From Evidence to Practice: How NCCN Defines the Standard of Cancer Care

Dale Shepard, MD, PhD:

Cancer Advances, a Cleveland Clinic podcast for medical professionals exploring the latest innovative research and clinical advances in the field of oncology.

Thank you for joining us for another episode of Cancer Advances. I'm your host, Dr. Dale Shepard, a Medical Oncologist and Co-Director of the Sarcoma Program at Cleveland Clinic.

Today, I'm happy to be joined by Dr. Matt Kalaycio, Vice Chair of the Cleveland Clinic Cancer Institute and Chair of the National Comprehensive Cancer Network Board of Directors. He was previously a guest on this podcast a very long time ago with an episode on our response to caring for cancer patients during the COVID-19 pandemic. That episode is still available for you to listen to. He's here today to talk about the National Comprehensive Cancer Network. So welcome back after a very long time.

Matt Kalaycio, MD:

It's great to be back. And I'm glad it's about a different topic.

Dale Shepard, MD, PhD:

Exactly. I gave the titles, but what do you do at Cleveland Clinic?

Matt Kalaycio, MD:

Well, mostly I'm a clinical stem cell transplanter. That's why I was hired and what I've been doing. I've had many roles in hematologic malignancy over the years, but my foundation is in stem cell transplant. Over the years, my career evolved into more administrative work and served as chairman of the department on the board of governors and such. And now as you point out, I'm vice chair of the institute.

Dale Shepard, MD, PhD:

Very good. Well, we're going to talk about the National Comprehensive Cancer Network or NCCN. If people... Variety of different areas might be listening in, what exactly is that?

Matt Kalaycio, MD:

So the NCCN is a consortium of 33 major cancer centers from across the United States who have banded together to create guidelines to help oncologists deliver quality care. So 31 years ago, 13 institutions came together to develop these guidelines, largely to help with insurance coverage. But over time, that has evolved into way more than that. And now the NCCN serves as the standard-bearer for oncology clinical guidelines, not only nationally, but internationally.

Dale Shepard, MD, PhD:

More and more institutions said 32 institutions. What is sort of the interplay between institution itself and NCCN?

Matt Kalaycio, MD:

Yeah, so it's 33. And each member institution is represented at the NCCN on various committees and guidelines panels, and the member institutions fund the guidelines development through dues. So the member institutions participate through this mechanism to allow for the NCCN to exist. That is what the member institutions provide. The NCCN provides in turn opportunities to not only collaborate among the various institutions so that each institution has the opportunity to see what other institutions are doing, and it's largely similar, but also how we work not only clinically, but administratively.

So the operations... So we have something called the Best Practices Committee that all member institutions participate in. And that allows Cancer Institute directors and department chairs to see how other places are dealing with operational issues. That's critically important information. It also provides an opportunity for faculty to serve on these panels where they gain networking opportunities with other similarly-minded experts and provide them not only with that and an opportunity to learn, but to actually give their opinion and participate in the development of the guidelines themselves.

Dale Shepard, MD, PhD:

So institutionally, very important that there's interplay between institutions. How do the institutions get chosen?

Matt Kalaycio, MD:

Well, the first 13 were chosen by themselves. They just sort of came together as a old boys club, to be honest. But since then, if your institution wanted to join the NCCN, they would submit an application. And that application is reviewed by the governance committee. And if your institution meets the standards and criteria that the NCCN demands, it can be admitted as a member. We have added about a member or two a year until about two years ago when we had to stop membership advancement because of a major change in the governance structure. But that change has now completed and we're opening up back up for member institutions, for new member institutions.

Dale Shepard, MD, PhD:

Yeah. So people who sort of are currently practicing oncology, of course, know the NCCN guidelines. Many people may not have any idea how those guidelines come to be. So can you give us a little bit of an idea of how a guideline sort of either is formed or reviewed and updated? What happens? How do we get these?

Matt Kalaycio, MD:

So what happens is each member institution sends a representative to these various panels. And the various panels represent almost 100 individual cancers. So there's a panel for breast cancer, a panel for Hodgkin's lymphoma, there's a panel for prostate... You name your cancer, and often subdivided, and even pediatrics. So these representatives from all these 33 institutions get together either virtually or in person two or three times a year to review the available data. And that data can come from medical journals, but also symposia and just experience.

And this mass of expertise... I have to make sure I make this point, that's across specialties. That's just not medical oncologists. The NCCN specifically looks for radiation oncologists and surgical oncologists, pharmacists, and other oncology providers to make sure there's a wide breadth of expertise in the room. And within that panel, recommendations are made for the treatment.

So, there is already a guideline in place because the institution's been there for 31 years. So, they look at that and see if it needs to be changed. And many times, it does as new data become available, especially these days with a new mutation be identified and a new treatment for that mutation being identified seemingly every year. So, they agree that this particular way of treating is what we recommend. And then that recommendation is sent back to the member institutions for everyone at that institution to weigh in on and agree with or disagree with and make comments on. And then it goes back in its final state published. And in the past, it was published as a PDF, which is pretty unwieldy, but it worked. And it was hard to navigate.

But now the system's digitized or being digitized, many of these are now digitally available and with an AI search feature, which is making it a lot more user-friendly. And so, making those newly formed guidelines available for anyone who wants to use them. And importantly, they are updated as often as every six months, but at least annually.

Dale Shepard, MD, PhD:

There are things... I treat sarcoma. There's an absence of data oftentimes for many, many things. How do the committees consider data from trials, consensus, real world evidence, expert opinion? How do those things get weighed?

Matt Kalaycio, MD:

I suspect that is different from panel to panel. And each chairman of the panel has a different way of running that. And you could imagine five oncologists in a room reviewing a single paper, you're going to get five opinions about what that paper actually meant. But across 33 people, there's a hammering out of vociferous interpretations of that data to come to a regression to a mean. And ultimately a practical, pragmatic approach usually emerges where there's more than one opportunity for treatment. An important part of each guideline is the recommendation for a clinical trial. So, if a clinical trial is available, the NCCN recommends it. They don't recommend individual clinical trials, but they recommend investigation to help address these patients who don't have a clear pathway that's recognized by quote unquote, "experts."

Dale Shepard, MD, PhD:

And then most of the recommendations are options, not necessarily a particular therapy.

Matt Kalaycio, MD:

Yeah. And the NCCN guidelines are purposely non-specific with regard to what you can do. There's a list of things that practitioners could choose from, and they wouldn't be wrong in choosing any of them. They could be prioritized and they often are by level of evidence, but they're not trying to prohibit certain treatments. They're trying to make practitioners comfortable with the treatments that currently exist so they feel comfortable that it's the right thing to do.

Dale Shepard, MD, PhD:

Because NCCN guidelines are oftentimes used for coverage from insurance, how do you navigate pharma pressure to get onto NCCN guidelines?

Matt Kalaycio, MD:

Yeah, so this is important. So, the Centers for Medicare and Medicaid Services, CMS, uses NCCN's clinical standards as a mandatory foundation for cancer care coverage. So that relationship with CMS informs often what other payers will do, but that is a huge responsibility. And in order to maintain the integrity of the process, the guidelines panels are behind a firewall such that only member institution dues fund those guideline panels meetings. So they'll travel the support, the employees who develop those and put them in the PDFs and create the digitization and all that. That's all paid for by member institution dues. Pharma support goes for other things at NCCN, but not the guidelines panels. That's important. The net separates NCCN from other consensus panels that are developed by other organizations where conflict of interest is not always so tightly controlled.

Dale Shepard, MD, PhD:

Has there been a shift recently? So historically everyone would just go to NCCN guidelines and say, "I have disease X. How do I treat it?" And they pull up the guidelines and they're very easily accessible online. How have things like OpenEvidence and the ability to look in other ways to quickly synthesize data and maybe even newer data, how is that affecting the way people look at guidelines?

Matt Kalaycio, MD:

Well, it's impacting them dramatically. So, like I said, historically, the guidelines from the NCCN have been difficult to manage, but it's really easy to put a query into OpenEvidence. In the last year, NCCN has opened its guidelines to OpenEvidence. And so they're connected. If you go on OpenEvidence-

Dale Shepard, MD, PhD:

Yeah, it actual has a little table.

Matt Kalaycio, MD:

... there's a little thing there. And often there's an advertisement from the NCCN CEO saying that, "OpenEvidence is awesome and we're great and together we're even better." That kind of thing. And so if you put in a query into OpenEvidence, it will often come back with NCCN guidelines, including... I've seen cut and paste clips of the actual algorithm.

Dale Shepard, MD, PhD:

A little schema.

Matt Kalaycio, MD:

Yeah. It's right there. And it's correct. It's taken directly from the guidelines. It's a wonderfully easy way to access something that was previously not so easily accessible.

Dale Shepard, MD, PhD:

Tell me about the NCCN Foundation.

Matt Kalaycio, MD:

The NCCN foundation, you can consider it as the philanthropic arm of the NCCN. And here, pharma and individual sponsors do help with the support. It was created by the NCCN in order to help fund certain priorities, the most important one being the patient guidelines. So the guidelines we've spoken about so far have been for practitioners, providers, you and me. But the patient guidelines are for patients. They're written in lay language, and they are for all of the various panels. They're created separately and they're translated into several languages, and they're updated also every year. They're not digitized yet, but with enough support, they will be. So that is one feature of the foundation that is, I think, a critically important and often overlooked feature of NCCN. The other thing it does is fund young investigator rewards. There's about four or five young investigators annually who have been funded through this foundation.

Just this year, the foundation has endowed an award that will be repeated annually. So we don't have to scrounge for money every year and then decide how many people we can fund. This is something that will help young investigators access money for research that they might not otherwise be able to get. And this is limited to member institutions and yet another advantage of being part of the NCCN.

Dale Shepard, MD, PhD:

You mentioned patient advocacy. Does patient advocacy play any role whatsoever in the treatment guidelines? Because sometimes we kind of narrowly say, "Tumor's smaller, that's good." But it's maybe there's associated toxicities and things that sometimes those advocacy groups are like, "Hey, shrunk my tumor, but wait a minute."

Matt Kalaycio, MD:

Yeah, so that's a great question. And in fact, in the last five years, I think the NCCN has begun to include patient advocates on their guidelines panels. Two of my patients serve as patient advocates on guidelines panels. It's a wonderful experience for them, if not intimidating. But it's also great for the providers in the room because there's a patient there and that helps them focus their thoughts.

Dale Shepard, MD, PhD:

Yeah, it's intimidating for the providers. They're like, "I need better … decisions."

Matt Kalaycio, MD:

Or, "And I better not say the wrong thing right here in front of a actively treated patient." So not only are patients represented in the panels, but the NCCN itself has a policy and advocacy arm through which they try to influence government policies. Like I said, CMS depends on the NCCN, and we want politicians and the government as such to recognize that that's an important relationship. There's another thing that I wanted to make sure I brought up, and that is that the NCCN just this year developed something called the Advocacy Academy with the idea of teaching cancer physicians policy and advocacy skills.

One of our own fellows has been elected to this inaugural academy that will start this year. So, the NCCN recognizes that although we can hope that our guidelines are taken up and recognized as representing the best quality evidence and adopted, that won't help if what we recommend isn't paid for or available to our patients. So, advocacy and policy has become... I wouldn't say the most important aspect of NCCN's mission, but an increasingly important one.

Dale Shepard, MD, PhD:

That's fantastic. So, you've been in leadership within NCCN. What's the thing you're most proud of?

Matt Kalaycio, MD:

I have had the privilege of serving as the chairman of the board of directors for the last two years. And in that two-year period of time with the help of Crystal Denlinger, the CEO, who was newly elected as CEO when I came onto the board, in the last two, three years, we've done some things that I'm proud of. One is that we have completely overhauled the governance structure. The original charter of the NCCN made each member institution have two representatives to the board of directors. That was fine when there were 13, but when there were 33 member institutions, that meant there were 64 members of the board of directors. That was just untenable moving forward. We could not add new member institutions. So we had to reconfigure the governance. We did this with an outside consulting firm, but ultimately had to change the structure of the whole thing.

And now the board of directors is much smaller and relatively independent of the requirement for member institutions. There's still a representative body for the member institutions, but from that body come a much smaller board of directors that makes it much more nimble, much more efficient, and it's scalable so that we can now add member institutions again. So that's number one.

Number two was the digitization. An enormous project that I didn't have much to do with, but you had to get the board of directors to agree to these things to fund it and all that. So that happened. And then the OpenAI thing, which didn't have much to do with the board of directors, but it happened under our watch. And the latest thing is this new search feature, which allows regular language inquiry into the guidelines so that you can find what you need faster. That may have happened too late because OpenEvidence queries are probably going to overtake that.

Dale Shepard, MD, PhD:

That's fantastic. So many people know about NCCN kind of the way of like, "Hey, I'm going to go look at guidelines."

Matt Kalaycio, MD:

So the guidelines panels not only provide guidance as to the therapy that should be employed, but they also provide guidance on the supportive care that comes with it. So if you've never given a certain regimen before, and that happens these days, there's now... Well, there always has been additional information in the guidelines to help with the supportive care that's required. Anti-emetics, growth factors, whatever. And I think that's a often overlooked part of the guidelines that I want to make sure the listeners avail themselves of.

With regard to the member institution benefits, the guidelines are available through the most common electronic medical records as order templates. And so a institution, whether member institution or not, can obtain these order templates from NCCN. And you've got built-in NCCN concordant order templates in the electronic medical record. That has the opportunity to provide a lot of efficiency for providers who don't have access to such kind of templates and when a new regimen comes out, they don't have to try to figure out how to order it, it comes from NCCN as a template that make their application of that treatment much easier.

Dale Shepard, MD, PhD:

It's just important from a quality and safety standpoint.

Matt Kalaycio, MD:

For sure.

Dale Shepard, MD, PhD:

Yeah. Appreciate all the insights.

Matt Kalaycio, MD:

I don't think people realize that's a $50 million nonprofit that is internationally recognized and their products are used across not only the nation, but the world as the source of information for oncologic policymaking. It's quite the institution and I'm very happy to be part of it.

Dale Shepard, MD, PhD:

Yeah. Very good. Well, thank you.

Matt Kalaycio, MD:

Thanks, Dale. Good to be back.

Dale Shepard, MD, PhD:

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