regulation than what we've traditionally done where you think of, we regulate companies, we regulate a biotech or a pharmaceutical company. We had to ask ourselves, how do we regulate small clinics or even institutions, academic investigators in institutions, who want to promulgate these technologies. And we've come up with an approach to do that.

So at the same time that we've said we're going to be taking more enforcement action to make sure patients aren't being put under duress, we're also going to take a more accommodative approach to allow for regulatory approval for products that are being, in many cases, promulgated by smaller entities and individuals.

So that actually lets us pivot, I think, to an area of traditional focus for at least a large group of our members at ASCO. And that would be drug development. And it's clear that you've made it a priority to streamline how new drugs specifically are reviewed and approved. And I think as part of that effort, recently you announced a new office. It's the office of Drug Evaluation Science. And my understanding is the goal is to centralize performance metrics like biomarkers, patient reported outcomes. How do you see this new office specifically helping to support this goal of a more standardized and ultimately more efficient and faster review process?

Well, the Office of Drug Development Science, the goal there is to create an infrastructure here that will help better validate scientific tools that are being used to help advance drug development, like patient reported outcomes, like bioinformatics. What we've seen is that these tools now, there's a lot of hard science behind these tools. And they've become much more commonly used in drug development programs.

And so we need an infrastructure here that not only provides for a more standardized approach to assessing these modalities when they're incorporated into applications, but also helping to advance the science of how to use these tools. I compare it to what happened in 2003 with modeling and simulation. And I was here during the time period.

What we were seeing over that time period was we were seeing more drug developers starting to use modeling and simulation as a component of their overall drug development programs. And we saw modeling being included in applications. Early on, it was often used for dose finding because you wanted to give the dose finding trials. But then you wanted to use the data that you derived from the dose finding trials to simulate what would happen if you picked a dose in between the two doses that you might have tested. And so we said to ourselves, well, this is very interesting. This could really help inform drug review better, give us more information about safety and benefit. We need some standard approach to how we're going to both evaluate these tools as well as help develop them into a harder science so it could be more rigorously used in drug development.

We created a Modeling and Simulation Office when I was here. Mark McClellan was involved in doing it. He helped recruit the guy who stood it up, him and Janet Woodcock. It was Larry Lesko. And it started as a two-man office.

Now, we've got probably 30 or 40 people in the Modeling and Simulation Group in Cedar. And well more than 95% of all applications that we get for new drugs contain a component of modeling and simulation. It's now a routine part of drug development. And we have a rigorous approach to evaluating these components of the applications as well as helping to evolve the field through multiple guidance documents that we've put out. I see the Drug Science Office, this new office that we created within the Office of New Drugs, working in a similar way where it's going to be a holding office, if you will, for new areas of science that can help improve tools used to inform us about the risks and benefits of new products.

So I want to pivot from that to one of the big societal issues. And you and I have been discussing this informally, I think, for more than a year-- drug price. The Trump administration has made it a priority to address the cost of drugs, price specifically. And I guess the question from many will be how confident can we be that ultimately a faster and more effective drug development process will itself actually and favorably impact the costs of drugs. What's your feeling about that, knowing everything that you're doing that's supportive in that way?

Well, I see my role in the drug price debate to be focused around creating product competition. You have price competition. But you can't price competition without product variety and product competition. And we're focused on creating the product competition by facilitating entry into the market of generic drugs, but also, facilitating a pathway that allows for follow on innovation within categories.

And what we've seen-- and we've analyzed this. We're going to be publishing this data soon. But what we've seen over time is that second to market innovation within a category is coming to market much more slowly. We looked at a cohort of approvals from the early 2000s. And then we looked at a more recent cohort of approvals over like a five-year period. And it's very clear that when you look at areas of unmet medical needs, orphan drugs, first in class drugs and oncologies, the second to market innovation is taking much longer to come to market and more categories of drugs are remaining sole source drugs in perpetuity. So to the extent that you're not getting that second to market innovation for new drugs, that is thwarting the opportunity for price competition within those categories. Because you do see price reductions. Oftentimes those price reductions come in the form of rebates that aren't transparent to the consumer. But there are price reductions or discounting nonetheless when you have a second and third to market drug within a category.

And the hepatitis C category was the best example of that. We saw a very dramatic price reductions in negotiations once you had multiple entrants in that category. So we're focused on that. And we're asking questions about why it's become harder to bring second to market innovation to patients. And I think that there are some very specific reasons and there's things we can do to help address that, to make it less costly to bring second to market innovation in an area of unmet medical need.

If the trials are onerous or very costly to bring that second to market drug to the market, sometimes the economic opportunity might not be robust enough after this one entrant, especially when you're talking about very narrow niche categories of unmet medical need, they're might not be enough economic opportunity to incentivize that second to market innovation.

I think where-- just to sort of close, I think where this might be most evident is in some of these inherited diseases. You've seen this play out in gene therapy, for example, where once you come to market with a treatment and you treat the prevalent population, the people who already have the disease, the incidence population, the number of people who are going to get it on an annualized basis, that might not be a big enough market to support a second entrant that's going to split the market with the first in class product. And so I am quite literally seeing investors pull out of these opportunities which we see what we think are applications being slowed down. We see people pull out if they think they're going to be third to market. And that's ultimately bad for patients. Because it's not just robbing patients of product competition, but it's also robbing them of potential product variety. And we know not every patient responds to a treatment the same way. So you want differentiation in the market.

And also if there's a horse race between being first, second, third to market and the third to market pulls out because they don't think they're going to be first or second, sometimes the first or second doesn't pan out. And then you're stuck with nothing. So this is not a healthy development. And if there's things we can do to make the development process more efficient to create more entrants, that's something we're focused on.

So that's great. You raised at least two issues that I want to pursue a little further. Let's start with the first one, which is technology based. Recently you announced specific plans to keep pace with the influx of applications for selling gene therapies. And you've referred to that already in your comments.

But you've raised concerns specifically around, I think, if I understand it, reimbursement environment for CAR-T therapies and a fear that that reimbursement challenge may, in fact, stifle innovation that's needed. Is there more to say about that? Or is that pretty much the issue right there?

Well, I think that that's one of the issues. I think the issue, obviously, is-- and many people who are in this space are acutely aware of this-- is that there's different pay structures on the inpatient and the outpatient side to the extent that some of these products are being labeled for use in inpatient only. The reimbursement on the inpatient side is much lower and more difficult than reimbursement on the outpatient side right now. So that's an unusual situation and something that's artificial. I mean, a drug shouldn't be reimbursed diametrically differently just because it's delivered in one setting versus another and the reason why you're pushing it into an inpatient setting is for safety considerations. And so I think it's something we need to address. We can't allow that sort of artificial differentiation to persist.

There's a lot of late stage CAR-T development. But we're not seeing a lot of early stage CAR-T development. And if you talk to people in the field, they'll say, well, it's because CAR-T hasn't demonstrated its ability to really potentially be effective in solid tumors. And a lot of the liquid tumor opportunities are already being pursued. I'm not sure that's true. I think that there is a reluctance. At least part of it is a reluctance to make significant investments right now because the reimbursement environment is so uncertain for these products. So that ultimately needs to be resolved by others, including CMS. But I think that there are things we can do as well here at FDA.

So for example, we say that a product should be labeled for inpatient use because we believe that with certain risks associated with the delivery of some of these products-- and you're very familiar with those risks and so are all your listeners-- require the ability to deliver intensive care or significant medical services if a patient does have a reaction on an infusion of this product. But that doesn't necessarily mean that you need to be in an inpatient facility. What it means is you need to have within a reasonable period of time-- and you can define that period of time-- access to significant supportive care. I know institutions where the inpatient infusion center is further away from the medical intensive care unit than the outpatient infusion center. So that makes no sense. Why would you say it has to be in an inpatient setting when the inpatient setting actually is further away from the kinds of medical resources that we want accessible to the patient?

So really what we should be considering is defining and labeling the kinds of services that need to be available within a certain period of time, and not necessarily inpatient or outpatient. Because there are a lot of outpatient infusion centers that are adjacent to academic institutions where you can have a significant amount of supportive care delivered very quickly. And the patient is very accessible to a medical intensive care unit if they do have an adverse reaction. So we're rethinking that, how we label these products. But that's a-- it might solve the proximate challenge. But ultimately, I think you need a fundamental solution to the pay structure so there's not an artificial divide between the inpatient and the outpatient with respect to these products.

So just in the interest of time, I want to make sure we cover the monetization of clinical trials because that's the other issue, I think, rightly raised. And you've for a while made this a priority, I know. And I'll just jump ahead and say, and I think if I remember correctly, your agency the FDA issued two draft guidance documents on innovative trial design within the last year. The first focused on master protocols. And the second on specific advice in terms of design and conduct for adaptive trial designs. That's a compressing approach in terms of the phases of traditional studies. Can you talk a little bit about why this is important and what kind of savings you think this could actually deliver as a practical matter?

I think it's important because, first of all, I think a lot of the drugs that are being put into development can't be developed efficiently with the traditional approaches to drug development. So for example, you think of a drug where it's targeting molecular change that's apparent in multiple disease states. This is most obvious in cancer where you have tissue agnostic approvals where you might want to do a basket trial where you test a drug in multiple tumor types where what's driving the tumor is the same genetic alteration, molecular change.

And you want to be able demonstrate that it works across multiple tumor types, especially with rare tumors where you might not-- if you said, well, you have to prove it first in lung cancer and then you go on and prove it in liver cancer. But it might be such a rare genetic change that you're not going to be able to efficiently enroll just in lung cancer and liver cancer. So you want to pool the data across multiple tumor types to demonstrate statistically significant evidence of benefit.

I think because more drugs are being designed that way, we have to rethink how we allow sponsors to conduct clinical trials, structured clinical trials. And so things like basket trials and master protocols and tissue agnostic approvals become very important in this paradigm.

It also can allow for a lot more efficiency. A master protocol can allow you to test multiple drugs within the context of the same trial. If you have a situation where you're looking at targeting a rare disease or a rare subpopulation of a disease, where it's hard to recruit people, if you have a master protocol set up, you can test multiple drugs in the same population much more efficiently. So as we develop drugs that are targeting smaller and smaller populations and delivering, in many cases, outsized benefit and demonstrating earlier evidence of benefit, we need to rethink how we structure trials to take advantage of those opportunities. I think one of the-- we approved a record number of novel drugs this year by a long margin, 59 approvals. The second best year, which was last year, in modern times, I think was 46. We approved 19 new NDA and BLA products focused on cancer and had 38 supplements this year.

If I was to point to one thing that's driving that innovation, it's the fact that more of the drugs, many more of the drugs that are being put into development now not only have a very plausible biologic rationale for why they're going to deliver benefits, but they're so well targeted, so the underlying disease state is so well understood, that we're seeing much more significant benefit much earlier in drug development in much more compelling disease situations. And so, proof of concept is established very early. And you can establish statistically significant evidence of benefit in a very small series. And that's accelerating these products through development. And more of these cases are situations where you're targeting such significant unmet medical needs that even if there is uncertainty around the full scope of the safety profile, the outsized benefit in that clinical setting overwhelms any of that uncertainty. And so you can move these products through development much more efficiently. That's the nature of the science that we're seeing right now. And I think it's going to be the way we see the field move forward, at least for the foreseeable future.

You know, one of the issues that this raises is the issue of targeting and niche subpopulations which you've referred to. We've tried to deal with this within ASCO by launching TAPUR, which takes next gen sequencing, by and large, and matches patients who are theoretically scientifically appropriate for off label use with drugs that are in the market but where the indication doesn't include their histology. And I know your agency is familiar with it.

But that, in turn, generates prospective evidence. The vast majority of patients, as you know, in the United States simply don't have the opportunity for various reasons to participate in clinical research. And that has raised questions about the utility of so-called real world evidence and real world data.

You know that the FDA has been working closely with ASCO, especially with our big data project CancerLinQ, so that your agency has access to our growing big data repository. And that in turn, we all hope, will inform certain aspects of regulatory review, I guess mostly in the area of label extensions.

So your agency recently released a framework providing detail on how the FDA is going to develop guidance for real world data in drug regulation. And we're especially excited by this. We're invested in this, in a sense. And we look forward to working on it as it rolls out.

How do you see this framework being implemented specifically? How is it going to benefit patients?

I think it's going to address one of the things you said right up at the top, which is patients don't have access to clinical trials. I think as we make more rigorous use of real world evidence in the development process and in the regulatory review process, that's hopefully going to open up the opportunity for data collection and clinical trials to move out into the community.

Real world evidence isn't just evidence collected after the fact. You can have real world evidence collected in randomized settings. You can have real world evidence collected in prospective settings where you have large, simple registries and other kinds of constructs. And so, as we're able to make more rigorous use of these kinds of data constructs, I think it's going to push clinical data collection further out into the community so more patients are going to be able to access experimental protocols where the evidence is being generated that's going to help inform regulatory review, either in the pre- or post-market setting.

And we're clearly making widespread use of real world evidence in post market setting, particularly for confirmatory studies post approval. And you're seeing situations where it's also informing decisions on the premarket side as well.

So I guess, since we're talking about access, one has to at least address the question of very ill patients and access to investigational drugs outside of the clinical trial system, what's been called expanded access. And this has been a topic of great discussion and debate for the last couple of years. Can you talk about some of the specific changes that the agency is making and how you see this helping patients and physicians navigate the new expanded access program?

Well, the one that we announced recently is that we're going to create a service here at FDA where we're going to staff it. Initially it's going to be sort of a pilot. And we'll focus it on oncology where we'll help patients navigate the expanded access process soup to nuts where effectively they will be able-- if someone identifies an expanded access protocol that they want to get entry into with their physician, their physician is going to be able to call FDA. And FDA is going to help guide them through the process, soup to nuts. FDA will have people who will make the outreach to the sponsor and do the interface with the patient and provider to make sure the documentation is done in a timely fashion.

This is also going to have the advantage of allowing us to be on the phone with the drug sponsor to understand why drug sponsors might not give access in certain settings. And so what we find is, in some cases, we're willing, we approve the ability for a patient to get access to a product, but the drug sponsor might turn it down. And so this is going to allow us to collect more information about why it might be turned down.

It's also going to allow us to identify situations where there might be a lot of requests of one drug company so that we can intervene to help encourage the development of a true expanded access protocol. If there's a lot of compassionate use requests, for example, of a single sponsor or a single drug, those are situations we might pick up the phone and say, hey, we're approving or we're getting requests for a lot of compassionate use. Why don't you think of starting an expanded access protocol? We can work with you on that.

So I think that having FDA be an interface there is not only going to make it more efficient for the patient and provider to access the system, but hopefully will also allow us to interface better with sponsors to sort of create the conditions where drugs can be made more widely available under appropriate conditions. And just for clarity, I assume that there is a 800 number or web URL for that. Is that right?

Well, we stand it up. It's still in process. So it's something that we're going to do soon. But yeah, this will be widely disseminated to folks.

Great. So the last thing I want to talk about, which brings us in some ways back to our roots, is tobacco. And I said at the top of this that we would touch on this. This is an area where our field saw slow but ultimately critical progress starting in the 1960s. And all of this feels like it might be jeopardized by a recent and alarming uptick in tobacco use in children, essentially kids and young adults. And this is just setting off, as I say, alarm bells across our field. I think there's data from the FDA and the CDC that in 2018, 3.6 million students were e-cigarette users. And this was compared to just 1.5 million about a year earlier.

Now there's still not a lot of research on Electronic Nicotine Delivery Systems or so-called ENDS. But there is at least some reason to believe that they might increase the likelihood of nonsmokers or former smokers converting to combustible tobacco with their known risks.

So last year, I know that the agency announced the Youth Tobacco Prevention Plan to address this alarming trend. And it'd be great if you could talk a little bit about the plan and what you intend to do and update it, as I know you've been talking at least on social media about this issue in particular.

Well, we think that the non-combustible products like e-cigarettes provide a potential opportunity for currently addicted adult smokers to transition off of combustible tobacco onto modified risk products. These products, the e-cigarettes, need to be put through an appropriate series of regulatory gates. But I've said many times, if we can transition every adult smoker off of cigarettes, traditional cigarettes, onto e-cigarettes, that's going to provide a significant public health advantage, public health opportunity.

The e-cigarettes are certainly not risk free. Those risks need to be properly defined through a regulatory process. But there is an opportunity there. And what we announced early on last summer of 2017 was that we are seeking to-- and we've advanced the rulemaking to do this. We're seeking to regulate nicotine levels in combustible cigarettes to render them minimally and not addictive so they can no longer sustain addiction.

At the same time, we allow the e-cigarettes to remain on the market while we put them through an appropriate series of regulatory gates with the notion being that if regular cigarettes no longer have nicotine, smokers would more rapidly migrate off of traditional cigarettes, hopefully off of nicotine altogether. But if not off of nicotine, onto either medicinal nicotine products, the safest form of nicotine delivery. Or if they want inhaled forms of nicotine delivery, onto e-cigarettes.

Again, recognizing that e-cigarettes aren't risk free. But on a risk continuum, nicotine exists on a risk continuum, they are lower risk than combustible tobacco. But what I said all along was that that opportunity and that policy framework couldn't come at the expense of addicting a whole generation of young kids onto nicotine through these same products. And that's, in fact, what we're seeing. We are seeing an epidemic growth. And this is what we spoke to last fall in the use of e-cigarettes by children with fully a 78% rise among high school aged kids in e-cigarettes in over one year, from 2017 to 2018. And really no indication that it's going to abate very quickly in the coming year.

So what we set out to do was implement a series of regulatory steps to try to address the access and appeal that these products have to kids. So we are putting in place significantly heightened age verification requirements for the purchase of products in convenience stores. We're particularly targeting the flavored products because we think the flavored products are a primary vehicle by which these products are appealing to children. At the same time, we launched a series of public education campaigns that we think are very effective to try to educate youth about the risks of e-cigarettes. But I'll say in conclusion that if these actions don't have a very immediate effect on these trends-- and you're not going to reverse these trends overnight. These trends are underway. This has become sort of a fashionable item among kids. You're not going to just reverse that overnight.

But if we don't see this growth leveling off and starting to reverse, I think that this is an existential threat for the entire e-cigarette industry. You know, I find myself stuck in conversations where I'm debating with them the merits of selling cherry flavored e-cigarettes at convenience stores or gas stations where it's readily accessible to a kid. And I think what they really should be contemplating is, boy, if these trends go up another year, my entire product's going to be taken off the market.

Because that is the cold, hard reality. We are going to-- whether it's FDA acting to change its enforcement policy or it's Congress stepping in, if you see another year of 50%, 60% growth in e-cigarette use among minors and you see fully 45% of American kids using some form of tobacco products and you see combustible smoking rates trying to go back up again, that's going to be a public health catastrophe. Nobody is going to have patience to tolerate that for another second. And there is going to be dramatic steps taken.

And so I think that the industry ought to wake up to that fact. We've certainly woken up to that fact and recognized it. And it would be a shame. It would be a shame because the e-cigarettes do represent an opportunity for currently addicted adult smokers in a properly regulated market. We don't want to foreclose that opportunity entirely. And we don't want to impede adults unnecessarily from getting access to these products.

But we are not-- collectively, we haven't done all we can and all we should to address the youth use. You're going to see us take more steps going into this year. We have more enforcement activity underway. But the manufacturers also need to stop fighting some of these steps. And they need to start addressing this more seriously. And, you know, it's one big manufacturer in particular that's driving a lot of the youth initiation on these products.

Well, it's great to hear the vigor that is being brought to bear on this. And I know that in our community there's tremendous support for threading this needle just right, as you describe. So thank you for that.

I want to just take a moment now and say, in general, to Dr. Gottlieb, thanks for joining me today for this ASCO In Action podcast. We are really grateful at ASCO for the strong collaboration that exists between us, the entire oncology community, and the FDA. And we look forward to continuing our work together to make sure that patients with cancer have access to safe and ever more effective treatments.

As a reminder to listeners, you can follow Dr. Gottlieb on Twitter @sgottliebfda. That's one word. You can follow me, a little less exciting I think, @cliffordhudis. And you can follow ASCO @asco. To stay connected with the latest updates on the FDA's work, visit fda.gov.

And as always, we will continue to provide here updates on relevant FDA activities at asco.org/ascoaction. Until next time, thanks again to Dr. Gottlieb and thanks to all of you for listening to this ASCO In Action podcast.

Jan 29 2019
37 mins
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