On November 30, 2017, CMS released a draft blanket coverage determination for the Foundation Medicine F1CDx test for all cancer patients with tumors for which it is on-label, expanding on a rolling basis with label expansion.
There are some unusual follow-on aspects of the decision. For example, if the F1CDx covers one PMA gene in a certain cancer, and even if that gene is already known positive or negative based on the prior IVD that F1CDx is itself based on, F1CDx is still covered. (Let's say for a million patients at $3000, or $3B). This seems to imply F1CDx has some value beyond its on-label genes. However, neither FDA nor CMS ever broached that conclusion. Also puzzlingly, there will be some cancers where the F1CDx points only to off-label drugs for 95% of patients (especially if common mutations like EGFR have already been filtered out by prior testing). Despite requiring CED for all other testing approaches, the NCD doesn't require (or misses the opportunity to require) any form of records, tracking or CED for this huge cancer population, as long as their pathway to off-label drugs was via "failing to have an on-label drug on the F1CDx test."
Everybody "Defined-Away" the Clinical Utility of Large Panels
There has been huge debate in the US and world oncology literature on the value of large gene panel tests, and Vinay Prasad of OHSU has publicly protested that the F1CDx coverage decision is premature (here).
In succession, MolDX, FDA, and CMS defined away this question in their reviews.
MolDx Decision
The MOLDX LCD for FMI F1 (L36198) doesn't state that 300- or 400 gene panel tests are medically necessary. Rather, the LCD discusses that for one or two identified genes, like EGFR, if you do an FDA IVD point mutation test, it will pick up certain common mutations, and if you sequence that known PMA biomarker gene, you will pick up several extra actionable mutations (e.g. 17% more). What is done with, or why, regarding the other 300 or 400 genes that the test reports simply isn't brought into the question.
FDA Decision
Go to the FDA F1CDx webpage (P170019, here) and look up the safety and effectiveness review document. In the pivotal risk-benefit determination, page 55, section C, FDA states that "F1CDx assay has demonstrated non inferiority to companion diagnostics [reviewed in Section X] and therefore, does not introduce additional risks above [the] other approved devices." FDA has been able to define away any actions with any of the additional several hundred genes since they are not on-label claims, so, as judges say, FDA need not reach or speculate towards any conclusion on the large panel, in order to approve F1CDx.
FDA also comments that the F1CDx was not referred to an advisory panel because all questions or issues in the F1 PMA duplicate information already reviewed (e.g. the prior review of the single EGFR gene for erlotinib.)
CMS Decision
Finally, while CMS's NCD is 40 to 60 pages long, depending how you print it, the pivotal decision for coverage of F1CDx at the end is extremely brief, and merely states because F1CDx includes PMA on label genes, F1CDx is "reasonable and necessary." Any emergent or associated collateral risks or benefits, or whether the test "meets but does not exceed the patient's need" (a traditional CMS metric), simply don't enter into the final decisional sentences.
Is This Good Or Bad?
I mostly see the NCD as having a lot of weird consequences that people will look back in in 3, 6 or 12 months and say, "Wow." For example, leukemia seems to be under the NCD (it's oncology), but there are no PMA gene panel tests, and no 510(k) tests, so coverage of genetic testing is available only in NCI trials, and for the most common genes and drugs, those trials won't even exist any more. (Alternately, leukemia patients must be in C.E.D., for which CMS mandates RECIST imaging testing for participation, which leukemia patients can't do, so they can't get the C.E.D. arm.) Another "wow" is that very soon, massive numbers of Medicare patients without any on-label genetic results will get lots and lots and lots of off-label genetic results, for which no plan is made.
My main point is that one would think that along the pathway to this decision, CMS or FDA would have "had to have" looked at clinical utility (or net risk benefit) of large gene panel tests, and they didn't, at least not in the pivotal decisional parts of their documents.
____
I posted a very informal, freehand summary of the FDA concordance studies for F1 CDx, here.
Tuesday, January 9, 2018
Sunday, January 7, 2018
Very Brief Blog: Tracking JP MORGAN HEALTHCARE CONFERENCE
The JP Morgan Healthcare conference 2018 (36th Annual) is meeting this week in San Francisco, with satellite events Sunday, January 7, and the main invitation-only conference running all week at the St Francis Hotel Convention Center at Union Square.
Even the agenda of the conference is not readily available. JP Morgan publishes a very short website for JPMHC18 here, and JP Morgan Global publishes a somewhat longer website here. (IT has a rather curt FAQ section, such as: Q: Where can I get an agenda? A: Agendas are available only to attendees.")
JPMorgan seems to endorse #JPMHC18 as the official Twitter hashtag, although there is also a lot of usage of #JPM18 too.
See a webfeed on Twitter for #JPMHC18 by clicking here. (Hardcore Twitter fans that also want to see #JPM18 can find it here.)
There is a long list of activities (including listing for many marked as "private"like the Harvard Business School JPM recewiption) at: JPM.HEALTH, here.
Update.
From the public INVIDIOR.COM investor web site, here, there is a public link to the JP Morgan webpage for agenda and links to most all presentations on the conference as archived streaming audio or video, here. Email registration required for entry.
Even the agenda of the conference is not readily available. JP Morgan publishes a very short website for JPMHC18 here, and JP Morgan Global publishes a somewhat longer website here. (IT has a rather curt FAQ section, such as: Q: Where can I get an agenda? A: Agendas are available only to attendees.")
JPMorgan seems to endorse #JPMHC18 as the official Twitter hashtag, although there is also a lot of usage of #JPM18 too.
See a webfeed on Twitter for #JPMHC18 by clicking here. (Hardcore Twitter fans that also want to see #JPM18 can find it here.)
There is a long list of activities (including listing for many marked as "private"like the Harvard Business School JPM recewiption) at: JPM.HEALTH, here.
Update.
From the public INVIDIOR.COM investor web site, here, there is a public link to the JP Morgan webpage for agenda and links to most all presentations on the conference as archived streaming audio or video, here. Email registration required for entry.
Tuesday, January 2, 2018
Very brief blog: MobiHealthNews Summarizes 224 DHealth Investments ($5B)
In a year-end article for 2017, MobiHealthNews summarizes 224 investments in digital health, ranked in tiers ($100M or more; $50M-100M, etc). Each investment is briefly summarized and carries a link to more information. Online here.
Investments tallied $1.3B in Q1, $2.6B in Q2, and about $550M in Q3 and Q4 each.
Investments tallied $1.3B in Q1, $2.6B in Q2, and about $550M in Q3 and Q4 each.
 |
| click to enlarge |
Tuesday, December 26, 2017
NEW 20 PAGE WHITE PAPER ON CMS NEXT GEN SEQUENCING NCD
On November 30, 2017, CMS released a 65-page, 45,000 word NCD proposing an entirely new policy approach to all uses of next generation sequencing in oncology.
I've had the chance to talk to a number of stakeholder groups and read the NCD several times, as well as underlying documents such as the FDA approval review for FMI F1 CDx.
Here, I post a 20 page (7000 word) white paper on the NCD and its potential implications.
Version: 03, January 2, 2018. * HERE * - click arrow upper right to download.
This white paper was downloaded 450 times (December 25-January 5). More after the break.
I've had the chance to talk to a number of stakeholder groups and read the NCD several times, as well as underlying documents such as the FDA approval review for FMI F1 CDx.
Here, I post a 20 page (7000 word) white paper on the NCD and its potential implications.
Version: 03, January 2, 2018. * HERE * - click arrow upper right to download.
This white paper was downloaded 450 times (December 25-January 5). More after the break.
Sunday, December 24, 2017
Friday, December 22, 2017
Very Brief Blog: J Mol Dx Article on History of Genomic Reimbursement & Coding
New online at Journal of Molecular Diagnostics (included with Association for Molecular Pathology membership). Hsiao, Mansukhani, Carter, and Sireci of Columbia University have written an in depth study of actual changes in reimbursement (and coverage) in their molecular laboratory as policy, coding, and fee schedules have rapidly evolved in recent years.
The in press manuscript is online here. Don't miss the interesting graphics from page 20 forward.
ABSTRACT
Changes in coding and coverage create uncertain reimbursement environment for molecular pathology laboratories.
We analyzed our experience with two representative molecular oncology tests: a T-cell receptor (TCR) beta rearrangement test and a large (467 gene) cancer next-generation sequencing panel the Columbia Combined Cancer Panel, CCCP.
Prior to 2013, the TCR beta test was coded using “stacked” current procedural terminology codes and subsequently transitioned to a tier 1 code. CCCP was coded using a combination of tier 1 and 2 codes until 2015, when a new Genomic Sequencing Procedure code was adopted. A decrease in reimbursement of 61% was observed for the TCR beta test upon moving from stacking to tier 1 codes. No initial increase in total rejection rate was observed but a subsequent increase in rejection rates in 2015 and 2016 was noted.
The CCCP test showed a similar decrease (48%) in reimbursement following the adoption of the new genomic sequencing procedure code and was accompanied by a sharp increase in rejection rates both on implementation of the new code and over time.
Changes in coding can result in substantial decreases in reimbursement. This may be a barrier to patient access due to the high cost of molecular diagnostics. Revisions to the molecular code set will continue. These findings help laboratories and manufacturers prepare for the financial impact and advocate appropriately.
Sample graphic:
The in press manuscript is online here. Don't miss the interesting graphics from page 20 forward.
Changes in coding and coverage create uncertain reimbursement environment for molecular pathology laboratories.
We analyzed our experience with two representative molecular oncology tests: a T-cell receptor (TCR) beta rearrangement test and a large (467 gene) cancer next-generation sequencing panel the Columbia Combined Cancer Panel, CCCP.
Prior to 2013, the TCR beta test was coded using “stacked” current procedural terminology codes and subsequently transitioned to a tier 1 code. CCCP was coded using a combination of tier 1 and 2 codes until 2015, when a new Genomic Sequencing Procedure code was adopted. A decrease in reimbursement of 61% was observed for the TCR beta test upon moving from stacking to tier 1 codes. No initial increase in total rejection rate was observed but a subsequent increase in rejection rates in 2015 and 2016 was noted.
The CCCP test showed a similar decrease (48%) in reimbursement following the adoption of the new genomic sequencing procedure code and was accompanied by a sharp increase in rejection rates both on implementation of the new code and over time.
Changes in coding can result in substantial decreases in reimbursement. This may be a barrier to patient access due to the high cost of molecular diagnostics. Revisions to the molecular code set will continue. These findings help laboratories and manufacturers prepare for the financial impact and advocate appropriately.
Sample graphic:
 |
| click to enlarge |
Thursday, December 21, 2017
Health Executive Adam Boehler Might Head CMMI Next
According to a tweet from PoliticoPro, health executive Adam Boehler might become the new head of the billion dollar Center for Innovation at Medicare (the CMMI). Tweet here.
Boehler's Linked In is here. He's also listed at Bloomberg biographies here, and his profile as CEO of Landmark Health is here.
Boehler comes out of the Wharton School and has had both venture capital and operational roles. He was previously involved with a 25-lab network with 3000 employees, aLabs. According to Bloomberg, he's Chair and President at Landmark; Executive Chairman at Avalon Health.
Landmark Health, where he's currently CEO, is designed to provide superior, next-generation home health care and home based medical care to patients "24/7/365." Earlier this month, Landmark recently hired Christopher Goldsmith (of Optum and with an INSEAD MBA) as President.
Previous CMMI director Dr Patrick Conway stepped down in mid-year to join North Carolina BCBS. CMMI is rebooting itself for new directions under the new administration.
Boehler's Linked In is here. He's also listed at Bloomberg biographies here, and his profile as CEO of Landmark Health is here.
Boehler comes out of the Wharton School and has had both venture capital and operational roles. He was previously involved with a 25-lab network with 3000 employees, aLabs. According to Bloomberg, he's Chair and President at Landmark; Executive Chairman at Avalon Health.
Landmark Health, where he's currently CEO, is designed to provide superior, next-generation home health care and home based medical care to patients "24/7/365." Earlier this month, Landmark recently hired Christopher Goldsmith (of Optum and with an INSEAD MBA) as President.
 |
| click to enlarge |
Previous CMMI director Dr Patrick Conway stepped down in mid-year to join North Carolina BCBS. CMMI is rebooting itself for new directions under the new administration.
Feds Release Surprisingly Affordable Report on Excessive Drug Prices
On November 30, 2017, the National Academy of Medicine released a free 200 page report on the problem of excessive drug prices.
Drug costs have been a concern for generations; Senator Kefauver of Tennessee began hearings on drug price-fixing when he was told (in 1955!) that two different antibiotics at his corner pharmacy both cost exactly $3. (This vendetta eventually transformed and morphed into the Kefauver FDA amendments of 1963).
The NAM press release is here and the PDF report is available here. It comes with a one hour panel media presentation as archived video, here.
Coverage at:
This National Academies project is different than a mid November GAO report on drug profits compared to R&D spending; see the 70 page GAO report here and the Endpoints blog on it here.
Bonus reading.
For Bloomberg December as "Diabetes as the Messiest Drug Market," here. Also from Bloomberg in December, "FDA Targets Insulin" for excessive prices, here. Fpr a summer article at Bloomberg on "Crazy Math Behind Drug Prices," here.
Drug costs have been a concern for generations; Senator Kefauver of Tennessee began hearings on drug price-fixing when he was told (in 1955!) that two different antibiotics at his corner pharmacy both cost exactly $3. (This vendetta eventually transformed and morphed into the Kefauver FDA amendments of 1963).
The NAM press release is here and the PDF report is available here. It comes with a one hour panel media presentation as archived video, here.
Coverage at:
This National Academies project is different than a mid November GAO report on drug profits compared to R&D spending; see the 70 page GAO report here and the Endpoints blog on it here.
For Bloomberg December as "Diabetes as the Messiest Drug Market," here. Also from Bloomberg in December, "FDA Targets Insulin" for excessive prices, here. Fpr a summer article at Bloomberg on "Crazy Math Behind Drug Prices," here.
CMS Extends Comment Period on NGS/Cancer Proposed NCD
CMS has extended the comment period to January 17, 2017, on the currently debated National Coverage Determination for all uses of next generation sequencing in cancer. The NCD provides coverage only for PMA-approved tests used on-label in the relevant cancers. The NCD would cover patients who are part of clinical studies (coverage with evidence developments) for other uses of PMA- or 510(k)-approved NGS tests.
The tracking and dates page is here. The NCD is here.
The tracking and dates page is here. The NCD is here.
 |
| Comment deadline has been revised (old, Dec 29, new Jan 17) |
Tuesday, December 19, 2017
Regulatory Nerd Corner: Medicare Review Board Decision Narrows Scope of ALJ Review of LCDs
A section of law called BIPA 522, more than a decade old, gives a channel whereby a beneficiary can appeal an entire LCD rather than just his personal claim. The decision is fast-tracked to an Administrative Law Judge (ALJ).
In past cases, ALJs have ruled that there can be "constructive LCDs" - for example, if a contractor says in an Article that Service XYZ is not reasonable and necessary and is non-covered, that may not be formally called an LCD by its MAC author, but it is a de facto LCD, and can be appealed through the BIPA 522 channel.
A 2017 Medicare review board case reversed an ALJ who had broadly construed his ability to call something a constructive LCD based on a reasonable and necessary decision. In the case, a DME MAC had ruled that continuous glucose monitors were "not a benefit category" because they were "precautionary" to check for low glucose levels. The ALJ ruled this was equivalent to saying they were not reasonable and necessary and found the CGM should be covered. CMS escalated the case to a panel of review judges, who ruled that the decision of the MAC was a "benefit category decision" and therefore not accessible by the LCD review process, which is only for "reasonable and necessary" decisions.
The potential adverse affect is for devious MACs to couch decisions in articles rather than in LCDs and switch to terms like "experimental and investigational" or as "precautionary" or as "benefit category decisions" with an eye to avoiding the textual keywords that would allow review by ALJs under the LCD review channel. I never understood the reasoning around "precautionary" - all glucose tests are precautionary for an abnormal glucose finding, INR tests in warfarin patients are "precautionary" for an abnormal INR finding. An MRI in a unilateral headache patient could be styled as "precautionary" for discovering if he has a brain tumor, and so on.
The particular decision about CGMs is of historic interest now as later CMS decisions allow coverage of some CGMs.
In past cases, ALJs have ruled that there can be "constructive LCDs" - for example, if a contractor says in an Article that Service XYZ is not reasonable and necessary and is non-covered, that may not be formally called an LCD by its MAC author, but it is a de facto LCD, and can be appealed through the BIPA 522 channel.
A 2017 Medicare review board case reversed an ALJ who had broadly construed his ability to call something a constructive LCD based on a reasonable and necessary decision. In the case, a DME MAC had ruled that continuous glucose monitors were "not a benefit category" because they were "precautionary" to check for low glucose levels. The ALJ ruled this was equivalent to saying they were not reasonable and necessary and found the CGM should be covered. CMS escalated the case to a panel of review judges, who ruled that the decision of the MAC was a "benefit category decision" and therefore not accessible by the LCD review process, which is only for "reasonable and necessary" decisions.
- I describe in more detail here and provide links.
- DME benefit category decisions can have close overlap with reasonable and necessary decisions because categorizing something as DME invokes some steps that involve its medical use and purpose.
The potential adverse affect is for devious MACs to couch decisions in articles rather than in LCDs and switch to terms like "experimental and investigational" or as "precautionary" or as "benefit category decisions" with an eye to avoiding the textual keywords that would allow review by ALJs under the LCD review channel. I never understood the reasoning around "precautionary" - all glucose tests are precautionary for an abnormal glucose finding, INR tests in warfarin patients are "precautionary" for an abnormal INR finding. An MRI in a unilateral headache patient could be styled as "precautionary" for discovering if he has a brain tumor, and so on.
The particular decision about CGMs is of historic interest now as later CMS decisions allow coverage of some CGMs.
My Article on "DIGITAL GENOMICS" Is UP at Journal of Precision Medicine
Over the past year, I produced a white paper and gave several talks and chaired two panels on "Digital Genomics." A corresponding article is now online (open access) at Journal of Precision Medicine.
See the journal homepage here. See the PDF article here.
The article has two parts. The first part talks about labs that are creating an elaborate digital ecosystem around the traditional molecular lab services - "Lab 3.0." The second part talks about companies that are being established without any wetlab, and dedicated to providing digital genomic services like state of the art outsourced software, analytics, and bioinformatics pipelines.
This continues to be an active area of investment, e.g. a $58M investment in DNANexus was announced on January 2, here.
See the journal homepage here. See the PDF article here.
The article has two parts. The first part talks about labs that are creating an elaborate digital ecosystem around the traditional molecular lab services - "Lab 3.0." The second part talks about companies that are being established without any wetlab, and dedicated to providing digital genomic services like state of the art outsourced software, analytics, and bioinformatics pipelines.
 |
| click to enlarge |
Monday, December 18, 2017
Very Brief Blog: FDA Releases Two Draft Guidances re Biomarkers for Rare Subsets and IDE IVDs in Clinical Trials
One December 18, 2017, the FDA released two draft guidances (both open for 60 days comment) on precision medicine.
- The FDA's press release is here.
- Coverage at Genomeweb here.
- The FIRST guidance, on biomarkers for rare disorders in clinical trials, is here (8pp).
- This codifies some of the principles used in the May 2017 approval of Keytruda in all solid cancers with high MSI (here). The pivotal labeled study involved 90 colorectal cancer patiens and 59 other patients, such as 11 biliary, 9 gastric, and as few as 1 or 2 for a number of cancers.
- It was far from conventional "proof" that Keytruda works in "all" solid cancers.
- This guidance is paired with and timed to an FDA article in Nat Rev Drug Devel (12/2018) by Schuck, Pacanowski, Woodcock, and Zineh, here. The FDA guidance and the Schuck et al. article are mutually explanatory.
- The SECOND guidance, on requirements for Investigational Device Exemption when biomarkers are used in clinical trials, is here (26pp). For example, an FDA approved KRAS biomarker used off label in a different tissue trial may require IDE.
- To my eye FDA has already offered this rigorous view of the need for IDE status in clinical trials, but FDA pointedly notes that perhaps not all IRBs and investigators got the point.
- FDA immediately tags this upgraded regulatory enforcement by adding it is looking to "streamline the review of oncology products and [oncology] IVDs" through additional guidance and in the near future.
Regulatory Nerd Corner: The Regulation for the MSK IMPACT test does not exist in the CFR
(Updated)
For regulatory nerds, the MSK IMPACT test, recently cleared by the FDA as a de novo Class II test, has a product code (PZM) and a regulatory classification, 21 CFR 866.6080.
The Class II decision memorandum is here (DEN170058). The product code PZM webpage at FDA is here.
____
FDA has a page on procedures for Direct Final Rulemaking, but it is predicated on publication in the Federal Register, which I've been unable to find for 866.6080. Here.
FDA Commissioner Gottlieb was sworn in May 11, 2017.
For regulatory nerds, the MSK IMPACT test, recently cleared by the FDA as a de novo Class II test, has a product code (PZM) and a regulatory classification, 21 CFR 866.6080.
The Class II decision memorandum is here (DEN170058). The product code PZM webpage at FDA is here.
- However, the US Code of Federal Regulations or CFR has no regulation under 21 CFR 866.6080. Regulations stop at 866.6060. Here.
- Yet, the FDA has a webpage saying that 866.6080 was created on April 1, 2017.
- (Ha ha? Not only was that April Fool's Day, but it was a Saturday, when the Fed Reg doesn't publish). Here.
- In short, the regulation as numbered on the FDA CFR webpage at FDA fail to foot to any actual regulation in the real Code of Federal Regulations, which would be here.
The solution to the puzzle is not entirely satisfying, but here it is. In order to clear a product as a de novo 510(k) product, there has to be a classification order which means there has to be a 510(k) category to put the product "into" such as 21 CFR 866.nnnn. (See the FDA guidance on de novo classification processes, October 2017, here.) So yes, the FDA internally created 21 CFR 866.6080 (sic), but will (eventually) publish an article in the Federal Register creating that regulation, at which point the new category will appear in the national CFR that everyone can access. In the guidance (UCM080197), FDA says (a) it will issue the order to the sponsor and classify the device in that letter, and (b) "we will then publish a final order in the Federal Register, etc. So it gives the appearance that the "regulation" exists on the FDA website before it appears in the FR or CFR. And in this case, the FDA regulatory creation is dated April 2017, the Sloan Kettering first example of a product is November 2017, and the Federal Register publication will be December 2017 or in 2018.
I suppose a Sherlock Holmes FDA sleuth could have figured out that something big was up if they tracked the sudden mystery appearance of 866.6080 on the FDA website as a Class II gene panel test last spring, but he wouldn't have known it would contain oncology genes that are otherwise PMA level CDx biomarkers.
I suppose a Sherlock Holmes FDA sleuth could have figured out that something big was up if they tracked the sudden mystery appearance of 866.6080 on the FDA website as a Class II gene panel test last spring, but he wouldn't have known it would contain oncology genes that are otherwise PMA level CDx biomarkers.
 |
| FDA.gov web page for the regulation, 21 CFR 866.6080 ("Created April 1") |
 |
| Actual 21 CFR 866.nnnn Section at Federal CFR (Dec 18 2017) |
FDA has a page on procedures for Direct Final Rulemaking, but it is predicated on publication in the Federal Register, which I've been unable to find for 866.6080. Here.
FDA Commissioner Gottlieb was sworn in May 11, 2017.
Very Brief Blog: FDA Posts the Approval Documentation for Foundation CDX
UPDATE - MONDAY - DECEMBER 18 2018
FDA HAS POSTED APPROVAL PDF's ON FMI CDX
See also all documents in one cloud zip file (Dec 18):
The Approval Order is 5pp; the Safety & Effectiveness document is 58pp; the Labeling is 43 pp.
Four conditions of approval include (1) "clinical concordance data to support the performance of your device within the appropriate clinical contexts." [?] (2) Response for NSCLC patients with EGFR T790M mutation mutant allele frequency (MAF) < 5%. (3) "Provide additional results from clinical samples to establish the analytical performance characteristics "for all variant types and genomic signatures." This includes MSI, TMB, CNA, rearrangements. (4) Software documentation for: validating and implementing software design changes.
The FDA specifically segregates "test output" or reporting into Category 1 CDx claims, Category 2 output of genes with "evidence of clinical significance," and Category 3 claims of "potential" clinical significance (the latter including e.g. animal studies or other rationales). See FDA explanation here. (510K gene panels have only Category 2&3 claims.)
The test runs on an Illumina HiSeq 4000. It uses paraffin block inputs and must have 55 ng of genomic DNA. The S&E documentation includes a "Table 5" which lists all FDA approved CDx (in any format, e.g. FISH) that parallels a CDx gene on the FMI label. Table 7 compares concordance of "F1 LDT" and "F1 CDX" (it's high.) There are many tables of comparisons to prior PMA tests (therascreen, cobas, etc). The product was not referred to an advisory panel "because the PMA substantially duplicates information previously reviewed by the panel." All statistics were based on "non inferiority testing."
Since the device was classified as a Breakthrough Device, the FDA's review expectations included "a balance of pre and post market data." The FDA concludes that because F1 CDX was "non inferior" to existing CDx tests, it "does not introduce additional risks." (Thus the reporting of Category 2 and 3 results, unavailable from prior single CDx's, were seen as not being germane to additional risks.) FDA concludes: "The probable benefits outweigh the risks." [Quotes from S&E document, P170019B.)
_____
FMI's own FMI CDX webpage is here.
The FDA specifically segregates "test output" or reporting into Category 1 CDx claims, Category 2 output of genes with "evidence of clinical significance," and Category 3 claims of "potential" clinical significance (the latter including e.g. animal studies or other rationales). See FDA explanation here. (510K gene panels have only Category 2&3 claims.)
The test runs on an Illumina HiSeq 4000. It uses paraffin block inputs and must have 55 ng of genomic DNA. The S&E documentation includes a "Table 5" which lists all FDA approved CDx (in any format, e.g. FISH) that parallels a CDx gene on the FMI label. Table 7 compares concordance of "F1 LDT" and "F1 CDX" (it's high.) There are many tables of comparisons to prior PMA tests (therascreen, cobas, etc). The product was not referred to an advisory panel "because the PMA substantially duplicates information previously reviewed by the panel." All statistics were based on "non inferiority testing."
Since the device was classified as a Breakthrough Device, the FDA's review expectations included "a balance of pre and post market data." The FDA concludes that because F1 CDX was "non inferior" to existing CDx tests, it "does not introduce additional risks." (Thus the reporting of Category 2 and 3 results, unavailable from prior single CDx's, were seen as not being germane to additional risks.) FDA concludes: "The probable benefits outweigh the risks." [Quotes from S&E document, P170019B.)
_____
FMI's own FMI CDX webpage is here.
Sunday, December 17, 2017
Very Brief Blog: CMS Published CY2018 Full Final CLFS Fee Schedule
It seems anticlimatic after a hectic year of lab policies, unprecedented volumes of crosswalk decisions, PAMA crises and lawsuits...but in 1H December, CMS published the "final CLFS fee schedule" for CY2018. It's here. Download the zip file to access the CLFS Excel spreadsheet.
CMS has modified the format from prior years. There are no longer 57 pricing localities; there is one national price. All the prices are listed as effective "20180101," so that indicator will be more interesting as the years go by. CMS now uses the letters "N" and "L" to indicate National or Local pricing, while all the codes with an "L" for local (gapfill) pricing are listed as 0.00 dollars. Dollar rates are listed in the format 00072.19, for $72.19. As always, QW stands for Clia Waived (or Qlia Waived?) tests, which have the same price as the standard price.
For additional details, see Transmittal CR10409 (here). That PDF lists, for example, the final pricing choices behind every price that was crosswalked in summer 2017. ("New code 81176 is priced at the same rate as code 81218,"etc etc). New code prices will behave the same as the target code. Meaning: If New Code is priced to a $200 target code that stays level at $200 each year under PAMA, so does New Code. But if New Code is priced to a $200 target code that falls by 10% a year under PAMA rules, so does New Code. By my count 116 codes were crosswalked (many were codes on the CLFS that had no utilization and thus no PAMA pricing).
18 codes enter the 2018 local gapfill process, in this table:
CMS has modified the format from prior years. There are no longer 57 pricing localities; there is one national price. All the prices are listed as effective "20180101," so that indicator will be more interesting as the years go by. CMS now uses the letters "N" and "L" to indicate National or Local pricing, while all the codes with an "L" for local (gapfill) pricing are listed as 0.00 dollars. Dollar rates are listed in the format 00072.19, for $72.19. As always, QW stands for Clia Waived (or Qlia Waived?) tests, which have the same price as the standard price.
For additional details, see Transmittal CR10409 (here). That PDF lists, for example, the final pricing choices behind every price that was crosswalked in summer 2017. ("New code 81176 is priced at the same rate as code 81218,"etc etc). New code prices will behave the same as the target code. Meaning: If New Code is priced to a $200 target code that stays level at $200 each year under PAMA, so does New Code. But if New Code is priced to a $200 target code that falls by 10% a year under PAMA rules, so does New Code. By my count 116 codes were crosswalked (many were codes on the CLFS that had no utilization and thus no PAMA pricing).
18 codes enter the 2018 local gapfill process, in this table:
 |
| 18 Codes are Class "L for Local" Gapfill in 2018 |
Subscribe to:
Posts (Atom)