Each spring CMS publishes proposed Part A inpatient rules, and finalizes them around August 1. Find the information here:
In a press release on August 2, 2022, Guardant announces it has received Medicare coverage for its REVEAL test, which is a direct measurement of residual disease in plasma of stage 2 and 3 colorectal cancer patients.
See the press release here. See early coverage at Genomeweb here.
The coverage comes under a "foundational" or "umbrella" LCD that allows MolDx to cover liquid biopsy tests for
Under that umbrella, MolDx makes test by test and context by context decisions. For example, Test A might be approved for detection of relapse in colorectal cancer, and test B might be approved for detection of response to therapy in liver cancer. See LCD L38816.
Two weeks earlier, Natera announced coverage by MolDx for MRD testing in bladder cancer, notably, on cited 2019 and June 2021 publications. (Powles, Nature, 2021; Christensen, J Clin Oncol, 2019). This suggests the case-by-case MolDx review process is not real fast.
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On ctDNA in bladder cancer, see also a short review by Fenner . Friends of Cancer Research published a white paper last winter on ctDNA as a regulatory endpoint in cancer drug trials, here. On the other hand, the June 2022 ESMO guidelines Pascual et al. on ctDNA focus on CDx applications for drug selction, not yet ready for a full recommendation for MRD applications for treatment path management.
Natera's test is a per-patient bespoke test based on exome analysis of the tumor. Guardant's test is a pre-designed test which is the same for all patients. Multiple companies are looking at either approach to MRD. Positive reports appear regularly (breast cancer here, colon cancer here,) while negative reports (here) appear from time to time also.
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A few weeks ago (June 9), I issued a blog about a novel new LCD for cancer biomarkers at Novitas - here. The LCD primarily acts to refer coverage of cancer biomarkers to outside guidelines and databases. About the same time (June 12), I issued a blog about "Medicare test coverage without any articles." (For example, someone would ask me, "Company A says its test is covered, and it bills under Novitas, but I can't find any statement anywhere.") Here. Of course, searches are always imperfect, and the only answer with a null search is that, "the rules were hard to find."
Usually, when I get these requests and can't find a MAC published article, I submit a FOIA request to the MAC for any internal documents or correspondence about covering and pricing the test of interest.
Press Release about LCD
Here we have a press release (August 1, 2022) from Pacific Edge Bio, about how the new Novitas LCD would impact its coverage. Bottom line: They say the impact might be negative. Here.
Here are some procedural comments, by Pacific Edge, about its current experience with the US LCD revision process at Novitas:
...Having consulted with our US-based advisers and industry experts, Pacific Edge believes the proposed changes are unlikely to survive the ongoing review process in their current form. The consensus view we received was that the proposed changes to the LCD are contrary to US legal requirements and precedent....
What does Pacific Edge think of the LCD and LCA?
Pacific Edge believes the proposed LCD and LCA will not survive in their current form because:
What is Pacific Edge doing to change the Novitas proposal?
Pacific Edge has presented in person to Novitas and has made a detailed submission comprehensively setting out its concerns and the drawbacks of this new approach. It is also sharing insight with other biotech companies that could be similarly affected by the new approach to make their concerns known to Novitas before the end of the consultation period, and engaging with industry advocates.
If the draft LCD was first published in June, why did Pacific Edge only notify the NZX and ASX and call a trading halt on Friday 29 July 2022?
In June the draft proposals did not appear to affect Pacific Edge since there was no indication that coverage for Cxbladder under its existing LCD was changing. Additionally, Cxbladder was not explicitly mentioned in the proposed LCD.....(continues)
Posted: 7/28/2022 NOVITAS
Note Posted on MCD 07/28/2022:
As communicated on our website on 07/25/2022, the Comment Period End Date has been extended for this Proposed LCD to 09/06/2022. The original Comment Period End Date was 07/23/2022, which displayed on the CMS MCD from 6/9/2022 through 07/28/2022. The extension is due to changes being made to the related draft article.
Please refer to the Related Local Coverage Documents section at the bottom of this Proposed LCD for changes made to the draft article (DA59125, Billing and Coding: Genetic Testing for Oncology) The changes are indicated on the document note at the top of the document.
Precedents
I've been meaning to write a blog (or vlog) about precedents for using guidelines for LCDs.
For example, the NGS MAC article A56199 for BRCA testing simply points, in a short statement, to the current NCCN guideline. The MOLDX and NOVITAS MACs have LCDs for pharmacogenetics primarily simply point to the FDA guidance on PGx genes and the CPIC guidance and reviews on PGx genes (L38337). Then, there is this new proposal for Novitas which ties cancer biomarker coverage to NCCN (and a couple other) guidelines. MOLDX recently finalized a hereditary cancer testing LCD L38966 which has a heavy emphasis on a reference to outside guidelines, as well.
Other times, efforts to tie LCD coverage to guidelines has flopped and quickly. In May 2016, Noridian posted an LCD that simply tied breast cancer gene expression tests (eg Oncotype, Mammaprint) to "current ASCO guidelines." This LCD was proposed and withdrawn in a time cycle of just a few weeks. Here.
CMS guides Contractors to weight guidelines in their LCDs, along with RCT evidence. CMS has made national decisions that block coverage of future products that CMS has never reviewed, as discussed recently by Selkoe here.
This month, two significant CMS positions on software and algorithms appear in proposed rules, which are open for comment for 60 days.
One focuses on software in the Hospital Outpatient (APC) setting. The other focuses on use of parameters like age, sex, race in "computer algorithms" and decision support, to avoid "discrimination."
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The non discrimination (and computer algorithm rulemaking) is here and will be officially published in the Federal Register on August 4; comment to October 3.
SEE THE FINAL PAGINATED VERSION, FED REG, AUG 4, 2022. 87 FR 47824-920, comments to October 3. Here.
Press release here July 25. See comment at Health Affairs here and Foley Hoag here. The rule, and the comments, also touch on the back-and-forth history of some of this regulation which stems from ACA 1557. I provided a little back story in my July 26 blog here. It does things like amplify Section 1557 by stating that sex discrimination is defined to include gender identity factors, so that sex discrimination extends to conditions like gender surgery.
The hospital outpatient annual rule is here (87 FR 44502, 7/26/22) and comment open to September 13. Focus in this blog on software policy.
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AGE, SEX, ALGORITHMS AND AI
Regarding non-discrimination and algorithms, CMS proposes that under Section 1557 of the Affordable Care Act, algorithms that use gender, sex, age, or other conditions in a discriminatory way are not allowed.
It's not entirely clear to me (either from the text of the rule or the early commentaries cited above) how this impacts AI or other clinical algorithms that depend on sex and age as major drivers of their accuracy.
Discussion focuses on situations where there have been discriminatory algorithms such as race-weighted algorithms for kidney disease. However, it is common Bayesian statistics to weight predictions by baseline case states, such as the rise in cancer with age.
The discussion is at page 176ff of the draft rule PDF, and the regulation itself is very concise at 92.210 (page 305). "A covered entity must not discriminate on the basis of race, color, national origin, sex, age, or disability in its health programs and activities through the use of clinical algorithms in its decision-making."
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HOSPITAL OUTPATIENT PAYMENT: MORE ON SOFTWARE
We were talking about the nondiscrimination and equity rule (algorithm section). Shifting gears.
The regular annual hospital outpatient proposed rule is published and paginated in the Federal Register 7/26/2022, 87 FR 44502 forward. Here. Pricing specific to the Heartflow product is again discussed, page 44569ff. However, in this blog, I would point to the later, and lengthy, general discussion of hospital outpatient software pricing, at 44684ff. This section is titled, "OPPS Payment for Software as a Service."
Note there are some potential differences between physician office (PFS RVU) pricing and hospital outpatient (APC) pricing. Office services are paid by piecemeal CPT codes, although CMS has an option to bundle software costs as overhead vs more specific recognition of costs. CPT codes may contain specified components,e.g. "injection procedure, includes ultrasound if performed.")
Hospital services are paid in broader payment categories (e.g. Radiology Level 1, Radiology Level 2, etc) where different services and often their components are bundled in on APC. To give a simple example, a PET scan and its radiotracer are paid separately in the physician office setting, but the tracer is secondary to (not paid separately) the PET scan in the hospital outpatient setting.
Turning to software as a service, CMS discussion extends from page 44684 to '89, in pretty fine print, and I'm not sure I've absorbed it fully. They are describing what they see as problems for software payment, and in particular focus on imaging software that occurs later than the original CT scan or other imaging, and involves an interpretation technology different than that paid for by the original clinical interpretation. (E.g. very sophisticated next-level software ordered for heart vessel blood flow aka Heartflow company). CMS is focused on seeking comment on its alternatives for this very important topic.
They are dubious of licensing and per click software, "empirical research has shown that pay per use may lead to overuse of AI technology." I suspect somewhere down the line, they don't want a $1M MRI machine with software converted overnight to a $1M MRI machine plus a $1M software package to allow it to be turned on and used.
In July 2022, AMA announced codes for software used in pathology for whole slide imaging, as Category III codes that could be "added" to existing surgical pathology codes. It's unclear whether, in December, CMS will view this as payable in the APC setting or bundled to the primary surgical pathology code. (And in fact, I understand that primary surgical pathology codes for hospital outpatients are now already usually bundled to APC fees to the hospital for the surgery). Much to be written on these topics in the coming months.
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Though not related to software, some readers may enjoy discussion of payment for Category B investigational trial devices, page 44683ff of the outpatient rule. The outpatient rule on software also has a quick call-out to AI and racial or ethnic nondiscrimination, which is covered in more detail in the separate nondiscrimation rulemaking.
A paragraph that made me smile, reading the July 2022 physician fee schedule proposed rule for CY2023.
Click to enlarge.
Each year, sometime between June and October, CMS releases a detailed database of all physician paid claims for the calendar year, 18 months prior. Accordingly, in July 2022, CMS has released this granular data for CY2020.
Find the database here. It's a cloud database (click VIEW DATA) which can be sorted by doctor name, NPI, specialty, state, CPT code, or more, and any combination of the above. For example, you could get all the labs that billed Medicare Part B for 81162 BRCA testing in 2020, or all the providers who did cataract surgery.
For example, if you look up CPT codes 81410, 81411 for aortic genetics, 40% of the US services were paid to one lab, in Lafayette, CO. One can download all the lab codes by every lab and provider (quite a large file) or all the genetic codes 81000-81600, which are quite manageable in Excel.
Back in May 2022, I may have been one of the first to publicly comment, that HHS had stripped emails and phone numbers from its longstanding employee web directory.
http://www.discoveriesinhealthpolicy.com/2022/05/has-famous-hhs-directory-suddenly.html
As of July 28, 2022, the emails and telephones seem to be back. Note that you search for a name, then get a listing of that name (or matching names), and when you "click" on the last name, you get a new page with more information.
https://directory.psc.gov/employee.htm
Back in 2017, my webmaster and I set up a link on Discoveries in Health Policy (upper right) that lets you either subscribe (1) via a blog reader, OR, (2) by email feed. Google has dropping its years-old Feedburner services (here, here.) Email feeds to my blog, for several hundred subscribers, may have stopped 7/22/2022.
I believe I've set up an account with the Feedblitz company to manage email lists.
The interaction between a laboratory's specimen collection reimbursement to providers, and, anti-kickback laws, is a complex one. I am not an attorney, but I have always heard that "fair market value" was one of the key policy considerations.
A new OIG advisory opinion has been posted (OIG 22-09) which raises some important concerns or subtleties around fair market value and other parts of the safe harbor concepts.
Find the original opinion here:
https://oig.hhs.gov/documents/advisory-opinions/1031/AO-22-09.pdf
See discussions at:
Even more than it used to be, Medicare LCDs are appearing which closely tag coverage to guidelines. The NGS MAC tags BRCA sequencing coverage to "the most recent version of the NCCN guideline" for that. MolDx recently released an LCD for hereditary cancer risk testing (such as BRCA or Lynch syndromes), which attributes current coverage policy to outside guidelines. MolDx and Novitas attribute pharmacogenetic testing coverage to external guidelines from FDA or a PGx organization called CPIC. Finally, Novitas MAC recently released a proposed LCD for oncology that essentially locks coverage to current guidelines from NCCN or two other databases.
So what's in guidelines? See the most recent ASCO guideline for biomarkers for systemic therapy selection in advanced breast cancer. It was released June 27, 2022 as Henry et al. Find it here:
https://ascopubs.org/doi/full/10.1200/JCO.22.01063
I'll quote the abstract further below. If you have a NEW test this year (say, a protein or RNA expression test) to select chemotherapy, it won't be in the guideline, which may count against you at coverage time where the LCDs very specifically point to guidelines as the authorities for coverage.
ASCO also updated guidelines in June 2022 for risk biomarkers for adjuvant therapy (here).
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Henry et al:
Candidates for a regimen with a phosphatidylinositol 3-kinase inhibitor and hormonal therapy should undergo testing for PIK3CA mutations using next-generation sequencing of tumor tissue or circulating tumor DNA (ctDNA) in plasma to determine eligibility for alpelisib plus fulvestrant.
If no mutation is found in ctDNA, testing in tumor tissue, if available, should be used.
Patients who are candidates for poly (ADP-ribose) polymerase (PARP) inhibitor therapy should undergo testing for germline BRCA1 and BRCA2 pathogenic or likely pathogenic mutations to determine eligibility for a PARP inhibitor.
There is insufficient evidence for or against testing for a germline PALB2 pathogenic variant to determine eligibility for PARP inhibitor therapy in the metastatic setting.
Candidates for immune checkpoint inhibitor therapy should undergo testing for expression of programmed cell death ligand-1 in the tumor and immune cells to determine eligibility for treatment with pembrolizumab plus chemotherapy.
Candidates for an immune checkpoint inhibitor should also undergo testing for deficient mismatch repair/microsatellite instability-high to determine eligibility for dostarlimab-gxly or pembrolizumab, as well as testing for tumor mutational burden.
Clinicians may test for NTRK fusions to determine eligibility for TRK inhibitors.
There are insufficient data to recommend routine testing of tumors for ESR1 mutations [estrogen receptor], for homologous recombination deficiency, or for TROP2 expression to guide MBC therapy selection.
There are insufficient data to recommend routine use of ctDNA or circulating tumor cells to monitor response to therapy among patients with MBC.
July issues of JAMA and Annals of Internal Medicine each brought out several articles with new insights for diagnostics.
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Since Fall 2021, JAMA has published a surprisingly extensive series of articles on diagnostics and diagnostics excellence. Newly, we have:
Sarma et al. (2022) Achieving Diagnostic Excellence for Cancer: Symptom Detection as a Partner to Screening. JAMA July 18 online. Here.
Sarma et al. describe that only a limited number of cancers have widely endorsed screening tests (cervical, breast, colon, and more recently and less successfully, lung). Yet even in these cancers only a minority are detected by population screening. They describe programs in UK and elsewhere looking at early symptom work-up and intervention.
Reyna et al. (2022) Rethinking Algorithm Performance Metrics for Artificial Intelligence in Diagnostic Medicine. JAMA 328:329. Here.
Reyna et al. describe cases where special metrics have been weighted to maximize test usefulness during test comparisons. For example, a sepsis detection test had different weights for penalties when wrong diagnoses were false positives vs false negatives. This goes beyond classic simple metrics (sensitivity, specificity, area under curve) and merges evaluation with specific use cases. Another example was in cardiology AI diagnoses, where "false" diagnoses that led to the same workup pathway as correct ones, had smaller penalties. (Related, see Persson on machine learning ICU algorithms for sepsis, here, and another "rich content" evaluation of algorithms by Cerrato et al. here.)
Turning to Annals of Internal Medicine:
Burke et al. (2022) The Challenge of Variants of Unknown Significance. AIM 175:994. Here.
The authors summarize, "the high prevalence of rare and novel variants in the human genome points to VUSs as an ongoing challenge. Additional strategies can help mitigate the potential harms of VUSs, including testing protocols that limit identification or reporting of VUSs, subclassification of VUSs according to the likelihood of pathogenicity, routine family-based evaluation of variants, and enhanced counseling efforts. All involve tradeoffs, and the appropriate balance of measures is likely to vary for different test uses and clinical settings. Cross-specialty deliberation and public input could contribute to systematic and broadly supported policies for managing VUSs."
Lehmann et al. (2022) Ethical Considerations in Precision Medicine and Genetic Testing in Internal Medicine Practice: A Position Paper From the American College of Physicians. AIM here.
The authors summarize, "Whether or not to use genetic tests or adopt technologies such as genome sequencing in clinical care and, if so, when and how to do so needs careful consideration. This paper focuses on the use of precision medicine and genetics in the practice of general internal medicine, where patients may be at increased risk for a heritable condition, may need a drug associated with a known pharmacogenomic variant, or may have a cancer diagnosis for which genetic information may guide treatment decisions. This position paper is intended to complement and provide more specificity to the guidance outlined in the American College of Physicians (ACP) Ethics Manual, which identifies a number of issues associated with precision medicine..."
Lee et al. (2022) QUAPAS: An Adaptation of the QUADAS-2 Tool to Assess Prognostic Accuracy Studies. AIM 175:1010.
One of the world experts in diagnostics tests and theory is Patrick Bossuyt of the University of Amsterdam (here). Here, the Dutch team adapts a major diagnostic test guideline, QUADAS (QUADAS-2) for prognostic test accuracy: QUAPAS with a "p".
QUADAS-2. see here, and here. See also QUADAS-C, for "Comparisons" of diagnostic tests, here.
(See also my blog on MolDx's newly released checklist for prognostic tests, here.)
There are a lot of issues with conventional low-voltage evaluation metrics for prognostic tests.
Let me briefly note a July 18, 2022, press release from Natera, announcing it has obtained bladder cancer coverage for its Signatera liquid biopsy test, from the MolDx program. Natera notes that it believes this is the first expansion in coverage under a MolDx LCD for minimal residual disease (MRD), which was published in December 2021.
Workers in this space should note that the coverage in the second half of 2022 appears to be based principally on 2019 and 2021 publications, which presumably Natera got to MolDx quickly. One study had 68 patients with over 600 plasma samples. The other study had nearly 600 patients with biosamples from an RCT. In short, Moldx coverage is not fast, not cheap, and not easy, even for one of the most experienced companies.
I'll put the link to the Natera press below, and quote the press release after the break.
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On July 25, 2022, HHS released a new proposed rule for non-discrimination in healthcare settings, including in relationship to sexual orientation and gender identity. First the facts and links, then, more about the back-story.
Facts and Links
See the HHS press release here:
See the new proposed rule here (308pp):
https://www.hhs.gov/sites/default/files/section-1557-nprm.pdf
SEE THE FINAL PAGINATED VERSION, FED REG, AUG 4, 2022. 87 FR 47824-920, comments to October 3. Here.
The press release quotes Executive Orders under Biden such as one on his first day in office on gender discrimination (here). In general, the new regulations are framed by the Biden administration as amplifying and specifying rights that are already created by the Affordable Care Act at its Section 1557 (HHS web page and fact sheets here.) An extensive section discussed the legislative and regulatory history, the prior publication [Trump administration] of CY2020, and recent court cases such as definitions of sex including gender identity.
See news coverage at Healthcare Dive here. Foley Hoag here. McDermott here. (McDermott back story on LGBT in 2020 here). AAMC here. See general comments on the topic at WSJ here.
An interesting section (p 176ff) bans clinical algorithms that cause discrimination in health care services based on inputs including sex and age, as well as race. See more in my July 29 blog.
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Back Story
There's more back story.
In 2016, the Obama administration released a "double hitter" proposed rule, that covered gender and other discrimination in hospitals in part, and also, proposed a new requirement for hospital antibiotic stewardship programs (ASP). 81FR39447.
In 2019, the 2016 proposed rule(s) were set to expire uncompleted. Due to effective communications from stakeholders, the sunset of the 2016 proposed rule was delayed just before the sunset occurred (7/11/2019, 84FR27069). Then, a few months later, CMS issued final regulations in September 2019 regarding the hospital antibiotic stewardship programs (ASP). 84FR51732. HHS generally took the position that the LGBT aspects of the regulations from 2016 were redundant to other federal laws, to the extent they were needed at all. The ASP rules were finalized more or less as proposed in 2016.
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By coincidence, CMS just released final instructions to hospitals on the 2019 ASP rules this month, in July 2022, here.
This blog discusses several new or recent resources.
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Essay:
A few months before the COVID pandemic, CMS updated national requirements for antibiotic stewardship programs in hospitals, finalizing the relevant regulations in the Federal Register (84FR51732 here). After that publication in September 2019, a few months later, CMS included the regulations themselves in the State Operations Manual, which serves both as a guide to hospital duties and as a handbook for inspectors. Here. However, CMS hadn't yet done what it normally does, to provide an amplified practical implementation guide of the regulations themselves.
Now in July 2022 has CMS published a 22-page handbook for how hospitals can implement the ASP in the 2019 regulations. Find the instructions to hospitals and inspectors online here:
https://www.cms.gov/files/document/qso-22-20-hospitals.pdf
Paper Clip This, to That:
The CMS guidance hardly mentions the word "laboratory" which I found puzzling. However, the guidance frequently refers to implementing external, authoritative guidelines, and fortunately we have just that from CDC. See the August 2020 edition of "Key Activities and Roles for Microbiology Laboratory Staff in Antibiotic Stewardship Programs." It's a critical 5 page addition to the 22 page CMS implementation guidance just published. HERE.
But Wait, There's More
Pair this with some important documents from CDC on diagnostics and ASP and sepsis.
And, finally published in 2022, see Curren et al. This is the result of a December 2019 (pre pandemic!) workshop held at CDC on diagnostics and antibiotic resistance and sepsis, meet report by Curren et al. Find it in Clin Infect Disease, here.
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I assume that soon the 22 page CMS update on ASP in hospitals, will be integrated into the master 600 page hospital handbook here.