MolDX Open Public Meeting - June 24, 2021 - JE Part B

JOCELYN FERNANDEZ:
OK, let's begin our meeting.

As we know, your time is valuable. Good afternoon and welcome members of the public to the MolDX open meeting.

There will be four proposed LCDs presented for comments and they are MOLDX Melanoma Risk Stratification Molecular Testing.DL37750 for Jurisdiction E and DL37748 for Jurisdiction F.

MolDX Biomarkers for Risk Stratify Patients at Increased Risk for Prostate Cancer DL39005 for Jurisdiction E and DL39007 for Jurisdiction F.

MolDX Multiplex Nucleic Acid Amplification Test Panels for Infectious Disease Testing DL39001 for Jurisdiction E, and DL39003 for Jurisdiction F.

MolDX Next Generation Sequencing Lab Developed Tests for Inherited Cancer Syndromes. DL 38972 for Jurisdiction E, and DL38974 for Jurisdiction F.

The meeting will be recorded. The audio recording and written transcript will be posted on our website within 30 days from today's meeting.

All lines are currently being muted and will remain muted throughout the meeting. Only registered presenters will be allowed to present their comments during the meeting.

For the presenters, each of you are being allotted 15 minutes to make comments. 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 when called upon and will hear the moderators voice when one minute remains.

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. We ask that any comments made today also be submitted in writing, and while only registered speakers will be commenting today, anyone in attendance may submit written comments.

I will now turn the meeting over to Dr. Larry Clark for his comments. Dr. Clark

DR. LARRY CLARK:
Thanks Jocelyn, and thanks to you, Rachel and everybody that put this together as usual. My name is Larry Clark. I am one of the Noridian Medical Directors. I'm going to be joined today by Dr. Anitra Graves colleague and fellow CMD. Dr. Graves brings a background of active clinical practice in pulmonary medicine and critical care medicine. In addition, she has specific and additional expertise and training in the analysis and review of evidence of an evidentiary basis and you will see her handiwork in some of our upcoming policies.

She's also coming over from another meeting and so I realized a number of you are so, we are going to go, Jocelyn said, we are going to be time effective and get down to the discussions.

For the policies that we do not have discussions for today, they may be coming to subsequent open meetings and I do know that we have circulated the prostate biomarkers and NGS for inherited cancer syndromes to our usual assortment of cancer treating associations and also, in this case, infectious disease for the NAATs.

So, please come back and take a look, as we will be getting written commentary from the appropriate societies. And so, welcome to all of you. Thank you for coming back for another open meeting with us. I think we're going to have some interesting discussions today based upon the slides that we have received. So, with that, I'm going to go right back to Jocelyn, if you would take over and introduce our first presentation.

JOCELYN FERNANDEZ:
Thank you, Dr. Clark, For the first proposed LCD as MolDX Biomarkers to Risk Stratify Patients at Increased Risk for Prostate Cancer.

There are no public, or there are no registered public commenters, but I would like the record to reflect that this proposed LCD was presented during an open meeting. Written comments will be accepted until July 3rd, 2021.

The second proposed LCD is MolDX. Next Generation Sequencing Lab Developed Tests for Inherited Cancer Syndromes. Again, there are no registered public commenters, and we would like the records to reflect that this proposed LCD was presented during an open meeting. Written comments will be accepted until July 3rd, 2021.

The third, LCD presented for comments as MolDX, Melanoma Risk Stratification Molecular Testing. The first commenter is Doctor John Vetto.

Dr. Vetto, your line is open.

DR. JOHN VETTO:
Can you hear me now?

JOCELYN FERNANDEZ:
Yes, I can.

DR. JOHN VETTO:
Well, thank you very much. I want to, I want to thank Noridian for allowing me to speak today I am Dr. Vetto of the Oregon Health Sciences University in Portland, Oregon.

I'm the Clinical Director of the multi-disciplinary Melanoma Program here.

I do, I will just close that I'm on the Speaker's Burea for Castle. I'm not being compensated to appear today.

I'm here as an interested clinician, who uses this test extensively and like it.

I am also, I'll be presenting a paper that we recently published on, the test, it was an independent study, was also not supported in, anyway, and represents our independent data here at Oregon on this test.

Next.

So, as I've already said, we have an extensive experience with this test.

The, we believe that this test at 31 GEP, and again, all my comments will be unbranded, it, informs important management decisions both before and after sentinel lymph node biopsy.

And I want to divide my comments today into the two major uses for the test, first, is to identify subsets of patients with very low risk of a positive sentinel node and to guide discussions between the clinician and the patient regarding whether we should be doing sentinel node biopsy in their individual case. Secondly, it informs surveillance opportunities for patients whether they've had to sentinel node or not, and for stages 1, 2, and three.

This is a quote from our paper, again, I'll be referring to this paper throughout the talk.

This paper, first author, as Sam Arnot, was a fellow in our lab, but it is it is a summary of the data and use of the test here at OHSU.

And the quote is 31 gene GEP, as prognostic information in the evaluation of primary continuous melanoma.

It should be considered in patients refer to central node biopsy and remember, I run a large multi-disciplinary melanoma program sees melanoma at all levels, and most of the patients that are coming to us are coming to us for potential surgical staging and management.

Next.

So, the Knight Cancer Institute here at OHSU is an NCI designated cancer center and we lead a large, tertiary interdisciplinary melanoma program that serves the entire northwest except for the area caught by the University of Washington. So, our catchment area is very, very large and I'll be stressing that later.

I'll also be stressing that the GEP test that we're talking about does not replace sentinel node. It augments staging.

It does not replace staging. It's really to me as additional information that can be quite helpful.

And that's where I take exception with some of the other published studies where they actually seem to think that these tests are exclusive and they're absolutely not and I'll show that. Regarding to the Grossman and Marchetti articles, they, they, they do make that assumption that these tests are exclusive and they're not, they should be used in concert with each other.

I'll demonstrate that and also, they don't really doesn't address the use of the tests for sentinel node guidance and interestingly, the Marchetti article actually concluded that the test was useful for low risk, stage two patients, and high-risk stage one patients. And as you'll see in the second part of my talk, that's exactly our point, that's exactly what we found. But because they're not clinicians who use the test and follow all breadths of melanoma, they didn't really pick up on the importance of that. So, I'll stress that today. I think it's important for Noridian to hear from clinicians, like myself who not only know the data, but integrated into our practice.

Next.

So, let's go ahead. I'm going to divide the talk into two broad categories of use first is sentinel node optimization.

Next.

So, this table, for the non-surgeons in the crowd, the NCCN tells surgical oncologists to perform or not perform sentinel node biopsy based on percent likelihood that the sentinel node, it'll be positive.

If it's less than 5%, don't do it if it's greater than 10%, do it. The trouble is the NCCN doesn't tell you how to know that, now the SSO has come up with the left side of the table, which are broad links between stage and risk. But there's no data for that that was basically made up. It's what most surgical oncologists do in the country. But when you do that, you end up with sentinel node positivity rates of 11 or 12% meaning that the vast majority of patients who have a sentinel node biopsy. We don't really learn anything.

And that's important in the Medicare population where there may be comorbidities and going into the operating room. That's not a small thing.

Next.

So, what we did here in Oregon was we looked at 1400 patients collected from around the country who had the test and the sentinel node biopsy. and we looked at an analysis, looking into Medicare population of patients older than 65. We looked at 1400 patients, we called out 448 who are Medicare population, and we, and we discovered a clear link between the test result and the likelihood to sentinel node be positive. So, if the, if the test shows Class one A, which is the lowest risk score, the chance for positive sentinel node mean risk was 1.6%, well below the NCCN guideline of 5%.

Conversely, if the test is classed 2B a highest risk, and you're well above the 10% cutoff, and sentinel node should be offered, and the intermediate scores correlated with intermediate risk.

Now, this is important, because in the Medicare population, most patients, about 80%, will be in that blue box.

So, when we looked at the data and did an analysis of what the percent likelihood of a positive sentinel node would be, if we utilize the test and excluded patients who didn't really weren't going to learn anything from the sentinel node biopsy, the positive sentinel node rate went from 11% to 23%.

So, we can enrich the sentinel node. I'm not recommending doing less sentinel node.

I'm recommending doing it smarter and avoiding the morbidity of surgery in patients who don't need it.

Conversely, we can also call out patients who may have comorbidities, but they actually are at a higher risk for a positive sentinel node above NCCN cutoff and if those patients do not have the, shouldn't have too many comorbidities and we don't want to go to the OR necessarily, we can do watchful waiting per the MS: T2 guidelines, which is basically scanning and ultrasound scanning and exams, and then operate only, if they proved to be in that 11.9% clinically.

Next.

So, this is why we've done to Oregon, since we've adopted the test.

Patients with Medicare, age present to us, stages 1, 2, or stages T1 T2. This two mm or less. That's what this data was confined to. And then, if they are Class 1A, we can sit them down and say, Look, we don't necessarily need to do the sentinel node, we have the patients and our registrar study. They sign a consent saying, they understand, and they agree, and they want to avoid the OR.

On the other hand, if they're intermediate or high risk, we can discuss an off of the sentinel node, based on the numbers I showed you on the previous slide, and if they're not suitable candidates for the OR, we can do watchful waiting surveillance with ultrasound and exams. Like I said, the vast majority of patients will be in the blue line and that will enrich our sentinel node findings.

Next.

So, let's go on to the second utility, which is management, follow up decisions.

And again, this was alluded to by the Marchetti paper, but I don't think they picked up, and how important and useful this is

Next.

So, this is our paper, this is the Sam Arnot paper, I'm the senior author on this paper. Get an independent study unsupported. This is an event, this is our multi varied analysis from that paper looking at TP score sentinel node, outcomes, and stage and what we found out, there's an all patients, but all stages at all ages, class one, and class 2B, that's the lowest risk and the highest risk ,were significantly associated with very different rates of sentinel node positivity. I alluded to that on the previous slide and importantly, patients with low-risk class 1 results and a threefold lower risk of any recurrence, compared even to patients with a negative sentinel node.

So, I think this is a powerful predictor this is the (unrecognizable) and paradigm of cancer, this is the thinking and patients with melanoma can fail in the nodes. They can fail, in the distantly, I think, sentinel node, it's a very good way to measure of viscous of nodal risk if we think it's high enough to do it and this test is a better and significantly, valuable way to look at distant risk.

So that's why I think that's falling out this way in our study, within patients who had a negative sentinel node, and were considered to be low risk, but had a class 2B results. So, in other words, the AJC said they were low risk patients, stages 1 and 2A. If they had a class 2B result, they were eight times more likely to have a recurrence and then if they had a 1A result.

Next.

This is a bar graph on our paper. So, on the far left, at the double negatives and, again, I'm stressing that we're using both tests. We're using staging, we're using, GP Score, because I think staging is a good reflection of nodal failure. GP score is a good reflection of distant failure and there's obviously some overlap as I showed you previously. So, on the far left of the double negatives, where they're both risks are negative, those are the patients that we can discharge from our high-risk clinic.

These are patients who are traveling hundreds of miles to see us sometimes and we can actually discharge them and do follow up only there is cured as we can get them. On the other hand, are the double positives. These patients stay in our high risk clinic, they go on clinical trials, we follow them very closely, but interesting are the immediate bars, patients have discord in results, so either low risk by genetic score, percentile node positive and we know there are sentinel node patients that we cure with central node biopsy, because all they ever had as a sentinel node was uh a nodule metastatic potential, they didn't have a distant potential, and there are patients in the third bar who conversely are sentinel node negative they don't have a nodal metastatic potential. But they have a high risk for distant failure, and they are interestingly, these groups are of intermediate risk and you can see that actually they are having the higher GEP scores actually puts you at higher risk for relapse, like you'd expect.

Next.

So, back to our, this data, this is sentinel node data, we've all seen these graphs on the MSLT1 trial these are graphs of patients who had a negative sentinel node and if you look at relapse free survival or distant metastasis survival, we know that even though the sentinel node is negative, the patients continue to relapse and die.

And why? Because they had a distance metastasis phenotype, even though they didn't have a nodal metastatic phenotype.

So, what we do with these patients, we have determined they don't have a nodal metastatic phenotype, but we run the test and when you run the test you can see.

Next.

That you can separate out kind of the wheat from the chaff here.

There's the blue line of the double negatives. I want to focus on the distant metastasis survival graph, which is what patients care about, the top blue line and the double negative patients I showed you in the previous bar graph.

Those patients, we can discharge them from our high-risk clinic, whereas the red line, we hang on to those patients. Now, those patients have the highest genetic risk. It's not a death sense. They’re relapse rates are still below 40% and that was brought out by the Marchetti article, but to us, or identifying so-called low risk patients who have a higher risk of relapse and we follow those patients.

What we're doing in Oregon is we're transferring our follow-up resources from the blue line, to the red line. There's a lot more patients on the blue line then red line. So, we've done an economic analysis and it's pretty much a wash.

So, we're not spending more money, we're just spending it smarter and we're getting patients out of the clinics who need who can go into that staying in the clinic if they need to stay there.

Next.

This is from my meta-analysis again, and this meta-analysis I made these points, GEP was independently predictive of relapse and so-called low risk patients.

I'll show you that again the minute.

A GEP class to 2B is all that's the highest with significant independent predictor of relapse and ...distant metastasis. in addition, to high-risk staging it, as defined by stages 3B at, excuse me, 2B in 3 and 31 GEP, should we concluded that the 31 GEP should be used in conjunction with AJCC Staging to identify patients who are at higher risk of relapse, so that we can do more intense follow up in the right population and let the other patients go.

Next.

This is a study that we did with Brian Gastman at the Cleveland Clinic, myself and Dr.Leachman, here in Oregon.

We looked at the first 690 patients who had the test run, and we knew, no outcomes were known, and we're looking just at NCCN low risk patients here.

And again, the double negatives are on the blue line. The more risk patients with higher scores are at the red line.

So, yes, we can look using this test and so-called low risk patients and find the patients who are at higher risk of relapse and follow those patients more closely.

We have and we are in the process of designing a south-west oncology group study to look at these patients prospectively randomizing them to get or not get higher follow up, higher level follow-up per NCCN guidelines, which would be every six months CAT-scanning.

Next.

So, here's what we're doing in Oregon. We stage the patients at the AJCC low risk and genetic score's low risk. Those are the double negatives, they are leaving our high-risk clinic, that's the top blue bar. Conversely, if they are low risk, but have high risk genes were following those patients, again, transferring resources from the top blue bar to the middle red bar, at the very bottom are the double positive patients.

An interesting group is that third blue bar where there's discordance, the staging is high, but the genetic risk is low, can we decrease in tendency in those patients? I think that's a good target down the road for a randomized study, but a question to be answered for the future.

Next.

Oh, I should mention on that last slide, can we go back for a second? I should mention for my last slide that since we adopted this strategy, the first six months we adopted it, we saved, 330 follow-up visits by transferring, follow up from the top blue, to middle red and there was tumor registry like data and there were no relapses in that data.

Next.

So, to sum up, I'm sorry. Next, so to sum up what I've discussed today, are potential use of the tests, first of all, to guide sentinel node biopsy. Particularly in Medicare patients where we can identify large group of patients with a very low risk of a positive sentinel node and avoid that morbidity in that, in that population, while identifying the patients who have a higher risk offering sentinel node to them or follow up if they don't have if we'd like to still avoid the OR. We can identify double negative patients who are going to be discharged from high-risk clinics and then we can identify AJCC, low risk patients, who are actually at higher risk and transfer resource resources for follow up, from that second bullet group to that third bullet group. I did not have time to discuss the fourth indication, we're doing here in Oregon, which is to look at the subsets of IIIA patients. As the audience may know, IIIA patients are indicated by the FDA for immunotherapy but were excluded from the federal trial. So, there's no data to, tell medical oncologist whether the treat of IIIA, a patient or not. A IIIA patient has a good risk patient who has micro metastatic disease in their sentinel node. So, the question in IIIA is that we carry them with a sentinel node, or do they have a higher distant failure rate, and should they also get immunotherapy. Right now, that's being done by geography which and, and bias institutional bias, which is wrong. So, we're, we run the tests, and show the data to the medical oncologists to discuss it into two parts.

I want to recommend moving forward for the LCD that Noridian consider our paper from Sam Arnot, first author, myself, senior author, and Eddie Hsueh’s recent paper from JCO Precision Oncology.

Thank you very much.

DR. LARRY CLARK:
Thank you. Can I ask you a question? I mean, it was that was very interesting presentation. I appreciate the fact that A, you did an independent study and B, the called out distinct Medicare beneficiaries it is a separate group in some ways.

So, thanks for doing that. Is your technical message that there really are nodal versus distance failure phenotypes. I mean, is that really the bottom line to what you said today?

DR. JOHN VETTO:
I think that is a bottom line.

If you look what's happened in breast cancer in the last couple of decades, they moved from how steady I'm thinking, we're put lymph nodes in the center of care, into a thinking where we realize that tumor or it can do anything it wants. You can go to the nodes if it has the right thing if it has the right genotype, it can go to the body, and that's why women with no negative breast cancer had been offered for some time now, chemotherapy because we know they'll fail even if they don't have a nodal metastatic phenotype.

Now pivotal to that was another GDP. GPs in breast as you know are about 10, at least 10, if not 15 years ahead of GPs in melanoma but I think there's GP is a great start. I think people across the country are starting to think of melanoma in a non-steady way, where sentinel nodes are predictive but not the permanent. Not statistically significantly related to melanomas specific survival, that was shown in the MSLT1 Trial. It puzzled a lot of dermatologists who think well, it's either sentinel node or not, but to me, it's not. It's look at the patient individually. Do they have a nodal menaced phenotype? I can figure that out as a surgeon with a sentinel node biopsy if I think it's indicated and I'm using this just to drill down into what that means, then look at their distant phenotype is really what causes morbidity and mortality.

What is that? And sentinel node is only a surrogate for that. To that we need something better, biologic, genetic. I like this test whether it be future test (unrecognizable)

But I think it's a very exciting beginning to introducing genetic testing and non Haltstedian thinking into melanoma.

Dr. LARRY CLARK:
That non-Halstedian thinking. That's an interesting concept.

Can I ask one more question? When you think about sequencing for melanoma, I think that number is now knowing that, you know, like this BRAF Variants and NRAF and stuff.

How does that how does that sequencing fit with identifying these distinct phenotypes? Or does it do it at all?

DR. JOHN VETTO:
No. I think it does.

I have to say that this is a little this test is. It gets a little more granular than that.

This is a 31 gene test.

BRAF is actually not in there because BRAF is more of a drug response genes. I don't I didn't have time to show you the signature. The signature was developed by Pedram Germai at North-western in Chicago.

And what it does is Pedram went to the literature and found genes that really predict for badness, independent of sequence subtypes and he came up with what I think is a really interesting signature.

And these are genes that predict for angiogenesis, lots of gap junctions, lots of cellular adhesion, the things that really push metastatic advanced, both nodal and distal, and just as I showed you, there's some overlap between those two phenotypes.

But I'm not enough of a geneticist to comment on that, maybe Dr. Goldberg can, but I don’t want to put him in the hot seat, but I don't I'm not enough a scientist to comment on that, but I do know it's a very useful signature.

DR. LARRY CLARK:
Well, thank you. OK, that was really excellent. I want to ask Dr. Graves. Have you been able to join us yet? And do you have any questions?

DR. ANITRA GRAVES:
Ah, yes, I have been able to join, I just had one question and wanted Dr. Golberg, comments or not Dr. Golberg , I wanted comment on, what frequency of testing you would recommend for these patients?

DR. JOHN VETTO:
Well, there's just a once a time test.

You get it on the primary, you need to do it on the buy original biopsy, because that in melanoma is you know that that often contains the most tumor because the majority of sentinel nodes are negative and 75% of (unrecognizable) are negative.

So, we do it on the primary, usually the first biopsy is done once, and it's considered because it's a measure of the primary's genetic signature.

DR. ANITRA GRAVES:
So, no additional testing if you have subsequent development of disease, and a node or so forth you would not need additional testing at that point, Correct?

DR. JOHN VETTO:
No, that's correct.

You can certainly test those for mutations to drive drug testing, drug selection, and that's being done by foundation testing. As you know, at most medical schools, we do it here in Oregon. We do our own foundation testing to see where the tumors going, in terms of mutations and possible drug targets.

But this is more, this test is done at the outset to drive risk stratification. So, for initial planning of a patient's care.

Now, if that, you know, that the tests will predict the patient's risk for failure, if the patient then fails, then you need to follow that patient’s clinical course, and their tumor targets for drugs, and that we do within house. Mutation panel test thing you're looking at BRAF and NRAF and seek it, of course. And we also do foundation testing for patients with more advanced disease, but that's not related to this test.

DR. ANITRA GRAVES:
Thank you very much. Appreciate it.

DR. JOHN VETTO:
Thank you.

DR. LARRY CLARK:
Jocelyn if you would bring out our next speaker, please.

JOCELYN FERNANDEZ:
All right. Thank you Dr. Vetto for your comments. The next commenter is Dr. Matthew Goldberg.

Dr. Goldberg, your line is open.

DR. MATTHEW GOLDBERG:
Thank you. Can you, can you all hear me now?

JOCELYN FERNANDEZ:
I can. Thank you.

DR. MATTHEW GOLDBERG:
Well, thank you. Thank you very much and thanks to Noridian for the opportunity to give comments here today if I can Dr. Vetto, tag me here with the response before I begin. But, just to highlight that, Dr. Clark's question here that, you know, unlike the gene expression profiling with decision DX melanoma, which provides prognostic information, I think about the BRAF and mutations you were you were speaking about, you know, fundamentally for treatment selection for targeted therapy. And not correlating necessarily, with outcomes. So just to kinda chime in at the discussion we were having previously before I begin.

I guess what I'd like to do now, is just introduce myself. My name is Matthew Goldberg. I'm a board-certified Dermatologist and Medical Pathologist and Medical Director at Castle Biosciences and I'm an employee and stockholder of Castle Biosciences.

In my comments today on the next slide here. I'll be reviewing the evidence that supports the existing LCDs. Highlight new publications have been published since the LCDs went into effect, and close with suggestions for changes to the draft LCDs that are currently open for comment. Now, the existing LCDs L37748 and L37750 are based on a strong body of evidence that have has only been strengthened since the last reconsideration, and therefore, the coverage criteria should remain unchanged.

Next slide.

The existing LCDs were approved by all 4 MACs based on 22 peer reviewed studies, which demonstrate the consistent ability for decision DX, melanoma gene expression profile, or GEP testing to improve the accuracy of defining risk for health outcomes of interest for patients who received the test result.

There's also a clear clinical utility to identify patients who can safely forgoes sentinel lymph node biopsy procedures and defined risk appropriate patient management plans independent from decisions to consider the sentinel lymph node biopsy procedure itself.

Next slide.

So, these next five slides were previously presented at an open meeting in October of 2019 and decision DX melanoma, as Dr. Vetto mentioned, was developed, and validated to assess the risk of recurrence and metastasis, independent from traditional clinical pathological risk factors for patients with Stage 1 through 3 melanoma and fundamentally, the test stratify patients with a class 1 and class 2 result. With the lowest risk in the class 2A group and the highest risk in the class 2B group.

Next slide.

Decision, DX melanoma helps physicians answer two questions that inform important clinical decisions and influence patient treatment plans. Specifically, what does the risk of a positive sentinel lymph node to inform sentinel lymph node biopsy recommendations? And secondly, what does a patient's risk of recurrence and metastasis after a melanoma diagnosis to inform decisions such as appropriate level of follow up imaging, multi-disciplinary referrals?

Next slide.

So AJCC Version eight staging provides risk stratification for patients diagnosed with melanoma and decision DX melanoma improves the prognostic accuracy of this risk stratification across Stage 1 through 3 melanoma. The table here demonstrates how HACC provides a population-based risk for each stage, which can be further stratified by combining the independent prognostic information from the GEP result. So, for example, AJCC V eight predicts that a patient with Stage two disease has a 90% five-year melanoma specific survival or MSS seen here in the black dot in the central column. Whoever has the arrows indicate that same patient would be predicted to have a five-year MSS greater than 99% with the class 1A GEP result. Which compares to almost 84% five-year MSS with a class 2B GEP resulting with a red arrow pointing down.

Next slide.

For Sentinel lymph node biopsy guidance, decision DX melanoma identifies patients who are low risk of sentinel lymph node biopsy positivity, who can safely avoid the procedure based on the currently accepted risk threshold of 5% predicted positivity that Dr. Vetto discussed. In the Medicare population decision, DX melanoma identifies a subset of patients with T1 to T2 melanomas meeting invasive melanomas that have Breslow thickness of two mm, or less, who fall below this, 5% predicted risk of sentinel lymph node biopsy positivity. And in here in this table from data and large cohorts patients with the class 1A result have a 1.6% rate of sentinel lymph node positivity and avoiding sentinel lymph node biopsy in these patients can reduce unnecessary surgical procedures while allowing improved resource allocation to those patients at elevated risk for positive sentinel lymph node.

Next slide, please.

So, in summary for this information presented previously and reinforced by Dr. Vetto’s presentation.

A decision DX melanoma influence a sentinel lymph node biopsy decisions and discussions for patients with invasive melanoma 2mm in thickness or less and further, the decision DX melanoma test influences decisions for follow up imaging and multi-disciplinary referrals for patients with melanoma zero-point 3mm and Breslow thickness of greater.

Move forward please slide two slides, please.

The next three slides focus substantially on how decision DX mode on the impacts the performance of sentinel lymph node biopsy decisions in the Medicare population with melanomas 2mm in thickness or less. And, again, one of the main findings from the 2019, Vetto et al. paper is that it predicts a patient the patients in this group who receive a class 1A when a result, actually have a less than 5% predicted risk of sentinel lymph node positivity and can safely forego the procedure.

So, the figures on the right side of this slide take this finding a step further and highlight that if the class 1A patients are managed according to these findings, 65% of patients in this cohort could safely forgo the sentinel lymph node procedure and this ability to reduce unnecessary sentinel lymph node biopsy procedure is also holds for the T1 and T2 melanoma subsets independently, when viewed separately, seen here at the bottom right of the slide.

It's important to risk stratify patients, with these thin invasive melanomas, is because Medicare eligible patients with T1 and T2 tumors currently undergo this sentinel lymph node biopsy procedure. And what guidelines may not endorse, the sentinel lymph node biopsy procedure in patients with T1A melanomas, remains important to triage these patients, are significant numbers of Medicare eligible patients with T1A melanoma, currently undergo a sentinel lymph node biopsy. And what's more approximately, 42% of patients with a T1A melanoma undergoing the procedure don't have high risk features.

Next slide, please.

So, for illustration, we've modeled here what this would look like in current practice.

Next slide, please. Thank you.

In current practice based on data from surgical oncology centers. So, in patients with T1A melanoma 65 years and older that have the sentinel lymph node biopsy procedure performed, 94% will have a negative result and received no benefit from the procedure.

Next slide, please.

But in these patients who underwent a sentinel lymph node biopsy surgical procedure as part of their clinical care, Decision DX melanoma identifies 82% of patients with a class 1A result who can safely forego the sentinel lymph node biopsy procedure and GEP testing in this group would reduce a large proportion of unnecessary procedures while improving the yield of sentinel lymph node positive results. In surgical procedures still performed for the non-class when 1A GEP results.

Next slide, please.

We switch gears, independent from the sentinel lymph node biopsy decisions. Clinicians treating patients with melanoma are also looking to address the question of: what does the risk of recurrence and metastasis, and published evidenced by Marks, et al. established a floor for GEP testing at zero point 3mm Breslow thickness or greater and the data support the zero point 3mm cut point for risk stratification of patients who may be at elevated biological risk of recurrence and distal metastasis whose clinicians will change management following GEP results and importantly, both clinical utility studies analyzed in the Marks paper, reported the proportion of management decisions prior to the publication of the 2019 Vetto, et al. manuscript, that describes the use the test to inform sentinel lymph node biopsies as discussed in the prior slides. So, therefore, taken together the clinical utility Decision DX Melanoma described in Marks, et al. combined with the ability to avoid unnecessary sentinel lymph node biopsy procedure described in Vetto, et.al 2019 highlight the significant clinical actionability of the test for patients with T1 and T2, melanomas.

Next slide, please.

Since the reconsideration request in 2019, the evidence supporting the utility of Decision DX melanoma has increased, and reconsideration of evidence included in the draft LCDs should include the whole body of recent evidence.

Next slide, please.

The inclusion of supportive articles in a revision to the LCDs would be important, because it would provide an improved context of evidence available for the Decision DX test. Specifically, these additional articles, blow address points raised in the recently modified text of the draft LCDs. For example, all Stage 1 and 2 patients included in the Greenhaw meta-analysis have been staged using AJCC V8 and the paper includes multi variable analysis that demonstrates that statistical independence at the decision to excellent number test from the clinical pathologic factors incorporated in staging and the same can be said for the Arnot study and Dr. Hsueh, et al. study as well. For the next several slides, we'll walk through highlights from the Greenhaw, and Hsueh studies.

Next slide, please.

Decision DX melanoma is consistently a significant predictor of risk, independent, of all relevant prognostic clinical and pathologic features across multiple studies, and it's important to highlight that outside of a AJCC V8 staging, there is no other nationally accepted tool available that integrates all clinical and pathological features to provide prognostic information. And, therefore, evaluation of the ability of Decision DX melanoma to improve the accuracy of defining risk for tested patients has focused on comparisons to multiple clinical pathologic factors in AJCC V8 stage.

Next slide, please.

The table here on this slide is adapted from the Greenhaw, et al. meta-analysis and demonstrates that in the cohort of 1479 patients Decision, DX melanoma significantly stratified risk within AJCC stages, this study highlights how Decision DX melanoma can serve as an adjunct to staging, not a replacement for staging. Survival rates from the AJCC only demonstrates stratification of melanoma specific survival and don't get information on Recurrence Free Survival (RFS) and Distant Metastases Free Survival (DMFS).

This information is used by clinicians to guide important management decisions such as frequency of follow up, imaging and referral to multi-disciplinary clinics.

Next slide please.

A decision DX melanoma, significantly stratified risk within a AJCC stages, it provides added prognostic information to an approach that relies on AJCC staging alone. Based on a recent prospective study from Dr. Hsueh, et al., patients with early-stage disease and high-risk class 2B results have a recurrence risk similar to patients with later stage disease, were currently recommended to receive more intensive follow-up surveillance imaging and referral to multi-disciplinary care. So, in this way, Decision DX melanoma testing identifies a level of risk in early-stage patients. That is determined to be clinically actionable by national guidelines.

Next slide, please.

Further, Dr. Hsueh, et al. studies show that overall sensitivity of risk prediction is enhanced when decision DX melanoma in AJCC V8 staging are combined, as Decision DX melanoma is more sensitive than AJCC alone, for prediction of RFS, DMFS, and death.

When combined decision DX melanoma and a AJCC staging accurately identify 76% of occurrences and 88% of metastases in the study, compared to 57% of occurrences in 62% of metastases if AJCC staging is used alone.

Again, this recently published prospective multi-center study, should be considered by the draft LCD as it demonstrates that decision DX melanoma improves the accuracy of defining risk for health outcomes of interests for metastic patients.

Next slide, please.

This from the study of Greenhaw, et al. all again.

In a cohort of 867 patients who received both GEP testing, and the sentinel lymph node biopsy procedure, showed the Decision DX melanoma outperforms the prognostic accuracy of sentinel lymph node biopsy for the endpoints of occurrence and distant metastases. But what is more in the bottom rows at the table, if you define high risk as either a positive sentinel lymph node biopsy or a class 2B GEP result, the accuracy metrics for risk prediction improved further and achieve the sensitivity of 88% for RFS and 90% for DMFS. This again highlights the decision DX melanoma augments current risk stratification approaches when GEP results are considered in the context of AJCC staging.

Next slide, please.

So, since 2018, the original LCD effective date Decision DX Melanoma has been ordered on Medicare patients by 4700 clinicians, at over 2700 institutions, including 40 leading academic centers. Decision DX melanoma has been included in the multi-disciplinary workflows that many academic hospitals to integrate AJCC staging in Decision DX testing across the spectrum of patients with Stage 1 through 3 melanoma and schematics of those clinical workflows are seen here in the images the bottom of the slide.

Next slide, please.

So, in conclusion, the data published to date continue to support the validity and utility of decision DX melanoma to identify patients with tumors 2mm in thickness or less, have a low risk of metastasis to the sentinel lymph node, and can safely forego the sentinel node biopsy surgical procedure in the Medicare population.

We request for consideration of research that evaluates Decision DX melanoma test results in conjunction of AJCC Staging and other clinical pathologic features to improve accuracy of risk prediction for patients for Stage 1 through 3 melanomas. The recent Grossman and Marcetti articles recently added to the draft LCDs do not contribute additional tested patients to the published literature and have limitations that are not currently outlined in the text of the draft LCDs. The Grossman article is an opinion statement informed by survey data with a low response rate of only 14% to both surveys, and Marcetti, et al. does not make comparisons of the accuracy of GEP testing to the accuracy at AJCC staging alone or consider the improvement in prognostic accuracy provided by combining gene expression profiling with AJCC staging approaches. As has been performed in studies such as Greenhaw, Hsueh, Arnot and others and what is more, both articles do not address the clinical utility of the Decision DX melanoma test to inform sentinel lymph node biopsy decision making.

Finally, around 8000 clinicians and thousands of institutions have adopted the Decision DX melanoma test to improve patient care. and there are many physicians with clinical experience for how GEP test results can be incorporated into their clinical workflows to inform management decisions for their patients.

Next slide, please.

And lastly, what we will submit specific language for the draft LCD modification during the open comment period. Broadly speaking, we recommend removing the two paragraphs recently added to the draft LCDs that site the Grossman and Marchetti articles. But in the event that the two proposed paragraphs remain in the LCD we recommend, including a discussion of limitations of both articles, as well as a thorough discussion of the numerous studies published since the LCD went into effect that further support the prognostic accuracy of Decision DX melanoma to guide sentinel lymph node biopsy decision making, and augment risk prediction for recurrence and metastasis, many of which were discussed in this brief presentation.

So, I just want to thank you for your time and attention.

DR. LARRY CLARK:
Thank you.

Is it your expectation that we have archived speaking, speaking as MolDx as multiple contractors, we have those additional articles archived, or would it be prudent for us to get them from you?

DR. MATTHEW GOLDBERG:
We would be more than happy to provide those relevant articles to you in PDF form or in, you know, with DOI links. If that makes sense. We'd be responsive to whoever, However, you'd like us to inform you of that set of other published literature, kind of some of which are listed in that in that table, we can get that to you in an actionable form, if that makes sense.

DR. LARRY CLARK:
Dr. Graves?

DR. ANITRA GRAVES:
I have no questions that, yes, the PDF format would be excellent, if we could get that evidence of that would be great. Thank You.

DR. MATTHEW GOLDBERG:
We can plan on that. We can plan on that submission with PDFs to Noridian directly.

Which e-mail, just to clarify, where would you like this sent just to follow up? Sorry about that.

DR. LARRY CLARK:
Jocelyn, we have our draft policy e-mail boxes that works the best.

JOCELYN FERNANDEZ:
The e-mail you can send it to, is policydraft@noridian.com

DR. LARRY CLARK:
Thank you.

DR. MATTHEW GOLDBERG:
Thank you very much.

JOCELYN FERNANDEZ:
Thank you, Dr. Goldberg,

DR. LARRY CLARK:
Yes. Can we move on to our next speaker?

JOCELYN FERNANDEZ:
Sure. Thank you, Dr. Goldberg, for your comments.

The last commenter, for this proposed LCD is Dr. Darrell Rigel. Dr. Rigel, your line is open.

DR. DARRELL RIGEL:
Well, thank you very much.

Thank you Noridian and thank you, Dr. Graves and Dr. Clark, for allowing me to present today.

By way of conflict, I do consult with the company, but I'm not being compensated for my presence today.

And I will say that I am a clinician who uses this test regularly from my patients, with my Medicare patients, certainly, and I see the value of this test and that's really why I'm here today to try to focus on that. Just by way of my background. I'm leader of many of the groups within academic dermatology.

So I've been involved with that but perhaps more importantly for this presentation I am a melanoma researcher. I’ve given over done over 250 papers given over one thousand lectures in the field and as an aside, I'm actually the co-developer of the ABCs of melanoma was 40 years ago, it doesn’t seem like that long ago but it was, and it's certainly something that's called on for early detection. We're going to focus today, though, a prognosis of assessment of sentinel node positivity.

Next slide, please.

So, we're going to talk about several things today, but I think the two most important take home message today by giving you those are that number one, is, this test, really is very useful. The data strongly supports the value of this test. I think I want to emphasize that I'm trying to not be redundant with it with the two prior presenters.

But I think the importance of maintaining this policy, it's really very important because it really is for our Medicare patients. They really have the ability to use this as a tool for our patients to better assess prognosis and also really lower the number of unnecessary, sentinel node biopsies to perform, especially in the T1 patients and we'll go over that as we go through the data.

Next slide, please.

So, you know, I think the important part is at several points here, the existing LCD is appropriate and supported by strong evidence, as Dr. Goldberg just refer to you and Dr. Vetto, mentioned some of these too. There are a number of studies that have come out since the last the LCD that really support this. And, I think, if you do a review and this comes forward, all these papers need to be included and I know that Dr. Goldberg said he’ll get them for you, which is great, but they're all extremely important for coverage with this.

And I think the other part of this is that you do, in this proposed LCD, they mention to the two articles, the Marchetti article and the Grossman article.

And I know both of the very nice people, but I think in this case, they really have not done an appropriate analysis for this, and we'll talk about that in a moment.

But the fact is, that Marchetti is, really, it's just study it, just analysis from other results that really has its flaws and Grossman was really not reflect the widespread consensus of using this, and I'll explain why in a moment. But there has to be a fair balance of this, and, I think, given the data that's out there, and that data studies you've heard you look at, and we'll talk about a little bit. There are 20 plus peer reviewed articles using different data sets from different institutions that consistently demonstrate the validity and efficacy of the test.

Next slide, please.

So, let's talk about the Grossman article and, again, Dr. Goldberg alluded to this, but this was a survey with a very low response rate, and I think the problem with it, it was a majority opinion. This was done using the Delphi process was 50% required in order to achieve consensus.

I think you probably are both Delphi procedures. That typically is reports are 80% interminably, two thirds.

And there was a strong minority view that were not included in those papers because we purpose to get to this.

In addition, the people who were surveyed for this were primarily from academic with larger referral practices, and a number of them came from a single institution. They really weren't representative of the national view. And I'm going to contrast that to another study in a moment. There was also potentially participation from ex-U.S, individuals' data for that, the test is even offered there and there were also people in the study. And the survey who are not physicians, they were data scientists. They don't treat melanoma patients and 13 of the contributors of a group who actually responded were all from the same institution, the University of Utah.

So, I think all these calls it the question, to some extent said, about the, I'll put it quote, “consensus that was achieved”.

Next slide, please.

Now, in comparison, I wanted to show you another study that was also published last year. This is actually earlier this year. This is the Morrison study and what this looked at it was kind of actually gives us 589, almost 600 US based Dermatologists that demonstrated the value of the GEP test and guiding patient management decisions.

And what they showed is that the clinicians indicated benefits of using the 31 GEP test and again, I will be generic in my terminology for this. Identifying true negatives, in the low-risk population, the value of identifying true positives in a low-risk population.

They are identifying true negative patients at high-risk populations, and what they also showed, as I'll show you in a moment with some of the follow up on this test, it actually changed management in the appropriate direction, in the majority of cases when this data was added to the other prognostic factors that were known with the patient.

And I agree with Dr. Vetto. It's very clear this test is not meant to be alternative. To the other fact, is rather having this data is synergistic with the other factors like age AJCC, in terms of better assessing prognosis and also, candidates for sentinel node biopsy.

Next slide, please.

Now, to put it into context, this was another expert panel of 5 dermatologists that was published late last year looking at the same data. And I think the importance of here this this consensus was they had to achieve a higher percentage for it to be a Delphi accepted consensus.

And the point is that they came up with the fact that this should be included in multiple disciplinary discussions to determine appropriate patient management decisions. And the workflow should be under the umbrella of national guidelines and it fits and that a patient's individual risk of recurrence to drive the management decisions. I think that's what we all want as clinicians to do that.

Next slide, please.

So, one of the things that was particularly important and mentioned in the proposed LCD that is inaccurate, I really want to bring this to your attention, because this is alluded to in the articles that we just talked about. But it's absolutely inaccurate and not true and I want to emphasize that.

Is that when you look at AJCC staging, excuse me, you have the major factors that are in there. And then, of course, mitotic rate was taken out in the eighth edition.

But when you look at this data, and you add to it, the data from the 31 GEP test. The value, it, synergistic, it’s not overlapping. It's not impacted negatively with this, and it says that the performance may be compromised when assessed in the context of full list of factors, that is not true.

Again, look at these data, these are independent factors, multiple studies showing that the 31 GEP, as is the independent prognostic factors statistically independent for that.

Next slide, please.

Next slide, please.

OK, there we go, and this is looking at a bunch of the studies. Please go back one, I'm sorry. Go back. There we go.

This is also confirmed by a number of studies, many of these were alluded to, I won't beat on a dead horse with this But, but I do want you to focus on, is the end of these studies, and these are actual studies that we looked at.

The top two were actually meta-analysis that were published in major dermatology journals all recently in the last year. Showing the same thing. That in fact, there was utility to this test, independent, statistically significant additional information that was supplied in terms of prognosis as well as sentinel node biopsy.

Next slide, please.

OK, now, as we went through this, this is, this is, I think, some really important points here in the Marchetti again, it's a sort of an opinion is that really a study. But we'll call the paper. It inherently recommends that all patients should get a sentinel node biopsy or within melanomas and that's just not true.

And the nice thing about this test, it identifies patients, as Dr. Goldberg alluded to, with our T1 patients that do not require a sentinel node biopsy. So instead of just guessing who needs it, if it doesn't need it, you have an objective way of determining this. every with patients may not be this.

And the other they think that it's very important that's lacking in the analysis of this paper is they did not use traditional endpoints, relapse free survival, distant metastases, re survival, and melanoma specific survival. When you use those endpoints, the data becomes strongly statistically significant.

Let's look at the next slide just to demonstrate that.

So again, these are from the Litchman study that was done in the meta-analysis done in skin.

And what you see from that, again, if you look at the risk for sentinel lymph node positivity, look at the odds ratios there. You can see the significance of all of them except for the Keller paper. It was the trend, but not significant.

Look at the risk of metastasis or death through the melanoma again, all highly statistically you see live with odds ratios significantly greater than one.

So, again when you can you use the standard endpoints, they use typically for melanoma survival, relapse free this in the past is free and overall survival and central load positivity, there are all statistically really significant in these larger datasets where the analysis is done, and that's kind of ignored by the Marchetti paper.

Next slide, please.

Now, the other thing that's really important, and I think this is very important, this is from the Greenhaw paper, but if you look at this stagging in AJCC, and that's the column, I guess my pointer doesn’t work here. But the column that's over on the left, and you see you have the relapse free survival of with DMFS of 5 year.

What you see when you add the data from the 31 GEP test with the four classes, a statistically significant differentiation and goes, monotonically, decreasing survival from class 1A to class 2B, and look at the difference of the overall survival. Let's say of a Stage 1, the RFS survival. Almost 98% and DMFS almost 98% and at a class 1A, compare that to a class 2B. If you have a patient that's, you know, 76 to 80 or so percent survival, you're going to manage that more aggressively. That gives you that information. But alternatively, the other side of it, 98% of survival. You don't need additional patents that you follow that just clinically with observation and look, you see similar data for the Stage II and Stage III patients for that. So, to me, that's also very compelling that the data from this test is additive, in fact, synergistic with the staging from AJCC.

Next slide, please.

Now, again, these are six additional studies, if you think about, why do you do a test, you do a test, because you want to alter your treatment decision point. You want to go one way the other. Well, these six studies basically show the clinical utility and impact of the 31 GEP testing.

The first three stages are clinical utility studies. And what you see from this is with the data, these are all independent data sets, and with the data, you see the management changes. almost 50% of the management changes, and in the appropriate direction, for adjusting based on the change and assessment, in terms of prognosis and then the bottom three studies, there are clinical impact studies, Again, all done with different data sets, looking at this by showing that there was an overwhelming majority of the risk appropriate management change. So, the impact was very strong.

Next slide, please.

So just conclusions with this. I think it's very important to remember that these new, the two articles, that you included should be interpreted with caution.

Next, please.

There's significant methodological flaws and analysis of the two articles that I reviewed with you. I think of material. They limited their evaluation to a population following full staging, where they considering use for sentinel node biopsy, in another words, where they basically said everybody in that group had a sentinel node biopsy. That's not what really is done in the clinical setting.

Next slide, please.

There was significant additional evidence that's come out supporting he LCD that has been published since the last rest review and if you're going to have this, this should be included in any revision.

Patients with Stage 1 melanoma, the fact that some well metastasize to die from the disease. And these high-risk subsets of these low-risk patients are not really well identified by today’s tagging practice. But they are identified using that 31 GEP tests, I think that's important.

Next, please.

I think, I hope I've shown you, and giving you the information. That is extensive evidence that supports the clinically actionable risk stratification, additional prognostic value of the 31 GEP test when combining it synergistically with the AJCC staging, especially the Stage I patients where there is significant overuse, in my view, of sentinel lymph node biopsy.

So, again, this test is very important. I use it on a regular basis. It helps my patients. It helps me manage them and I hope you'll consider that as you go forward with the proposed LCD. Thank you very much.

DR. LARRY CLARK:
Thank you.

JOCELYN FERNANDEZ:
Thank you, Dr. Rigel for your comments.

Moving on to the last proposed LCD, MolDX Multiplex Nucleic Acid Amplification Test Panels for Infectious Disease Testing.

There is one presenter, Ms. Molly Broache.

MOLLY BROACHE:
Good afternoon can you hear me?

JOCLEYN FERNANDEZ:
Yes, I can.

MOLLY BROACHE:
Wonderful, thank you so much.

Excellent. Well, I really appreciate everybody's time today to talk about our molecular tests for BD Max Vaginal Panel. And to introduce myself, I'm Molly Broache. I am a Senior Global Medical Science Liaisons with Becton Dickinson Integrated Diagnostic Solutions. I'm also a women's health nurse practitioner.

Today, I am here to request that CPT code 81514 be added to the Noridian draft LCA Number DA58270.

I also want to comment on the positive verbiage in the draft LCD regarding the BD max vaginal panel. And again, I thank everybody for their time today.

Next slide, please.

So, our agenda for today. I'll be discussing the verbiage in your draft LCD regarding BD Max Vaginal Panel as well as a new study that was published in 2020 by one of our collaborators. The new study was not referenced in the draft LCD. Most likely because it's very new literature.

Next slide please.

As stated within the draft LCD we agree that the BD max vaginal panel performance has shown very high sensitivities and specificities as shown in this table in orange.

These panels have shown to perform better than clinician assessment or traditional methods, which are not often performed, which are often in the case of vaginitis, gram, stains, and microscopy.

And, further, high rates of co-infection with STIs, about one quarter of patients who have vaginitis, actually have been shown to have STIs as well.

Panels detecting sexually transmitted pathogens have become routine in clinical laboratories as they provide a rapid result for organisms like chlamydia species that can be difficult to culture.

Moreover, it is well established that Neisseria gonorrhoeae, and chlamydia is not only causing similar clinical syndromes, but also coexist in a significant proportion of patients, highlighting the need for panel testing.

So, again, this just really shows sort of the public health implications that often, with women are not screened for vaginitis within that, they are often not screened for STDs as well.

Next slide, please.

Here I'll provide a summary of the benefits of the BD Max Vaginal panel, and I want to re-iterate to the group the summary.

So, vaginitis results in millions of physicians visits each year, unfortunately, 40% of women will leave their initial physician visit without a proper diagnosis.

The BD Max vaginal panel provides clear results and supports diagnostic accuracy of vaginitis.

When I say clear results, what I mean is there are no indeterminate or intermediary results that come back on the vaginal panel. It is a qualitative yes/no diagnosis for the three major causes of vaginitis or vaginal discharge syndromes being bacterial vaginosis, vulvovaginitis pandomyosis, trichomonas vaginalis.

Additionally, the BD Max Vaginal panel is designed to provide actionable, positive, and negative results through the utilization of a unique BD algorithm.

So, with this panel, we are not just looking for one bacterium as an indicator. For BD, we are actually looking at multiple organisms that have been proven in the literature to be a component of bacterial vaginosis.

We also have an ability to identify resistant Candida species with this panel. So, in the case of this panel, we report out candida glabrata brought out in candida krusei separately. These species of yeast are very important to identify because they often don't respond to a single dose of fluconazole and often these candida infections can be seen in women in the Medicare age population.

The next BD Max Vaginal panel supports the improved diagnosis of vaginitis which enables accurate prescribing, and, therefore, has the potential to reduce the need for repeat physician visits and re treatment.

One of the issues I've seen in clinical practice is that when you aren't using a highly sensitive test, the first time that patient presents and some of these empirically diagnosed, or, or, I'm sorry, empirically treated, or sort of just treated based on symptoms, they often come back to the office within 1 to 2 months still needing treatment because maybe they were treated for the wrong cause of vaginitis.

Or maybe they were overtreated and didn't really have an infection.

And the prescription itself for treatment itself resulted in our negative sequelae.

Additionally, improved vaginosis diagnosis may also help to reduce the risks of costly negative sequelae, including those related to pregnancy and STDs.

So, imagine vaginitis in itself is not really considered an STD. The increased risk of STDs along with a positive vaginitis diagnosis has been well proven in the literature.

Next slide, please.

Right here, I want to briefly go over the study design and the key conclusions from additional literature supporting the draft LCD.

The study from Hillier et al, titled, Diagnosis, and Treatment of vaginal Discharge Syndromes in Community Practice Settings further substantiates the positive verbiage in the LCD for not testing in the urogenital and anogenital category.

So, to go over the study design this was a multi-center single visit study that compared clinician diagnosis of vaginitis to CDC recommended laboratory-based testing and the BD Max Vaginal Panel.

Within this study, there were 303 women, ages 18 to 45.

They were enrolled between July 2017 and March 2018, resulting in 290 valuable specimens.

The study included eight community-based practice clinics affiliated with the University of Pittsburgh Medical Center.

So, women did have to have symptoms of vaginitis to be a part of this study. And BD Max Panel and all intended use is for symptomatic wherein it is not a screening test.

The key conclusions from this study were that CDC recommended point of care testing such as vaginal PH, microscopic examination of vaginal fluid and the whiff test is infrequently performed for evaluation of women from the setting with symptoms.

Imagine us, unfortunately 4 out of 10 women seeking treatment for vaginitis are prescribed inappropriate treatment based on the fact that in this study, the MAX vaginal panel results came back later. So, women were treated based on that office’s assessment that often-included point of care testing.

Women prescribed unneeded treatment were significantly more likely to return with symptoms of vaginitis and those who were not treated.

So, I think this does show that some of these women might not even have one of these major causes of vaginitis. So, we are often given antibiotics antifungal to women who do not even need them and that may cause more harm and make them return to the office.

So, leading to the fact that empiric treatment, which is common and perceived as causing no harm by many, may result in a greater burden on the medical system to speak from my own experience. I have had patients actually just, you know, call in and ask our nurse and medical assistant staff for a prescription, because somebody, you know, knows they have bacterial vaginosis. And they might very well be right, but they also might very well be wrong, and, like, offering somebody, the ability to have a test, like a nucleic acid amplification test that has quick return, and actually providing that correct prescription for the correct condition of vaginitis is just really critical and trying just stop the cycle.

Next slide, please.

CPT code 81514 just went into effect on January 1st of 2021, the CPT code description for 81514, or is included on this slide for your reference, I will just read it.

It's Infectious disease bacterial vaginosis, an vaginitis, quantitative real-time amplification of DNA markers for Gardnerella vaginalis, Atopobium vaginae, Megasphaera type 1, Bacterial Vaginosis Associated Bacteria-2 (BVAB-2), an Lactobacillus speciest (L. crispatus and L. jensenii), utilizing, vaginal-fluid specimens, algorithm reported as a positive or negative for high likelihood of bacterial vaginosis, includes separate detection of Trichomonas vaginalis and/or Candida species (C.albicans, C. tropicalis, C. parapsilosis, C. dubliniesis), Candida glabrata, Candida krusei, when reported

That is a very long description. But just FYI this actually results in five result reports for the ordering physician. Would be one result for BV utilizing that algorithm. One result for trichomonas vaginalis and then 3 results: 1 for a candid group that includes those four species of Candida: one for glabrata and one for krusei.

We notice that this most applicable code was not listed on the draft LCA.

We ask that you add CPT code, 81514 to the coding article as the codes, 87481, 87661, 87801 which are included, are no longer the most appropriate codes to bill for the BD MAX vaginal panel.

So essentially, we have a singular code now before there was billing of essentially five different codes for those five different causes of vaginitis.

Next slide, please.

And these are our references, and we're happy to share any PDFs. Most of these articles, I will say our open access as well and I really appreciate everybody's time and attention regarding CPT code 81514.

Thank you very much.

JOCELYN FERNANDEZ:
Thank you, Ms. Broache, for your comments.

This concludes the presentation portion for today.

We will now move on to closing and next steps.

In closing, we would like to communicate the next steps in the policy development process.

The comment period for the proposed LCD started on May 20th, 2021 and will remain open until July 3rd, 2021.

As noted earlier, all comments to be considered by our medical directors for their proposed LCD's must be submitted in writing.

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

Information for our proposed LCDs are located on our website at noridianmedicare.com. Upon review of the comments our medical directors will either finalized or retire their proposed LCDs.

Please monitor our website or register for list serv notifications to be informed of actions taken on our proposed LCDs. I will now ask Dr. Clark or Dr. Graves for any final comments.

DR. LARRY CLARK:
Well, I just want to thank our, all of our speakers for thought provoking presentations.

This is, I certainly think today is, is what this process is supposed to be, and I appreciate the serious intent of all of your presentations.

And I'm going to ask Dr. Graves if she has any additional thoughts or comments, and also Jocelyn, do we have any other meetings that we might want to let our attendees know about? I just encourage you to keep following our website, Dr. graves.

DR. ANITRA GRAVES:
I have no other comments to add. I too very much show my appreciation for the effort that presenters made to provide us information that will be helpful in the policy development.

With respect to those that are proposed, we appreciate that the evidence evolution is more rapid as we go along, and we are mindful of that. So, appreciate bringing to our attention new evidence that are, that should be, take it into consideration when finalizing these policies. So, thank you again for participating in this open meeting.

DR. LARRY CLARK:
We’re taking off into a non-Halstedian world, so thank you, Jocelyn.

JOCELYN FERNANDEZ:
This concludes our meeting. Thank you, everyone, for attending, and enjoy the rest of your day.