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.