MolDX: Molecular Testing for Solid Organ Allograft Rejection Open Public Meeting - September 20, 2023 - JF Part B

Kari DuPreez:
Welcome to the Open Public Meeting for the proposed Local Coverage Determination (LCD) MolDX: Molecular Testing for Solid Organ Allograft Rejection, DL38629 for JE and DL8671 for JF.

Before we begin the meeting, I would like to make the following announcements. This meeting will be recorded. The recording and written transcript will be posted on our website following today's meeting.

All lines are currently being muted and will remain muted throughout the meeting. Only those who have registered to speak will be allowed to comment on the proposed LCD today.

For the presenters, your line will be opened when it is your turn to speak. Make sure you are not on mute within your system, or we will not be able to hear your comments. You should be prepared to begin your presentation immediately when called upon. By signing in today, you are giving consent to the use of your recorded voice and your comments. Please be mindful of sharing any personal health information during your presentation.

In addition to comments that are made today, all comments should also be submitted in writing. All written comments received will be recorded in the Response to comments article.

I will now turn the meeting over to Dr. Barry Whites. Dr. Whites you may begin.

Dr. Barry Whites:
Thank you very much. Can you hear me, OK?

Kari DuPreez:
Yes. We can.

Dr. Barry Whites:
OK. Great. Thank you. Welcome, everyone. This open meeting, as she mentioned, is is concerning the molecular testing for solid organ allograft rejection. You wouldn't be on this meeting unless you're wanting to comment, unless you were familiar with the policy.

Just to hit some of the highlights, this is a policy that has had some controversy, and this is an attempt to try to resolve some of that controversy based on policies that have preceded this one.

We have coverage guidelines, and the guidelines are contained within that definition that we use in the guidelines, so there will not be any confusion.

Medicare is going, or Medicare and this contractor will provide limited coverage for molecular diagnostic tests used in the evaluation and management of patients who have undergone solid organ transplantation, Tests informed decision making, along with standard clinical assessment of the patient. It would be ordered by a qualified physician, considering the diagnosis of acute rejection, helping to rule out this condition when assessing the [inaudible] results of a diagnostic biopsy.

They are considered not as an item themselves, but to be used and considered along with clinical evaluation results. Molecular tests that are, such as transplant allograft rejection status are covered and there is a list of six bullet points that of intended use and the test must be about one of the following clinical status determinations, and that is acute rejection or cellular antibody mediated rejection.

The policy is, this also noncovered items, or not items, but on conditions of which the items are not to be or not be covered. Those are all listed in several bullet points in here.

The summary of the evidence is likewise listed in the policy, where we came to the conclusion that we did come to and the Contractors Advisory Committee, we had two, one on the heart and lung and a second one was conducted on additional organs.

Purpose of this meeting is to allow, and this is truly a purpose to try to gather information on objection to the test.

Not only do we want your feelings, but we also need for you to provide documentation and the documentation needs to be, hopefully, in the form of peer-reviewed clinical trials or at least peer reviewed articles.

This policy, we know is controversial, we know it's going to take some explanation, and that's what we are when we have this notice and comment period. This notice period, it is 45 days long, and it will be. Excuse me, the comment period is 45 days long and will end on the 23rd of this month, so need to get the information, if you haven't already into us by the 23rd.

We then have a minimum of 45 days to respond and our comments and response to comments will be published. The reasons for a comment likewise will be published, and the changes that will come out will then be afforded an additional 45-day notice period prior to its initiation.

With that introduction, we'd like to begin with our presentations. Dr. Jeffrey Teuteberg, you are up to bat.

Dr. Jeffrey Teuteberg:
Thanks so much for the opportunity to speak today, do you have my slides up?

Dr. Barry Whites:
Yes sir.

Dr. Jeffrey Teuteberg:
Great. Now if you could move forward.

So, the three issues that I wanted to bring up today, and the proposed this decision, was the first the use of molecular diagnostic testing being restricted to the frequency that centers use biopsies. The second is that molecular testing should not be used concomitantly with a biopsy and the third is that, for any given patient, encounter, only,one, molecular test can be used.

Next slide.

Dr. Barry Whites:
Excuse me, just one minute. To mention the question that had come up. The question of how long does each speaker have? We typically ask that we limit these to eight minutes, but there's no, no set ironclad in-stone rule. We would try to keep it that short if you can, if you cannot and you cannot get all you want to talk in that, that is fine. We're not going to be limiting to that but if others are, have already presented the point that you're trying to make, you can, you can just issue that, you know, you agree, and the same data, it would be much appreciated.

So, there is no particular limit. We do hopefully a two-hour window and we can go over that if we need be. But hopefully it is not a definitive item. So, if you will keep that in mind, I would certainly appreciate it. And I'm sorry to interrupt you to please go ahead.

Dr. Jeffrey Teuteberg:
Not a problem. Thanks so much. So, we certainly seen with our use clinically or molecular surveillance that it's definitely critical to the use for the management of patients outside of where we typically do a surveillance biopsy. Specifically, it's really used to help make transplant medicine and heart transplant medicine in particular, in this case, much more like precision medicine, focusing in on that particular patient, and making sure we're managing that particular patient as precisely as we possibly can.

Next slide.

And to kind of give this some context, so for most of our patients, there's a small proportion of them that are higher risk, and they're typically younger, and unfortunately, many of those are young women, and those patients, we need to maybe have higher degrees of immunosuppression, and we may need to keep a little bit closer eye on them and doing that with biopsy alone is impractical.

For the vast majority of the rest of the patients, they tend to be lower risk and for our patients, particularly those who are older, who are more likely to have toxicity as a chronic immunosuppression, it's really important that we establish their being low risk, and that allows us to back off and immunosuppression, and hopefully mitigate many of those adverse events from the chronic immunosuppression.

Next slide.

The other thing that molecular testing allows us to do is to catch things early and we like to catch it before there's histological evidence of rejection or donor specific antibodies, and certainly before patients develop left ventricular or biventricular dysfunction and heart failure symptoms.

Next slide.

And we've seen that with some of our large national databases. This is data from Shore, a large national database of heart transplant. Patients being managed with noninvasive molecular testing, and these are a couple dozen patients who have biopsy proven rejection and we can see elevations of their cell free DNA starting a couple of months prior to rejection and that's important because we can interrupt that inflammatory and immune cascade before it gets out of control and more difficult to manage.

Next slide.

That's important because when you look at patients who have rejection, those who have rejection without hemodynamic compromise, do better over time instead of sort of overall survival, not to mention many of the downstream effects of graft dysfunction and vasculopathy.

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Rejection is still a problem throughout the lifetime of the graft, even though we sort of only have done our biopsies early on, that's the period of high risk, but it's not the period of only risk, and patients still get rejection throughout the lifetime of their grafts and that can result in adverse events and hospitalization and cost, as well as mortality.

Next slide.

The new guidelines, I think, sort of capture the spirit of, although they came out, I think, a little bit too late to be included in the bibliography. But, you know, they do mention that routine tests and clinical visits are crucial for the success of heart transplantation and that's a class one recommendation.

And if you hit the button again.

You know, and the reassurance of these negative surveillance results with noninvasive testing outside the biopsy window are really, really critical to us having the ability to reduce toxic immunosuppression and manage our high-risk patients as well.

Next slide.

You know, the other thing is the biopsies, or it can be harmful. We know from a lot of studies over many years that you can develop severe TR anywhere from 10 up to 25% of patients and that results in graft dysfunction and symptoms and can often lead to things like valve surgery to correct it.

Next slide.

We also know the biopsies are inaccurate, not only because they only sample a very limited area of the myocardium, and we know rejection can be throughout the myocardium and often patchy. But when you have local pathologists compare the results to central pathologist, you can see that from this slide, when the grade is over 2R rejection, something that we would normally augment their immune suppression for, about 40% of the time, the central pathologists actually disagree with those readings and so those patients potentially could have avoided that augmented immune suppression. The flip side of things, about 7% of the time, but still reasonably common, local pathologists don't think there is rejection, and the central pathologists do, and so those patients may have benefited from more immune suppression, but don't get it because of the disagreement in pathology.

Next slide.

And long-term biopsy is just impractical and not really patient centric. We'd like to try and move away from that when you look at 2019 and the distance of recipients from the heart transplant centers, over 20% of them are over one hundred miles from the transplant centers. It's just not practical for patients, in terms of being able to get rides and affording it, and gas and parking, and not to mention things like pain and discomfort, anxiety, from the procedure itself.

Next slide.

So, molecular testing is clearly a suitable candidate to replace most surveillance biopsies. In our program, about 95% of our routine surveillance doesn't result in a biopsy because of the use of molecular testing. But they should also be used in areas where we don't use biopsies because they're either impractical or too risky.

Next slide.

Specifically, I think, extending this surveillance out over the years with molecular testing is reasonable, both to detect rejection, but also again, to specifically help us mitigate some of the chronic, downstream, negative effects of chronic immunosuppression.

Next slide.

The second is that molecular testing should not be performed in conjunction with a biopsy. We often see patients who present with graft dysfunction and often the biopsies are 1 - difficult to get, and if we do get them, they're often bland in relationship to how much graft dysfunction we see. So, it's often useful to get a molecular test to see if there's active rejection happening, maybe this process started just a couple of weeks ago and the patient would benefit from more immune suppression and maybe it happened six months ago, and you just haven't seen them in six months, and they wouldn't benefit from those toxic immunosuppressive drugs.

Next slide.

We're already using multi-modality testing. Our patients get antibodies tested, they get an echocardiogram, they get a biopsy, oftentimes they get an angiogram as well. So, these molecular tests just are part of the picture to help us better take care of our patients.

Next slide.

We can also use it to determine the success of treating rejection. We see that cell free DNA goes up with rejection, whether antibody or cellular mediated and comes down after treatment. Many of our patients can't come back for a two-week biopsy where it's too difficult for them to get back or their initial biopsy was sort of bland and the face of graft dysfunction, and so it's hard to know whether a treatment worked or not. Noninvasive testing is really a boon to determine the adequacy of treatment.

Next slide.

Lastly, we're already doing multi-modality testing. And so, limiting to only one molecular test per visit doesn't seem to make a lot of sense for acute cellular rejection reviews and gene expression profiling in cell free DNA, for AMR, we're using things like antibodies, and cell free DNA. And hopefully we can start to use some of these tests to look at some of the more difficult chronic problems like CAV and allograft dysfunction.

Next slide.

So, in summary, again, thank you for the opportunity to present today and just some considerations for changes to the language. So, in terms of the test frequency, we would suggest that molecular surveillance is really critical for patient management and shouldn't be limited to instances where a surveillance biopsy wouldn't have been performed.

The next is the concomitant use of biopsy in molecular testing. We agree it shouldn't be used concomitantly all the time, but the simultaneous use of biopsies and molecular testing may improve the diagnosis and patients who present with graft dysfunction.

And lastly, in terms of the number of molecular tests you can use. I think we've seen clinical evidence and our clinical experience to date has shown that these molecular assays are complementary to one another and provide data on various aspects of the alloimmune response and graft injury simultaneously. That allows us to better take care of our patients.

Thank you so much.

Dr. Barry Whites:
Thank you, sir. Again, we have your presentation, the articles, if you could get those in, and the language, all of this in writing to us, it would certainly be appreciated.

Dr. Woodward would be our next speaker this afternoon. Dr. Oakes is going to take over for introducing the next speakers and participant in this meeting. Gary, thank you so much for doing that. Dr. Woodward, please proceed if you're ready.

Dr. Robert Woodward:
Thank you. Thanks for the opportunity to present today. I am Robert Woodward, I'll be presenting on behalf of CareDx, if you could move forward one more slide, please. At CareDx, we are 100% committed to transplantation, with over 20 years of innovation in and transplant patient care.

Our first Medicare approval was in 2006 for gene expression profiling with immune status of heart transplantation and we led the industry with the first approved coverage of donor derived cell free DNA to measure graft injury in kidney, heart, and lung and the first approved coverage or multi-modality testing.

Next slide, please.

I'll go through the next slide quickly as this was in the previous presentation but there's a significant need for these advanced molecular tests and transplantation, which is a lifesaving treatment. Transplant carries a lifelong risk of immune mediated rejection of the transplanted organ. When rejection is currently diagnosed by histopathology of a tissue obtained from an invasive biopsy. However, surveillance by biopsy, is invasive, and, therefore, undesired, while surveillance through assessment of functioning, is insufficient to identify rejection early enough.

Molecular tests to significantly reduce the dependence on biopsies, improve diagnostic capability and enable noninvasive detection of subclinical rejection that occurs before function is impacted.

Next slide, please.

These tests are proven so valuable that they have been quickly adopted. Just those provided by CareDx are used in over 90% of heart centers, 75% of kidney centers, and 65% of lung centers.

The latter within just two years of launch, many consider these to be standard of care and in heart transplant where there are guidelines that exist. The clinician society includes these tests in the guidelines.

Next slide, please.

The proposed revisions to the LCD introduce changes in language that we view as changes to coverage. These changes were initially improperly introduced in the associated billing article in March of this year, a concern also noted by physician professional societies. Our first recommendation is that these changes be rescinded immediately until the full LCD process is completed. That process, including the comments today, the written comments that are due this week and your complete evaluation until the LCD is finalized.

Next slide, please.

The proposed revised LCD changes coverage in three major ways. First, it restricts surveillance use. Second, it prohibits testing close to a biopsy and third, it prohibits the use of multiple tests with unique contributions at the same encounter.

The LCD itself incorrectly states that these revisions are simply for clarity of coverage and are not changes to policy. However, a question that should be asked is whether new evidence has emerged to support disturbing the longstanding coverage policy. It has not, the evidence supporting this established use of these tests has only increased in the past three years.

Next slide, please.

So, digging into each one of these, the first of these major changes that we'll comment on is the restriction on surveillance use as described in the box. Since the first LCD that covered AlloSure, which is our test for donor derived cell free DNA, the LCDs have always provided a broad coverage for surveillance that is not tied to a biopsy.

In fact, on the first LCD, Noridian replied to a comment with an official statement that AlloSure may be performed at a frequency established for other noninvasive tests, for instance, 4 to 6 times in the first year, and 2 to 4 times in subsequent years.

More recently, the initial draft of the current foundational LCD included the language in lieu of biopsy, but that was subsequently removed after public comment and MolDX and Noridian response that they were not tying its use to the need for a biopsy.

The proposed LCD text, which is shown at the bottom in red now states that, for surveillance use, the testing frequency must be no more frequent than the center specific surveillance biopsy schedule.

The accompanying billing article states that surveillance testing is only compliant if the patient would otherwise receive a surveillance biopsy.

Next slide, please.

This change was made not based on evidence, but despite the evidence that these tests have demonstrated ability to identify subclinical rejections.

The early detection of rejection before the rejection impact's function allows earlier therapy and can lead to improved outcomes.

Kidney guidelines which have not been updated since these tests have been available, recommend treating subclinical rejection, despite not recommending an invasive surveillance biopsy.

As mentioned, the heart guidelines acknowledge the importance of surveillance with these tools. In lung, surveillance biopsies have the most significant complication rates, further limiting use for surveillance despite the great need.

Limiting the use of molecular tests to the biopsy frequency is flawed because the risk profile of a noninvasive blood test is fundamentally different from an invasive procedure.

We recommend maintaining coverage for surveillance use, possibly even memorializing its use consistent with prior official comments.

Next slide, please.

The second major change is the restriction based on time of biopsy. There are no limits in the current LCD in this regard. However, the proposed LCD states that these tests are not covered by Medicare if the patient has undergone a recent biopsy with a definitive diagnosis or has a planned upcoming biopsy. The proposed billing article also states that molecular tests and biopsy cannot be performed simultaneous.

Next slide, please.

Published evidence supports the use of these tests concurrent with biopsy for several reasons. In kidney, cell free DNA has been demonstrated to inform on outcomes in patients with biopsy diagnosed low grade T cell mediated rejection. In both heart and kidney, there are publications demonstrating the ability to use cell free DNA to monitor treatment response. This use requires comparison to the level of cell free DNA at the time of the biopsy confirmed rejection. We recommend this new restriction be removed in favor of physician directed, evidence-based use of these tests alongside biopsy.

Next slide, please.

The third major change is the prohibition of multi-modality, which is the use of use in the same visit of tests that offer complimentary information. This is enabled in the current LCD; however, the proposed LCDs strikes the phrase "unless a second test is reasonable and necessary" as a jump to the first. This leaves the sentence to end with the phrase, "only one test may be performed."

The use of two complimentary tests has been validated in both heart and kidney and has evolved to the standard of care in heart transplantation, specifically, mentioned in the latest guidelines. Paired testing offers better diagnostic performance for active rejection. We recommend the current language, or similar, be retained, to enable physician settlement to choose the appropriate test or tests for a given transplant recipient, based on the evidence and the need.

There have been four other changes we will address in our written comments. One comment, regarding interpretation of surveillance use of biopsy without recognizing originating biopsy practice and the risk profiling biopsy. Two comments recommending definitions that incorporate language from the latest billing article for consistency, and the fourth comment on the over specific restriction on a comparative biopsy standard, I won't go through these in detail today, so please advance three slides to the final slide.

Thank you.

So, in summary, the proposed LCD changes coverage in ways that limit physician judgement and negatively impact care for organ transplant recipients that require lifelong monitoring to achieve long-term graft survival. Revision to the LCD is the correct process to introduce such changes, but this particular process is compromised by the earlier implementation of the same changes in a billing article which does not and did not go through public comment.

We recommend rescinding the billing article changes until this current process is finished. Ultimately, the longstanding coverage for these molecular tests should be maintained to allow physician judgement based on evidence and patient need, for surveillance, for concurrent use for the biopsy and for most multi-modality use of complimentary tests. The data support these changes covered by the existing policy. I'm sorry, the data support these uses that are covered by the existing policy and no data supports the proposed changes.

Thank you for your time. The evidence that I referenced today is listed here and we will submit this information in the form of a comment letter later this week as requested.

Dr. Gary Oakes:
Thanks Dr. Woodward. Dr. Stephen Potter are you available?

Dr. Steven Potter:
Yes, you just unmuted me, so now I'm, now, you can hear me. Can you hear me, OK?

Dr. Gary Oakes:
Yes, sir.

Dr. Steven Potter:
All right. Can I see the first slide, please? Well, thank you very much for allowing me to speak during this public comment process. I'm here representing the American Society of Transplant Surgeons, commenting on proposed revisions to molecular testing for solid organ allograft rejection and to Dr. Whites point, um, I have multiple references in this talk, but we also, will be submitting expanded comments later this week, through your pathway.

Next slide, please.

So, our societal disclosures, CareDx, Eurofins, and Natera have provided financial support, two ASTS in the past.

Next slide.

So, the local coverage determination review process is the proper process and venue for changes to coverage. In March ASTS requested delay of the revised billing article in favor of the LCD process and, we want to thank you for engaging in this LCD revision process and provide the attendant an opportunity to give public comment.

The proposed LCD revisions were issued in August, and we're appreciative of the admission that a billing article was not the correct mechanism to introduce significant changes to the LCD.

We are concerned that the billing article still in effect. The fact that the revised billing article is still in effect, despite an absence of public debate, is at odds with both transparency and public process and with the comments you've received from your community. Our comments today regard the proposed LCD and the existing constraints to optimal patient care imposed by the billing article.

Next slide, please.

So, the molecular diagnostic testing questions are an emerging standard of care. Some of the proposed LCD changes are inconsistent with the input provided by experts at the Clinical Advisory Committee or CAC meeting held in November of 2022. There is significant evidence of the clinical validity of these molecular tests. There's widespread acceptance for utility and clinical decision making.

The CAC supported expansion, rather than limitation of Medicare coverage for these tests, and these tests may provide the ability to improve patient and allograft survival.

Particularly long-term allograft survival, which has been an area of great concern to the transplant community, and, obviously, to transplant recipients. The proposed changes to the LCDs substantively change coverage and the proposed coverage changes are not supported by evidence in the peer reviewed literature.

Next slide, please.

So, the proposed LCD would restrict surveillance use of molecular testing to the direct replacement of existing surveillance biopsy protocols, and I've quoted the language from your proposed LCD above. Surveillance biopsy is used to detect kidney subclinical rejection, but surveillance biopsies are only performed by a small minority of centers. Guidelines recommend treating subclinical rejection, recognizing it, association with estimated eGFR decline, chronograph the injury and allograft loss. There is strong correlation between the covered molecular tests in kidney subclinical rejection and there are no societal recommendations regarding surveillance biopsy to look for subclinical rejection. Leaving us in a conundrum without reversion to the prior 2021 LCD.

Next slide, please.

Heart transplant centers have reduced the frequency of surveillance biopsy dramatically by utilizing molecular testing and acknowledge the importance of rejection surveillance using molecular testing in their guidelines.

Molecular testing is not subject to interobserver variability or sampling errors as biopsy is and may actually have superior sensitivity and specificity in this difficult patient population than biopsy does. The proposed LCD conflates the risk benefit calculations for a noninvasive blood test with an interventional procedure that can cause significant harm. Molecular testing allows surveillance testing when biopsies were not typically performed due to a more favorable risk benefit ratio.

Transplant professionals should retain the ability to determine the frequency of molecular surveillance testing in partnership with the patients under their care based on those patients' immunologic risk and other risk factors that they face every day.

Next slide, please.

The proposed LCD would restrict molecular testing based on timing relative to biopsy. Again, exerted the relevant language. Levels of donor derived cell free DNA obtained concurrently with biopsies demonstrating low grade cellular rejection, have shown significant prognostic utility.

Improvement in donor derived cell free DNA after treating rejection is well documented in both kidney and heart recipient populations. Therefore, a donor derived cell free DNA level obtained at the same time as a biopsy, can evaluate the adequacy of response and preclude the need for follow-up biopsy to document successful treatment.

Information from concurrent molecular and histology testing, can help clinicians make decisions about immunosuppression management, long term prognostication regarding Allograft survival, individualization of immunosuppression for those patients, a need for or timing of repeat biopsies.

Next slide please.

The proposed LCD would prohibit the concomitant use of multiple tests. Definitive diagnosis of disease frequently requires comprehensive multimodal laboratory investigation. Multimodal assessment, utilizing donor derived cell free DNA, and gene expression profiling in solid organ transplantation provides information on distinct biological processes. In the case of donor derived cell free DNA, information is provided on allograft injury, in the case of gene expression profiling, information about recipient immune activation is provided. Paired testing demonstrates better diagnostic performance for active rejection diagnosis in both kidney and heart recipients than single technology platform testing alone.

The existing LCD includes language recognizing that, and quote, "combining both doner derived cell free DNA and gene expression profiling may further improve graft rejection determination" end quote. And further states, quote, "these molecular tests have different strengths and weaknesses and can be leveraged for different populations" end quote.

The coverage criteria should allow providers latitude to determine the appropriate test or tests for a given patient.

Next slide, please.

So, in conclusion, it's really all about patient care and patient survival. Prior to molecular testing for allograft injury and immune activation, we in the transplant community had been performing organ surveillance in much the same way for several decades. The results obtain with legacy surveillance techniques, including urine protein assessment, serum creatinine, and tissue biopsy were and continue to be suboptimal.

The failure to meaningfully improve long term transplant survival despite massive improvements in short-term patient and Allograft survival remains one of the cardinal failures of the transplant endeavor. Molecular diagnostic testing may help us unlock significant gains in long-term patient and allograft survival and are already widely used emerging standards of care and the management of our patients.

We urge you to support the utilization of these innovative tools with demonstrated clinical utility in the complex and vulnerable patients that we care for.

Thank you very much.

Dr. Gary Oakes:
Thank you, Dr. Potter, appreciate the presentation.

Next up is Lorrinda Gray-Davis from Transplant Recipients International Organization.

Lorrinda Gray-Davis:
Yes, Hi, this Lorrinda. Thank you for listening to transplant patients and hearing our testimonies as evidence. My name is Lorrinda Gray-Davis, I'm the president of Transplant Recipients International Organization (TRIO). I am five years post liver transplant and heading towards a kidney transplant due to the lack of innovation in post-transplant medication. I'm concerned for the constituents of TRIO when it comes to the proposed coverage changes outlined in the proposed LCD.

The proposed changes limit patient access to innovative tests for surveillance, nor require patients to exhibit symptoms of rejection before being eligible for these tests. This poses a significant threat to the well-being of transplant patients, and the advancement in medical innovation. Transplant patients are already dealing with complexities and challenges of organ transplantation. When it comes to post-transplant care, this often means undergoing traditional invasive biopsies, because there have been no other options.

Biopsies are burdensome to patients, painful, expensive, and can come with complications and often occur too late to successfully treat the issue. Innovative tests for surveillance play a crucial role in the post-transplant journey by providing early warning signs of rejection or other complications even before noticeable symptoms emerge.

Innovative tests have the potential to revolutionize how we monitor and manage, transplant patients, making care more precise, efficient, and ultimately improving patient outcomes.

They represent one of the most important advancements in this space in decades. If access to these tests is restricted, researchers and developers may be discouraged from investing in further advancements in this area, resulting in a standstill in progress.

Now is not the time to put patient access at risk and stifle innovation in the field of post-transplant care. It is essential that we maintain an environment that fosters innovation, supports early detection, and ensures the best possible care for transplant patients.

I respectfully request that you take into account the concerns raised by transplant patients, medical professionals, and advocates like me in making your final decision. on this matter. The health and well-being of transplant patients should remain at the forefront of any policy changes in this field.

Thank you for your attention. I look forward to seeing and to see a decision that prioritizes the need to transplant patients in a courage, has continued innovation and post-transplant care, and we will be submitting a written comment. Thank you.

Dr. Gary Oakes:
Thank you and thank you for presenting on behalf of the patient. That is always important.

Dr. Kush is not able to be with us. Dr. Keller, are you available?

Dr. Brian Keller:
Yes, I am here. My name is Brian Keller, an Assistant Professor of Medicine at Harvard Medical School, and the Medical Director for the Lung Transplant Program at Massachusetts General Hospital.

First, I'd like to start by saying that I agree with and fully support all of the information presented by the previous speakers, and while most of that information was focused on data from the heart and kidney transplant world. As a lung transplant pulmonologist, I'd like to highlight some of the differences and nuances that we face with lung transplant patients and monitoring there are allograft health.

So, like transplant patients, face not only allograft rejection, but in section of the allograft due to the exposure of the allograft directly to the environment. We utilize molecular tests such as cell free DNA, to help us identify the health of the graft and to determine when the graft is not functioning as well as it should be. However, unlike heart and kidney transplant patients, elevations in cell free DNA and lung transplant are not solely related to allograft rejection but could represent infection. Therefore, the proposed LCD language that limits the use of molecular testing in place of a biopsy really does not help us. Because we're only detecting allograft injury in our patients and therefore use of a biopsy may be warranted and may be complementary.

I would also like to talk about a couple of unique situations that are lung transplant patients face in which the use of cell free DNA is complimentary and could potentially replace a biopsy. Sometimes our patients are too sick to safely undergo an invasive trans bronchial biopsy. They can't tolerate the sedation; the risk profile is too great for them to safely undergo the procedure. In these situations, we could, in theory, utilize cell free DNA as a marker of allograft injury to help determine treatment and decision making.

Alternatively, when patients are diagnosed with acute cellular rejection or antibody mediated rejection, the use of cell free DNA can be utilized to monitor response to treatment. Oftentimes with acute cellular rejection, historically, what we would do is we would treat acute cellular rejection, and then follow that up with another invasive biopsy a short time later to determine response to treatment. As it as previously described for heart transplant pathological readings, the same issues apply to lung transplant pathological readings.

Agreement between pathologists on biopsy grading varies quite dramatically. Rejection can be spotty and patchy throughout the organ and it's possible to miss picking up rejection with biopsies, and so the use of this molecular testing can allow us to more specifically monitor response to infection as the levels of cell free DNA improve over time.

It can also tell us when our treatment is not working, and we should maybe consider alternative therapy or look for additional causes of allograft injury.

Finally, I'd like to point out that I view these molecular tests not so much as being similar to biopsies and the utilization but being more similar to other tests that we use for monitoring allograft function. Every time we see a patient in clinic, we perform pulmonary function tests that we perform chest x-rays as well as routine lab work and all of that is meant to measure the health of the allograft. This is where molecular testing fits in to lung transplant monitoring. It is a measure of allograft health and a detection of allograft injury and provides insight as to when to proceed to a more invasive test. It also allows us to monitor patients on a more frequent basis, so that we can, as previously discussed, detect allograft injury earlier, and intervene before it becomes a threat to the long-term function of the graft.

I'd like to thank you for your time and the opportunity to present this information as it relates to lung transplantation. I hope you've taken into considerations all of the comments made today, as well as the idea that we really need to be putting patients first and allows physicians and clinicians the bandwidth to make professional decisions that are in the best interest of the patient. Thank you.

Dr. Gary Oakes:
Thank you, Dr. Keller Effected gets you to comment a little bit, we've heard a lot about heart and kidney biopsies in conjunction with the test, how often would you think that using this test would avoid a biopsy of the lung and when might you use it? I won't hold you to, this is just helping educate us.

Dr. Brian Keller:
Yes. So first of all, I will say that, like kidney transplant programs, the use of surveillance biopsies varies dramatically between lung transplant programs and so there's not a standard recommended frequency of biopsies and so, even within programs there may be differences in frequency of biopsy by transplant pulmonologist. So, I think it's hard to standardize it to that.

The way we analyze the tests at our center is we test monthly during the first year, which is the time period where the patients are at highest risk for acute cellular rejection as well as antibody mediated rejection. It helps to guide us in this and if testing shows an elevated level, we will proceed to biopsies sooner and if testing is consistently low and re-assuring that the allograft injury is not occurring, then we may utilize that information to forgo a biopsy.

However, the present time, the experience with the testing, is not sufficient enough to completely eliminate biopsies and for us to feel comfortable that we need to completely eliminate biopsies.

The other thing with lung transplantation is the bronchoscopy. In addition to allowing us to do the biopsy also allows us to collect samples to test for infection, which is not specifically detected with these molecular tests at present. They also allows us to evaluate the airway anastomosis and to evaluate for complications such as bronchial stenosis, which are supplementary to detecting rejection, but have important implications for patient health long term.

Dr. Gary Oakes:
Thank you, sir, is very helpful, much appreciated. Next on the list is Samuel Kirton. I hope I pronounced that right, sir.

Samuel Kirton:
Absolutely. Thank you for the opportunity to be here and I feel like the previous speaker was a perfect segway for a lung transplant patient to offer a view that I hope you will take into consideration.

My name is Samuel Curtain, I Live at Lake Ana, which is near Mineral, Virginia.

I was diagnosed with idiopathic Pulmonary fibrosis on January 31st of 2017. Idiopathic Pulmonary Fibrosis is a chronic progressive lung disease for which there is no cure. At the time, there were two approved therapies which slow the progression of the disease.

There were only two outcomes, first, that as to be eligible for and receive a lung transplant. The second outcome, death is far less desirable.

On July 10th of 2021, I received a bilateral lung transplant. A lung transplant, as you know, is not a cure. It is a commitment to a lifetime of medical surveillance. Shortly following my transplant, my care team began the required surveillance to look for signs of rejection, using molecular diagnostics and a noninvasive blood test specifically, CareDx AlloSure lung product.

I was among the first lung transplant patients to be monitored using AlloSure lung. For the first year following my transplant, these tests were monthly, and beginning in the second year, those labs were drawn on a quarterly basis.

The introduction of molecular diagnostics for post-transplant surveillance provides my care team and me as the patient, a noninvasive method to monitor the health of my transplant. A biopsy of my lung is an invasive assault on the very lungs which provide me the opportunity to extend my life.

During the last two years, noninvasive blood tests provided my care team with the opportunity to identify any early signs of rejection of my donor lungs. Each post-transplant patient's experience is unique in mind is not without exacerbations. For me, three separate exacerbations have benefited from this noninvasive blood test. In the fall of 2022 I had pneumonia, followed by Covid in April of 2023.

Between these two exacerbations my care team discovered my left bronchial stem was closed up or narrowing despite several balloon dilation. The decision was made to add a stent to my left bronchial stem when it narrowed to 3 mm. Following each of these exacerbations, my care team could determine by a simple blood test, whether I was at an increased risk of rejection.

My bilateral lung transplant was fully covered by Medicare and Tricare for life, both federal government insurance programs. It is confounding to me, why Medicare would risk the health of my transplant, by using or insisting on using an invasive biopsy when any risk of rejection can be detected and dealt with earlier using a noninvasive blood test.

Is there any medical procedure where an invasive procedure or test is? preferred over a noninvasive test? Additionally, limiting the use of noninvasive predictive blood test until signs of rejection appear as the potential to further burden, the Medicare and the health care system, when more advanced rejection requires hospitalization for treatment. The use of molecular diagnostics is a medical decision based on a doctor's knowledge of their patients.

The transplant community is more susceptible to the potential risk of invasive testing. What other predictive surveillance is at risk by this type of decision? Mammograms? Colon cancer screening? This testing is vital to the health of the transplant community.

These comments will be submitted electronically as requested and I want to thank you for your time, and the opportunity to share these continents with you this afternoon.

Dr. Gary Oakes:
Thank you, Mr. Kirton. appreciate you, taking time to come out and share with us and best wishes as you move forward. Next on the list, Tiffany Archibald from Community Kidney Care. Tiffany?

Ms. Archibald, are you there please?

Kari Dupreez:
Tiffany, it looks like your self-muted. Are you able to unmute yourself?

Tiffany Archibald:
Yes.

Kari Dupreez:
There you go.

Tiffany Archibald:
Sorry about that. Thank you for including me today and being able to share my testimony on this very important topic for all of us transplant recipients. My name is Tiffany Archibald, and I'm a kidney transplant recipient, actually, a three-time kidney transplant recipient.

My journey started over 20 years ago, as an active athlete, with a healthy lifestyle, all my life, I never could imagine being in the position that I am now and the health challenges that I would experience. After three kidney transplants and several traumatic biopsies, I'm speaking now to shed light on the invaluable role that noninvasive in the molecular diagnostic testing plays for post-transplant surveillance and the overall health of us transplant patients.

I believe access to this testing is a large part of the reason I am here today. Still strong, healthy, and able to share my story. I play collegiate level basketball at USC [inaudible] and after that, I played for a few years overseas. While undergoing a low-risk procedure on my toe, my post-surgical lab showed my kidneys were only functioning at 25% and my only option was transplant. That's where my transplant journey began in 2005. My mother was able to give me one of her kidneys, she birthed me twice. While I am grateful for the second chance at life, it was during that time that I was exposed to the reality of a biopsy.

Biopsy or not just routine medical procedures, they are very traumatic and oftentimes risky for us patients. After 8.5 years with my first transplant, I require another transplant in 2013. My husband was my donor at the time and that process moved very quickly.

I was fortunate up to that point that I did not have to undergo dialysis while waiting for a kidney. My life as a transplant patient changed forever after another traumatic biopsy. I then learned that there will be a better way moving forward to monitor my kidney for rejection.

Going into that biopsy, I was incredibly scared and traumatized from the first difficult experience. I learned that unfortunately the biopsy that I had done did not successfully collect any of the kidney tissue, only medulla. Despite them invasively prodding and moving through my kidneys during the procedure, it was ultrasound assisted, and there were several medical professionals in that room. I was frustrated, scared, and confused.

I really get emotional talking about the discovery of noninvasive testing, because I never could have imagined an option like this, would exist for me after navigating those traumatic biopsies.

I was given the option to start using the cell free DNA test AlloSure after that unsuccessful biopsy. It amazed me that a simple blood draw, like many routine labs I was doing anyway, could monitor my kidney health successfully and potentially detect signs of rejection.

I was fortunate that if I needed to, I had the resources and support to easily access inpatient medical care for surveillance and biopsies. Not everyone has that luxury, though and the convenience of a blood test at home is a game changer for every patient doing their best at their lives, to preserve their transplant functioning to have a healthier lifestyle.

Fast forward to just five months ago, after receiving my third and my most recent kidney transplant, this was my first time that I had to endure dialysis among other health challenges that caused me to be hospitalized. Now that I'm on the other side of this third transplant, I continue to be grateful to have access to the noninvasive testing that monitors my transplant.

I couldn't imagine what it would be like to have restrictions on access to all my AlloSure tests, not knowing if I'm being tested frequently enough or if I would be able to shoulder the burden of the cost of that test.

I'm here sharing my story because I don't think it can be stated enough how much uncertainty transplant patients have to endure. As you've heard for me now, it oftentimes not just one transplant, but two, but three and even four if you are lucky enough to receive the precious gift donation. The noninvasive testing is called a game changer and as I see, it's one of the most important ways that some of the uncertainty of the post-transplant journey can be alleviated for us patients.

It is essential for doctors and patients to be able to work together to set a care path that provides patients with access to the personalized, noninvasive testing regimen that works best for them. Any restrictions on access to these tests not only hinder much needed innovation in this space, but they also have the potential to put transplant patients at risk for rejection. The stakes are just too high to risk any of that.

Thank you for considering my comments today. I will be submitting a written comment, and everyone, have a wonderful day.

Dr. Gary Oakes:
Thank you very much, for taking time to be with us here. Next, on the list of Robert Montgomery MD from NYU Langone Health.

Kari Dupreez:
Dr. Oakes, Dr. Montgomery has not yet joined us, so, if we want the next speaker, we can circle back around and check if he's and later.

Dr. Gary Oakes:
Very good. Let's do that, Dr. Raval. Are you able to join us from Advent Health?

Dr. Nirav Raval:
I am, and a good thing. I'm not going after Bob Montgomery a legend, honestly. So, can everyone hear me having me?

Dr. Gary Oakes:
Yes.

Dr. Nirav Raval:
Wonderful, thank you. Thank you for allowing us, or for me to really get some comments. One of my colleagues earlier, Dr. Teuteberg, who was getting similar comments, but, for the interest of time, I'm going to get started. You know, from a biopsy use, I did catch that a little bit at the tail end of the last presentation, you know, biopsy use is really declining with the use of gene expression profiling and donor derived cell free DNA.

You know, in the heart transplantation, the number one complaint we see post-transplant is, frankly, the biopsy. It can be, you know, obviously be nerve wracking for the patient to go through it, so, many times, et cetera, there are other issues that we'll get into that can be sequala of biopsies as well. You know, we see the incidence of tricuspid valve abnormalities and the way we do this is actually go through the heart through that through the veins and the leg or the neck and go down through there and take pieces of myocardium and you know we do get problems with tricuspid valve and even tricuspid regurgitation. Sometimes, necessitating even surgical fix of the valve, you know, we went through all this trouble to put the heart in, and now we're having to fix the heart because of biopsy.

One other problem that patients really have in our center, which is no different than any others, but we're a high-volume center. Patients really come from obviously the local Orlando area where I am, and up to six hours away, so, you know, that really starts to wear on people to try to travel time, fuel costs, lodging costs, for example, wages lost, because a lot of these patients are back to work and gainfully employed, and so those things, to really start to add up over time and all the while the endomyocardial biopsy for heart transplant, is an imperfect gold standard.

But we still need something to detect rejection that has high sensitivity and high specificity. So, if you get to individual centers like us at Advent Health or other places, schedules are variable all over the place. So, you know, there's not one particular way of taking care of these individuals. Although I did say that probably on average, that is a bit of decline and all centers in terms of the number of biopsies is being done.

Certainly, if you go above two years, it's extremely variable, or not even, not even at all, you, know, codified at centers. And so, you really can't biopsies individuals' forever. But, you know, it's important to surveil these patients even after two years, for example, because of late rejection.

One example might be a simple one might be, non-adherence, patients may get a little complacent in their medication, and, you know, otherwise compliance around that teeter mark, and then actually there's a little bit of an inflection there where we might see some late rejection. But, you know, I'll give you another example another type of rejection antibody immediate rejection starts to increase over that time period as well.

The only way to detect this is via screening. Molecular diagnostic tests, but then also a biopsy at the same time. This is really the only way for us to formulate treatment correctly. We may think it's something else and immunosuppressive in a different way that may cause problems. So, we want to be judicious in what we do and here's an example of where you might use a monthly diagnostic but also a biopsy at the same time in order to correctly treat the patient.

You know, in follow up, if that patient, if you use our example of the antibody rejection, if you treat these individuals in the correct way of, you know, in the follow-up, we may be able to use molecular diagnostic test that we saw from before and see that reduce and that may obviate the biopsy later. So, we may not need to do the endomyocardial biopsy in order to see, hey, that this, this individual, has less graft damage and we are, indeed, treating this patient and we can forgo the invasive biopsy, as I mentioned.

One other area that we've been using it in, in our center is, you know, welcome to Florida. You know, this is a great state where patients will really age well, people age well. I'd say, and we see patients above the age of sixty-five and we transplant these people routinely, and we see patients above the age of seventy and those individuals are a select individual and they ought to do well. But we also know that patient, certainly, but the sixty-five are really going to have problems with the immunosuppression itself, you know, the nephrotoxicity of the medications of course, and also you know, just over immune suppression of the patients, which, you know, we know as patients age, their immune system becomes a little less senescent, or in other words, a bit less active, I would say.

And so, we want to, you know, treat these individuals in a special way. So, we know what is susceptible to side effects and immunosuppression, as I mentioned, and so by using molecular diagnostics, we've been able to reduce some of the immunosuppression levels, and spare kidney function, and other and organ function in these patients, and also, reducing the chance of infection, which is a little bit higher in this, in this population.

Certainly, that's the case above 10 years out, and we still will adjust these patients based on molecular diagnostics. One other good example of using a couple of diagnostics together, is, this is a situation where we use gene expression profiling and donor derived cell free DNA when they have a positive gene expression profiling, but a negative donor derived cellular DNA. What that tells us is that there's not grafting, there's something's going on, right? and what we make, by using both of those, we may be able to figure out that this person may have CMV. So, instead of laughs at this individual we match it look for or CMV.

And in the presence of normal graph function, we may stop the biopsy because we don't need it, we know between those two tests done at one blood, obviously, that this is the case with the patient's graft and the patient's overall health, and we'll treat the CMV rather than the biopsy or immunosuppressing them inappropriately. So, you know, you use biopsy and molecular diagnostics in certain cases, but you also use molecular diagnostics a couple of types of molecular diagnostics together.

In fact, this, you know, in peer reviewed literature, when you use gene specific profiling and donor derived cell free DNA, that actually is the thing that gives us the best sensitivity and specificity for rejection. You know, it's kind of like two plus two equals five, really.

I mean, both are OK, individually, but when you use them together, it's more powerful and more certain, the sensitivity, the specificity is actually better.

So, using them together is something that we clinically do already, frankly, speaking, and to use them individually, I think, is, um, you know, suboptimal for patients and we may be, let down or a different pathway.

In closing, I'd say I disagree with kind of limits on concomitant testing whether it be an endomyocardial biopsy and molecular diagnostics, or even two blood diagnostics at the same time.

I think some good examples here, of where we use them already clinically, you know, we frankly, don't get paid more to do molecular diagnostics, as clinicians, as physicians, we are taught to use data or use testing, only when it's going to change our management. Frankly, speaking, I've got enough stuff to do, and I've got a lot of data coming into me, and my coordinators too, it's a team effort here.

Transplant is a team sport, and the fact is, if we have extraneous data that we're not going to use, I don't want it, because that's data that we're not going to use. It sort of, you know, it gives me more noise than signal, but, frankly, speaking, again, if this is helpful to us, and it is very helpful for the patients, and helps us to better understand how to care for them, as well.

You know, the other issue is, and we, you know, as I was in my medical, you know, medical education, you know, what cost conscious too, frankly, we want to have direct costs that are low as possible and have the best outcomes. I mean, I can't, I don't want to be the most expensive place to get a heart transplant, whether it's Medicare or private payer, and, you know. Furthermore, you know, the value proposition is what we really want here. Quality, over cost, right, if we can improve the value, I think that's what we want to try and do, and this goes for so many different places. in medicine.

As, you know, you know, keeping this in mind, I think it really should be our decision, as physicians, to use to molecular diagnostics together, for the better the patient, or molecular diagnostics in tandem with endomyocardial biopsy because I think that this is something that, that is really clinically driven.

It's out of our data that we've done at the studies, and some of these people are probably on the, on the, on the docket today, for you to speak to you, But I think that this is, this is important, I think, to do otherwise, is really, it's really, sort of a travesty for the patient and will actually reduce our effectiveness in caring for these patients in a value laden manner.

And with that, I'm going to stop my comments there, and I'm happy to take questions, or I'm also really looking forward to getting a written, you know, written there, account of this. I think because I may be able to embellish it a bit more.

Thank you very much for allowing me to give my comments.

Dr. Gary Oakes:
Thank you, Dr. Raval appreciate you taking time to come. join us today.

Dr. Nirav Raval:
My pleasure.

Dr. Gary Oakes:
Next on the list was Dr. Gupta, but I understand he's not going to be able to be with us today.

So, Paul Conway with the American Association of Kidney Patients, are you there, sir?

Paul Conway:
I sure am and I'd like to say thank you very much for the opportunity to appear and to speak to you I wear several different hats.

I serve as the Chair of Policy and Global Affairs, and as a past President with the American Association of Kidney Patients, which is the largest and oldest kidney patient organization in the United States with the highest representation of kidney transplant patients in the US. I also speak to you as a kidney patient for 46 years and one who specifically did three years on dialysis and has lived for 26 years with the gift of life from a young man who was cut down in a car accident but who was selfless in his gift of life to me and it is with him in mind, really, that I speak to you today.

Since I was transplanted in 1997, I've taken over 165,000 pills to maintain immunosuppression into be responsible for my gift of life and I have worked with multiple transplant teams who always encouraged me to take my medicines, being on top of my game, reduce my exposure to infections and in all areas, try to avoid situations where you would have to get a biopsy.

I had two, when I was very young, due to my kidney issues and in one of them, I got sepsis, and I will tell you this a biopsy is not equivalent or substitute for molecular testing. It simply isn't.

The burden on patients of the alternative is terrific, and it's highly impactful upon their families. But what I wanted to raise to you, were a couple of points related to process and pertaining to the changes for clarity, quote unquote of the building article and the deliberation around this.

It was recognized at the outset of this phone call, that it has been controversial and that's true and there's a reason for that because the process was flawed. I have served under four presidents and proudly served under four governors in the State of Virginia. I know, government process quite well. When I was on dialysis, I served as the Deputy Secretary of Health for the Commonwealth of Virginia. I understand what cost control measures are. I understand what it takes to do assessments for utilization, and I also understand what formularies are on the drug side. I know it quite well, and I will say this quite directly.

The use for billing article to articulate and change the practice of policy and medical practice was wrong. Highly wrong, and this recovery period that we're in, which is well meaning and appreciated to get patient comments and other provider comments on the record is important.

Because, as the USFDA shows, patient insight data in lived experience data is evidence on par with studies and peer reviewed journals, and I would encourage you to view the comments today and in the other literature and in newspapers as the same, to get sideways with the American transplant communities, the American transplants societies', the leaders of the top universities in the United States, peer reviewed medical information and to earn yourself a place on the editorial page of The Wall Street Journal. It's pretty hard to do, but it was achieved by a contractor for CMS.

We don't want to assume that the contractor owns all this responsibility, actually. We think it's the appointed leadership of CMS and HHS that owns this problem and needs to fix it.

So, let me lay out a couple of important things here about why you're experiencing such a backlash on this issue.

We completely agree with the comments that had been offered by Dr. Potter of Georgetown, and the American Society of Transplant surgeons and comments that have been offered by other surgeons here in lung, heart, and kidney. But one of the reasons why this is so sideways is this issue of this type of testing came about to address an unmet patient need that we articulated to the federal government and to industry.

These weren't random tests that came about for no reason, they came about to address unmet patient needs. I have been a leader in that field and so what you have here now is at least a decade of the United States Government making it a priority especially in the field of kidney medicine. That transplantation is the preferred policy.

Why? It has better health outcomes for patients. It reduces lifetime dependency on disability payments. People can go back to work and the other thing that it does is, it improves the ability of families to get out of simply the medical mindset and to rejoins society.

Ten years of effort by the United States Government starting in 2013 with HIV to HIV transplant approvals through the US. Congress in 2016, a White House summit on organ transplantation in 2018 the US. Department of Labor, doing special waivers to extend the Family Medical Leave Act for living donors to increase transplantation. 2019 a United States Executive order by the President in the United States capturing the prior six years of effort on transplantation.

The Executive Order on Advancing American Kidney Health Prioritize Transplantation, in 2020 the United States Congress and the White House worked together to extend immunosuppressive drugs suppression, immunosuppressive drugs for the lifetime of the patient if they had insurance interruption and right now, we're on Capitol Hill working diligently to get passage of living donor protections. Why? to increase living donations in the United States. That is bipartisan consensus, policy, prioritization of transplantation.

And the only thing that is different about this national move towards transplant is when you have policies like this that jump up, we call these the government determinants of health, GBH, and for a very good reason.

You've heard the medical experts; you've heard the research experts say why this is so astray from what they see as a new standard and how to manage patients. Patients aren't managed as a class when you have a transplant. Targeted medicine, precision medicine, and the ability of that doctor and the knowledge and skills they have about you as a patient and how they can tailor that through, not just the medicines, but the diagnostics is critically important.

For you to remove that it's not only contrary to policy, it's contrary to patient centered medicine and value-based medicine. It makes absolutely zero sense to us. It is one of the reasons why we have so heavily engaged elected and appointed leaders and the media on this issue.

It is so fundamentally sideways with where this nation has progressed in the past 10 and 20 years on policy, innovation and putting patients first, and I have to tell you it's alarming that something like this can happen absent a process. When the ultimate end users, users of this and the ultimate beneficiaries, the patients, not a medical system, not a medical practice, but the patients are not listened to at the front end of executing policy.

Instead, we're being pulled in on the back end of it, we appreciate it. But that is not patient centered medicine, and this is not consistent with the mission of CMS or the contractors that are charged to support it.

I appreciate you taking the time. I encourage you to strongly look at Dr. Montgomery's presentation. Dr. Potter's presentation and the presentation by the others that are here, but, most importantly, please listen to the patients who have offered their thoughts to you, because their lived experience is legitimate evidence in this discussion and should have been included in the front end. That's the point we've made to the Congress, and we will keep making it. Thank you.

Dr. Gary Oakes:
Mr. Conway. Greatly appreciate your comments.

Dr. Montgomery, have you joined us? Kari, can we tell if he has?

Kari Dupreez:
He has not yet joined us.

Dr. Gary Oakes:
Very well, Let's move on down. calling from USC Are you available?

Dr. DePasquale:
I am.

Dr. Gary Oakes:
Great.

Dr. DePasquale:
Thank you for the opportunity to speak with all of you today on this very important topic.

I do echo the comments of all those who have spoken before me. I'm a transplant cardiologist and the medical director of the Heart Failure and Transplant Program at the University of Southern California.

I've also served as guideline author on the Guidelines Steering Committee for the International Society for Heart and Lung Transplantation, Guidelines for the Care of the Heart Transplant Recipient.

I'm very supportive of the noninvasive tests for rejecting surveillance with gene expression profiling and cell free DNA, particularly their combined use and I have been a principal investigator or on the steering committee on the pivotal studies of OR G-OR and Assure registry.

These innovations have had a profound impact on our patients. At our Center, we reduce the number of biopsies during the first post-transplant year to less than two, or in other words, only one surveillance biopsy.

Any biopsies beyond this point are for cost only, and this is driven by these noninvasive tests. So, the loss of the concomitant approach will really adversely affect our patients.

With this approach, our outcomes and patients' quality of lives are excellent. While eliminating unnecessary biopsy related complications, which are not insignificant, it can harm the new organ and these complications may include tamponade or blood surrounding the heart attacking the heart function, which can be life-threatening, can be damage to the valves of the heart. These are not insignificant complications, although they are rare, you just need one of these to really adversely affect the life of a transplant recipient.

Our targeted approach enhances the yields antimicrobial biopsies as the interpretation of the so-called gold standard, or the antimicrobial biopsy really leaves much to be desired. The pathologists, when it comes to significant rejection agree with themselves less than two thirds of the time. So as the gold standard, it really need some room for improvement, and these noninvasive tests can certainly help.

The non targeted approach can also result in variations in interpretation that can really affect clinical decision making, that can lead to over or under treatment to patients and put them at unnecessary risk. For example, if you have a biopsy where you could go either way, the pathologists may be more likely to call that rejection, leading to unnecessary augmentation and immune suppression and the result of infection and other complications that can come from the incorrect treatments.

And this light, these tests will also enable the personalization of the care transfer recipient to optimize the transplant medications, which may help track the long-term consequences of these therapies, as we have heard most vividly from AB Silverstein, in her New York Times opinion piece, before her untimely passing.

We've also used these tests as a useful tool for our center to extend our ability to care for our heart transfer recipients, far, as we transplant patients who come from Nevada and Hawaii, which are doubling down the road from our center in Los Angeles.

Again, the use of these noninvasive testing commonly enhances the care of heart transplantation. These tests are supported by the heart transplant guidelines and additionally these tests together give a better assessment of the patient's reduce potentially unnecessary invasive testing and potential complications, and the loss of these tests will adversely affect patient care.

I urge Medicare to continue coverage of these tests. I want to thank you for your attention, and happy to answer any questions.

Dr. Gary Oakes:
Thank you, Sir. I don't have any right at the moment, but I appreciate you joining us and sharing your experience and your knowledge with us.

Next up I show Alexandra Harrison Flaxman. Are you available please?

Alexandra Harrison-Flaxman:
Yes, I am. Thank you.

Good afternoon and thank you for allowing me the time to speak today. I am here not just to share my own voice, but on behalf of the entire transplant patient community and particularly, the voices of those patients who do not have the opportunity to be here today.

I feel very fortunate to be speaking alongside such esteemed members of the transplant community, especially the patients, many of which you are, friends and colleagues. As a two-time, kidney transplant recipient and patient advocate for over two decades. I believe the patient voice of powerful and should be present and heard in every room where decisions are being made that impact patient outcomes and access to care.

I was diagnosed with Bardet Syndrome before birth, went through many years, reconstruction surgery, including having one of my native kidney is removed.

Went on dialysis for the first time at only eight and received my first kidney transplant at barely eleven from a deceased donor. Unfortunately, at eighteen, I lost my first transplant. I went back on in-center hemodialysis for almost nine years.

In May of 2013 at twenty-seven I finally received my second gift of life also from a deceased donor, and it's because of access to noninvasive testing that I am in good enough health to be here sharing with you today.

The path to transplant is no easy journey and for some patients it's a journey that they won't even have the opportunity to start. As many of you know, with over 100,000 people currently waiting for an organ transplant in the U.S. today, almost 90,000 of those are specifically waiting for a kidney and sadly, seventeen people will die each day, still waiting for their gift of life, and a new person is added to that waitlist every 10 minutes.

With the National Organ Shortage crisis at an all-time high, now more than ever, for those of us lucky enough to have a transplant, we want to have access to innovations that would allow us to keep our new kidney, heart, or lungs, healthy for as long as possible.

An innovation that not only can detect if there is an issue but can detect it sooner than standard post-transplant testing, allowing for earlier intervention and treatment, and potentially better outcomes. Also, providing a noninvasive option to the alternative invasive biopsy.

I've been fortunate enough to receive the gift of life, not once, but twice and receiving a transplant is precious and we, as patients want to do everything within our power to ensure that that gift is cherished and well taken care of.

In February of 2020, right before the start of the Covid-19 pandemic, I had my first experience with the noninvasive blood test I just moved back to my home transplant center and was re-establishing care and all the rest of my standard labs, like serum creatinine were that were within normal range for me, due to not having been under their care for some time, they also wanted to perform a biopsy.

This terrified me because of my previous experiences with biopsies. I had a biopsy done when I was younger, and they accidentally nicked an artery causing me to bleed uncontrollably for almost three days. My parents were told I was losing too much blood and needed transfusion, while hospital staff rotated, holding bricks wrapped and towels on my abdomen, trying to stop the bleeding.

Since then, the thought of biopsies gives me anxiety and PTSD to the point that I must be fully sedated in order to have one. At the time that my team wanted to do another biopsy, I was aware of the fact that there were noninvasive options we can use. I advocated for this, and my team ordered an AlloSure to get a full picture of the health of my kidney.

A few days later, I got a call from my coordinator letting me know that my AlloSure score had come back at two zero point seven signaling that I was in fact experiencing some sort of injury and more testing with later confirm antibody mediate rejection. Mind you, the rest of my labs were still within range for me.

My team quickly went into action putting together treatment plan, starting me on multiple infusion therapies to help stabilize the ABMR. three months later, AlloSure was performed showing, I'd come down to 2.3.

It wouldn't be for two more months, but my crowd then would finally start to reflect that something was wrong. Now, this might not seem like a significant amount of time to you, but as a two-time kidney transplant recipient who lost her first kidney at seven years and 10 months, this was my greatest fear to lose my kidney around the same timeline that I was months from celebrating seven years of my current transplant.

Over the next nine months of infusion therapy and immunosuppressant changes, my AlloSure would come down to zero point six and while the damage had already been done and I had entered into rejection, because of my team having the opportunity to act quickly, they were able to stabilize me with the last three years, keeping me off dialysis and working towards a preemptive living donor transplant.

I like to use the analogy of a house on fire. AlloSure, being a smoke alarm, saying, hey, something is wrong, but it's not too late to try and fix that and even though the damage could not be reversed because of AlloSure, I only lost a room and not the whole house.

Because of access to noninvasive molecular diagnostic testing, I celebrated 10 years on May 18th of this year, and while I am now on the road to my third transplant, I could be in much worse shape than I am now.

Only last week I found out that my husband has been approved moving forward as my non direct living donor and I want to be sure that has donation which will lead to me getting my new kidney is not done in vain.

I am already fearful of what the future may bring and whether I have access to noninvasive testing shouldn't have to be a part of that.

I share my story with you to demonstrate how much we as recipients go through to protect our gift of life, a gift that was given so selflessly and deserves to be honored.

Transplant patients need and deserve access to innovation in a space that has seen so little over the last several decades. It's important that transplant patients and their care teams be able to make informed decisions about their care without the worry of coverage. What is best for a patient and their transplant is a decision that should be made between the patient and their care team. Every transplant patient is unique and deserves individualized care and treatment.

The proposed changes to coverage of noninvasive testing would be detrimental to the transplant community, not only impacting patients and their transplants but also living donors and donor families who have given the gift of life. This could also stifle future advancements that could be coming down the pipeline, limiting feature innovation for our community.

I hope that you all consider all the remarks you've heard today. I will also be submitting a written comment. Thank you for your time.

Dr. Gary Oakes:
Thank you very much for taking time to come join us and share your experiences.

Next up is Eddie Garcia.

Eddie Garcia:
Yes, thank you. OK, good afternoon, my name is Eddie Garcia.

Thank you for the time to share my thoughts on the March 2023 billing article regarding molecular testing for solid organ Allograft rejection.

I received a heart transplant on April 16th, 2020. During the summer of 2021, the noninvasive post-transplant test most likely saved my life. At a minimum, it saved me from pain, suffering, an additional financial stress.

My Heart Failure Journey started on June seventh, 2010. That day, a 100% occlusion in my left anterior descending artery, otherwise known as the widow maker, caused a massive heart attack. I was 46 years old. My wife and I had two young daughters, and my career was on the rise. Ten days later, cardiac arrest causing my heart to stop beating and a rare form of lung failure required me to be on life support in the ICU.

My medical record on June 28th, 2010, simply stated that I was, quote, "Intubated, sedated and paralyzed". I remained in that state for six weeks as doctors worked on my lungs. When I emerged from a medically induced coma and survived the lung failure, I still had a damaged heart. For the next 10 years, I managed congestive heart failure with a strict diet, exercise, and medicine enrichment. My heart transplant in 2020 gave me a new lease on life.

A critical part of my post-transplant management plan included noninvasive post-transplant tests for surveillance purposes, as opposed to invasive expensive, and as we've heard traumatizing biopsies. The testing process was simple. A phlebotomist came to my home to do a standard blood draw. Within three days of each test, I had the results. For the first one post-transplant, my doctors call to confirm thar that there were no signs of rejection, always well.

In late June 2021, fifteen months post-transplant, the noninvasive test, detect that my body was rejecting my heart. I had just completed a daily three mile walk with my doctor called. I had no symptoms of rejection. Nonetheless, her direction was urgent and to the point, I checked into the hospital that day to undergo eleven days of treatments to address rejection. In the hospital, doctors administered plasmapheresis treatments.

It's a process that removes blood plasma from the body, separates it into plasma cells, and transfused sales back into the bloodstream to remove antibodies that cause or organ rejection.

After this, the eleven-day treatment, in six monthly outpatient treatments, my body was free of antibodies that were attacking my heart with minimal allograft damage.

The short story here is that the noninvasive post-transplant test works. It's the proverbial canary in a coal mine. The noninvasive test is effective, efficient, and it saves lives and money.

Without reservation, I urge you and Medicare to continue covering noninvasive post-transplant testing, as was done pre-March 2023.

On another note, the proposed coverage for these tests, as stated in the March 2023 billing article, is too restrictive. Limiting patient access to these tools for surveillance purposes and requiring patients to exhibit some sort of rejection before being able to use these tests is both costly and mostly draining and usually too late to save lives.

Under the March 2023 order, I would not have had access to that test and that detected my rejection in 2021. On that note, there's a good chance I wouldn't be here today testifying before you.

Transplant surgery is a significant, emotional, and financial investment for patients, families, and insurance providers, not to mention doctors. Regular, noninvasive post-transplant tests for surveillance purposes effectively and efficiently preserve the investment for all involved.

The March 2023 billing article just doesn't make sense. It's my heartfelt hope, my new heart, heartfelt hope that you and Medicare reconsider the decision regarding the March 2023 billing article.

Once again, thanks for the opportunity to share my thoughts.

Dr. Gary Oakes:
Thank you so much. Appreciate it.

Next up is Tiffany Jones Smith from the State of Texas Kidney Foundation.

Tiffany Jones Smith:
I'm honored to represent the Texas Kidney Foundation. Our mission is clear to slow or stop the progression of kidney disease. Through genuine commitment and mutual respect. We have built a community engagement model and we have earned us the honor of a trusted agent.

We approach our mission and our position or community with humility. What brought us to this juncture? Our unwavering, unwavering belief in the intrinsic value of every individual and our commitment to treating each person with the dignity they inherently possess.

Our strategies are rooted in every space scientific paradigm with our community empowerment model serving as a lynchpin for all our initiatives.

Across Texas, we are not we are recognized, not merely as a resource, but as a beacon of hope, particularly for the underserved. Numerous churches, synagogues, mosques, and community centers place their trust in us relying on our expertise and commitment.

Through our endeavors, we offer free early detection test, vital education, and a pathway to preventative care. We open the lines of communication between patients and practitioners.

We serve as an example of what can be accomplished when curiosity, mission and commitment align.

As President and CEO of the Texas Kidney Foundation, I've dedicated my life to championing the rights and needs of kidney transplant recipients across the great state of Texas. Supporting early detection measures and connecting patients to the many options that exist within the transplant world that are part of our mission.

My journey into this realm was not by choice, but by private personal circumstance. I lived the loss of fifteen beloved family members to kidney disease.

As I delve deeper to understand the silent killer behind this heart wrenching loss, I discovered it was genetic variant named APOL1, for which I carry [inaudible].

I quickly began to learn all that occurred about the genetic variant. Today, well, abreast of what's going on with APOL1 and a published author for the Journal of American Society of Nephrology on a paper called Diagnosed Education and Care of Patients with APOL1.

I hold the conviction that those nearest to the issue are also nearest to the solution. APOL1 is not merely the scientific fact for me, it is the fuel to stoke the fire in my belly because it is a ticking clock. A stark reminder that the very disease could manifest itself rapidly within me, just as in my brother in 2019 resulting in receiving a preemptive transplant.

Three of my cherished family members have been blessed with transplants. Where, once the narrative was one of unending waiting of lives fading away on dialysis. We now see a narrative or renewal of second chances.

Noninvasive molecular diagnostic tests are not merely medical tools. They are the lifeline that assists my brother's care team and my two cousins' care. All are high-risk patients and all are healthy because of the gift of life being monitored by molecular diagnostic tests.

Today, I'm here asserting the pressing need for unrestricted, patient access to noninvasive molecular diagnostic tests. Our kidney transplant beneficiaries under the guidance of their provider recognize these tests are essential components of their regular healthcare.

With precision medicine in play, we know that each patient is an individual, they have to be seen as individuals and not as a singular class, not regulated by policy. Health care should never be regulated by policy.

Undergoing a biopsy is not just physically taxing. It demands travel, logistical efforts, breaks from work, or caregiving roles. These challenges are notably magnified for our economically underserved number.

While the journey to achieve equitable access to care for marginalized black and brown communities is still in its early stages. Trust is a vital component for transparent patient practitioner dialog is jeopardized when choices are made to restrict access to noninvasive tests in favor of costlier invasive alternatives. Transparency in policy making is important.

Let's be clear, for our kidney transplant community, the repercussions of losing a transplant beyond financial considerations, it is an emotional upheaval marking a return to the demand and regimen of dialysis. As you heard, previous advocates state is really traumatizing to have a biopsy.

The simplicity of noninvasive diagnostic test, a straightforward blood draw, possible within the confines of one's home, ensures no patient facing barriers in accessing their rightful care, ensuring uninterrupted care is the bedrock for successful transplant and overall patient well-being.

I earnestly urge you, as you weigh the coverage for molecular diagnostic test under the proposed LCD, to deeply consider my remarks. As a representative of a trusted agency, I emphasize the paramount importance of ensuring all kidney transplant patients along with the wider transplant community, have unrestricted access under their physician's guidance, for the tests that are pivotal in preserving the invaluable gift of life they have acquired through transplantation.

The trust our agency has built, stands testament for the gravity of our advocacy. Your attention and thoughtful consideration today is deeply appreciated.

Dr. Gary Oakes:
Thank you, very much appreciate it.

Next up is Melissa McQueen with Transplant Families.

Melissa McQueen:
Thank you so much for the opportunity to speak today. I will not reiterate the wonderful cometary already made, but I will briefly share my experience.

My name is Melissa McLean and the president of Transplant Families, a collaborative group that supports a pediatric transplant community and their families. What brought me to transplant was the birth of my youngest son, Dylan.

He was born with cardiomyopathy and subsequently needed a transplant. He received his gift of life at eight months old. We didn't have a transplant center near us when we needed it. So, we traveled for care. Much of the traveling we did, for the first two years of his life, was necessary for biopsies. He had dozens of biopsies within that time period. This is common for many recipient children.

As a now 15-year-old, he has had a lifetime of biopsies reminding him that you will forever be a patient with all the side effects that go with that including but not limiting, limited to missing schooltime, extreme difficulty with anesthesia, inpatient stays and intense anxiety.

The first time my son had access to cell free DNA test, he was thrilled that he wouldn't have to be bedridden for days on end, and he could finally participate in his state wrestling tournament, which he placed top for it.

As president of Transplant Families, I can attest that there is no topic spoken about more by families than biopsies. This is a constant source of anxiety for them. We urge you to reconsider restrictions to noninvasive testing.

Invasive biopsies are disruptive to children's lives and traumatizing to their psyches. Children already have difficult access points and have so many invasive tests being transplant recipients.

Many of these happen in their first year alone. Many families have to travel for the spouses as well, bringing an unnecessary burden for those in rural areas. This is not equitable for families that can't afford these tests, which wrack up quickly to the tens of thousands of dollars each time.

Please consider giving access to cell free DNA test to help give these children a more normal childhood that they deserve and that their donor families intended.

Thank you so much for allowing me to speak today.

Dr. Gary Oakes:
Thank you for taking time to do so.

Last on the list per day that I show is Bill Ryan with transplant by Foundation.

Bill Ryan:
Yeah, Hi. Good afternoon.

I'm President and CEO of the Transplant Light Foundation, a 501C3 non-profit representing almost ten thousand transplant recipients and caregivers in the United States.

Along with producing the biennial transplant Games of America, we also publish Transplantation Magazine. It's a full feature publication dedicated to the transplant community.

Our mission in supporting the transplant community has been directly affected by that recent decision to restrict access to noninvasive post-transplant testing that provides early diagnosis of transplanted organ failure.

I'm here today to provide commentary on behalf of thousands of recipients and their families, who view these changes as a step backwards in the care and treatment of transplant patients nationwide.

Post-transplant patient care takes a significant toll on recipients and their families. Noninvasive testing provides a measure of relief at the same time, critical diagnostic tool for their medical teams. These tests provide an early warning system that suggest treatment options for organ preservation before significant rejection can occur.

Without the capability of early analysis, there's possibility of the organ may go into failure, resulting in either more intense treatment options are ultimately complete organ failure.

The development of noninvasive post-transplant testing has been one of the most dramatic improvements for patient care in our community.

The decision to restrict or reduce coverage for noninvasive testing is the wrong message to send to companies who are seeking to design and implement new and innovative medical care for transplant patients.

The alternatives to testing, is the use of biopsies for analysis of organ damage. Biopsies are invasive, an invasive option that requires a surgical procedure. Aside from the invasive nature of the biopsies, the patient, and caregivers require time off of work for the procedure and enter unnecessary burden of increased travel related costs and extended recovery timeframes.

These challenges often come with the loss of wages along with those travel costs, these issues are exacerbated by our economically disadvantaged patients with and within our rural communities.

We're here today to advise the patient community needs these diagnostic tools in order to maximize the health benefits that were provided in saving the gift of a transplanted organ. Our patients deserve better, and, on behalf of the thousands of patients and caregivers, will also be submitted comments later this week.

Thank you for listening.

Dr. Gary Oakes:
Thank you, Mr. Ryan, any closing remarks before we end this session, please? Hearing none, please accept our gratitude for coming out. Taking your valuable time to share experiences and to share knowledge. We will take these comments very seriously, they will all be published along with the policies and with the billing and coding article and we will have responses to those that require a response. Anyone may submit written comments going forward until the 45 days ends, and I'm going to turn that back to our admin team to help me with that date.

Kari Dupreez:
All right, thank you, Dr. Oakes. In closing, we would like to communicate the next steps and the policy development process.

The comment period for the proposed LCD will remain open until September 23rd, 2023. All comments to be considered by our medical directors for the proposed LCD must be submitted in writing.

Written comments can be e-mailed to policydraft@noridian.com or mailed to the address on your screen.

Comment Information for our proposed LCD is located on our website at Noridianmedicare.com.

Upon review of the comments, our medical directors will either finalize or retire the proposed LCD. Responses to comments will be available in the Response to Comments article.

Please monitor our website or register for listserv notifications to be informed of actions taken on our proposed LCD.

And, with that Dr. Oakes do you have anything else you'd like to say before we end the meeting today?

Dr. Gary Oakes:
I do not, just, again, thanks for each of you coming out and share, time with us.

Hope you have a good afternoon.

Kari Dupreez:
All right. Yes, thank you. This concludes our meeting and thank you for attending Noridian Open Public Meeting today.