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Transcription:

Lilian: Hello and welcome to another episode of Avalere Health Essential Voice. Our podcast covers a wide range of healthcare topics. Today’s episode is part 1 in a 3-part series that focuses on how CMS and Medicare coverage decisions may impact patient access.

My name is Lilian Buch. I’m a Principal in the Market Access practice here at Avalere. I am joined by my colleague Mark Von Eisenberg, who is a Consultant in the Market Access practice.

In this episode, we will be providing an overview of national coverage determinations (NCDs), specifically those with coverage with evidence development (CED), and highlight the operational differences across these NCDs with CED. We’ll also identify potential impacts on patient access, strategies and considerations for life sciences companies, and where strategic commercialization strategies may be affected, from the development of evidence generation through coverage.

Medicare is a defined benefit program, meaning that for an item or service to be covered, it must fit within a defined benefit category. So, CMS uses available evidence to fit that item or service within that benefit category. As such, CMS can act as a gatekeeper and one of those gates can be NCD. This mechanism has been utilized over the past few decades and it can include certain guidelines for coverage.

What we’re talking about today is an NCD with CED, meaning that for a Medicare beneficiary to access a therapy or service, it must be covered underneath the clinical trial or a registry.

We have seen a fair number of NCDs with CEDs over the past decade. Currently, CMS is implementing about 21 different CEDs. The Avalere team has delved into the history of many of these NCDs to try to understand the impact on patient access.

Mark, what are some of these notable examples of NCDs, and what can we learn about the patient access implications of those CEDs?

Mark: Absolutely, Lilian. It’s an important consideration to note that meeting CED requirements has taken a few different forms over the years, which highlights how CMS’s decision-making paradigm is dynamic. It can be subject to influence.

One chief example of that is back in 2018 when there was an NCD with CED proposed for CAR T-cell products. This was at the time that the first CAR T products had been approved. Through the public comment process, the CED requirement was actually removed. Stakeholder comments cited that this CED requirement would be a barrier to patient access. It would be overly burdensome, operationally as well as financially. There was already ongoing evidence generation that was looking to answer the same question the CMS CED would look to answer. So, with that rationale, the CED requirement was removed.

In another instance, we’ve seen where registries or prospective trials have been used for longitudinal evidence generation to satisfy a CED requirement as well. This occurred back in 2012 with the transcatheter aortic valve replacement (TAVR) NCD, which still is running today. Folks that are seeking coverage for that procedure can enroll in this prospective registry, and that is the mechanism to fulfill CED for TAVR.

Sometimes we see CED fulfilled with clinical trials. The case that comes to mind there is for off-label use of colorectal cancer drugs in 2003. Products were sequentially added to that NCD until there were 4 products on the NCD. CMS went to the National Cancer Institute at NIH and charged them with confirming and corroborating a set of trials that would be the access pool for patients to receive those products and get Medicare coverage for them. That NCD is still ongoing and the stipulation there is that some products have since expanded their label from an FDA standpoint and are no longer subject to some of the CED requirements. Nonetheless, the CED still runs with those trials.

The most recent example here is the monoclonal antibodies to target amyloid beta for Alzheimer’s disease. This final decision came through in April and something we have not seen before is that the criteria for CED is demarcated by the method in which the product was approved at FDA. So, traditional approval versus accelerated approval. Additionally, we have never seen an entire class of therapeutics, rather than particular products or procedures, be under the purview of a single decision as it is with this new NCD.

So, that’s some of the history of how we’ve seen CED requirements fulfilled

Lilian: Thank you for that historical perspective, Mark. A lot of great learnings there. As we start to think about the potential impact of how patients may be able to access these therapies, it’s really important to think about those operational variances, many of which you described. You can see that, although various NCDs have specific paths forward for patients to access that therapy or service, it’s important to highlight those variances and how those variances can essentially put pressure on the providers, the patients, and also the manufacturers as they think about how to support the patient, to ensure that there is some utilization, because at the heart of it, utilization is important to develop that CED.

You really have 2 ideas here, 2 considerations that manufacturers must think about. Number 1, how do you support the CED and ensure that there is patient access? Perhaps just as important is this idea of the rapid generation of evidence because then you can move through the CED and those requirements can be fulfilled. So, first and foremost, providers and other stakeholders have to think about what it takes to stand up a clinical trial or a registry. Some providers may or may not have that logistical and infrastructure set in place, which can put some negative pressure on access.

Second, you have patient considerations and barriers, which may have to do not only with the type of therapy, but also where treatment can occur. You have pressures on manufacturers and life sciences companies as they start to think about what it takes to support that, so the operational and logistical considerations are not only for coverage, but also much earlier. The idea is that then you start thinking about the confluence of all these NCD operations as being part of your larger and more comprehensive strategy.

Mark, you touched on the fact that while it’s very important to understand coverage as it is under the NCDs, it is also important to think about a regulatory strategy coupled with a coverage strategy. How might a company start thinking about marrying the 2 in the future?

Mark: It’s important to ground this commentary by noting that CMS and FDA have historically had distinct but complementary roles when it comes to the approval and the coverage of products. There’s really limited precedent for the 2 agencies involving themselves in one another’s business.

When it comes to the monoclonal antibody NCD that we were discussing earlier, we see that products, or sponsors in this case, which elected to use the accelerated approval development and review paradigm at FDA will then be faced with a different level of evidence generation and scrutiny for CMS’s confirmation of clinical benefit. What that highlights as an interesting case is that oftentimes there’s going to be, from a regulatory standpoint, regardless of accelerated approval, ongoing evidence generation requirements for regulatory goals. Then in the event of an NCD, or an NCD with CED here, ongoing evidence generation requirements for coverage goals. So, is there a way to mesh those 2 or to be thinking in creative ways to plan evidence generation that could accomplish both of those goals? It certainly is an interesting thought and is something we’ll spend some time thinking more about in our next podcast that will focus on evidence generation plans.

At the end of the day, we’re fighting time to get a body of evidence that’s usable for regulatory or coverage decisions as quickly as possible because patient access is what stands to win or lose here. So, the time required to stand up trials and enroll patients and generate that data while patients are waiting for a coverage mechanism or an access mechanism is what can be optimized coming out of this FDA/CMS engagement idea. It’s certainly something that we will continue to monitor both with this NCD, but also in general as we think about evidence generation.

Lilian: Yeah, thank you, Mark. Very interesting perspective from the regulatory side of the house here. We covered a number of points here, but again, we want our listeners to think about how NCDs or really coverage determinations in general have impact on patient access over time. Generally, with an NCD and even with NCD with CED, there is a path forward for Medicare access, and as that pathway continues to be utilized, it is important for all stakeholders to understand the operational variances and how to implement within the context of clinical trials, but also understand that it is an opportunity for evidence generation and for patient access.

Now, as manufacturers start thinking about evidence generation strategy, it is important to marry up those 2 and have a comprehensive patient access strategy with the broader impact to patient and provider experience. Provider experience becomes relevant too because provider perceptions are important as coverage decisions are made. It is important to understand that those decisions might impact uptake and utilization, and perhaps even broader policy decisions.

So with that, thank you all for tuning into Avalere Health Essential Voice. Thank you, Mark, for joining me today to discuss this important topic and for your insights around the regulatory issues. Please stay tuned for more episodes in this series focusing on FDA engagement and the importance of a tailored evidence generation strategy and its impact on coverage. If you’d like to learn more, please visit us at www.avalere.com. Thank you.