EPIGENOMICS N Helden (Seite 343)

[Diabolo2018]

Wie gehts denn nun weiter? 2. Monate nun bis zur fixen Entscheidung. Theoretisch könnte die Entscheidung ja auch die nächsten Tage kommen? EPI wird dann Berufung einlegen! Wenn es bei EPI normal läuft, werden die 2 Monate ausgereizt + x! Für EPI wäre es ja gut wenn die Absage bald kommt um somit früher in Berufung zu gehen

[Gekko279]

ECX wollte aus Stroh, Gold spinnen. einige haben an dieses Märchen geglaubt, dabei haben es die Spatzen längst von den Dächern gepfiffen ...

[Mat14]

Man kann nur noch das Büro Inventar versilbern.
Alles nur noch Geldverbrennung. So langsam stellt sich raus , dass alles was Epi in der Pipeline haben soll nichts anderes als heiße Luft ist.

[Gekko279]

Antwort auf Beitrag Nr.: 65.708.502 von keinGeldmehr am 14.11.20 16:09:17

Exact schlägt nochmal in die gleiche Kerbe in die ich bereits geschlagen habe. Und sollte Exact selber einen Bluttest in der Pipeline haben, dürfte klar sein, dass der fortschrittlicher ist, als Procolon. Damit dürfte eindeutig klar sein, Exact hatte und hat nie ein Interesse an ECX gehabt! Das war der letzte Sargnagel. Schade um die 5,5 Mio., die jetzt noch zum Fenster rausgeschmissen werden!

[keinGeldmehr]

Dieser Kommentar ist an Selbstherrlichkeit, Ignoranz nur durch Donald the Trump zu übertreffen. Leider ist die CMS scheinbar mit Exact Typen durchzogen.

[Gekko279]

ohne vorwegzugreifen, wie bewertet ihr die Stellungnahme von Exact?!

Stellungnahme Exact vom 13.11.2020

Comment: RE: Proposed National Coverage Determination for Screening for Colorectal Cancer-Blood-Based Biomarker Tests (CAG-00454N)

Summary:

Exact Sciences Corporation appreciates the opportunity to comment on the proposed national coverage determination (“NCD”) for blood-based colorectal cancer (CRC) screening tests. As a company committed to increasing CRC screening rates and developing our own blood-based CRC screening test, we support the proposed NCD and recommend that CMS establish more specific coverage criteria that balance the benefit of blood-based screening against the potential harm of using a less-accurate test.

Elaborating on the CMS recommendations, we propose the following additional criteria for evaluating Medicare coverage of a blood-based CRC screening assay:

1) CMS should set minimum performance requirements that demonstrate head-to-head non-inferiority to FIT for early-stage CRC and advanced adenoma detection
2) CMS should use recommended tests as benchmarks to inform the covered screening interval, with guidelines as an alternative coverage pathway
3) CMS should require FDA-approval of the assay for front-line, average-risk screening
4) CMS should cover CRC screening beginning at age 45 years or as recommended by major guidelines.
5) CMS should clarify that follow-up colonoscopy to an initial non-invasive test is part of the screening process and a covered preventive service

Detailed Comments:

1) CMS should set minimum performance requirements that demonstrate head-to-head non-inferiority to FIT for early-stage CRC and advanced adenoma detection

We agree with CMS that FIT is the appropriate minimum performance comparator for a blood-based CRC screening test. However, FIT should be the benchmark not only for all-stage CRC sensitivity, but also for early-stage CRC and advanced adenoma (AA) sensitivity, which is the primary benefit of screening.

Given the evidence supporting the clinical utility of FIT (1), any test with equivalent performance metrics would be expected to provide similar clinical benefits. Non-inferiority to FIT would also ensure that any patients switching from a guideline-supported strategy to a new blood-based screening strategy would not be subject to additional harms by way of missed CRC or advanced adenoma.

The effectiveness and clinical utility of any new non-invasive screening test, including blood-based, will be dependent on its ability to detect early stage cancers and precancerous lesions (2,3). Advanced adenoma detection significantly influences the predicted benefits derived from front-line CRC screening modalities (4). Therefore, a blood-based test should demonstrate the ability to detect early stage CRC and AA, at sensitivities similarly non-inferior to FIT. However, the reported early-stage and advanced adenoma detection rates of several blood-based CRC screening tests in development are well below those of established CRC screening tests like FIT (2).

Evidence of non-inferiority should be established with a prospectively designed study that compares CRC blood test performance head-to-head with FIT performance, using colonoscopy as a reference standard, in the same patient population. Such a study should be performed head-to-head due to the variability of FIT performance from study to study internationally (5) and in the US (6,7).

Therefore, CMS should include 3 additional minimum sensitivity requirements for coverage of a blood-based CRC screening test:

Head-to-head performance comparison to FIT (due to FIT variability)
Advanced adenoma sensitivity non-inferior to FIT
Early stage cancer sensitivity non-inferior to FIT

2) CMS should use recommended tests as benchmarks to inform the covered screening interval, with guidelines as an alternative coverage pathway

Established screening intervals of guideline-recommended tests should serve as the benchmarks for interval coverage determinations. A CRC blood test with sensitivity non-inferior to FIT would therefore be anticipated to have a 1 year screening interval, one with sensitivity non-inferior to mt-sDNA should have a 3 year interval, and one with sensitivity non-inferior to colonoscopy should have a 10 year interval (8).

Although sensitivity is an important safety requirement, specificity is also critical, especially when considering interval. An annual blood-based screening test with low specificity, and hence a high false-positive rate, would ultimately send the majority of patients to colonoscopy after only a few rounds of testing, as modeled in the Peterse et al. study (9). Adoption or approval of a CRC screening test that is predicted to derive its benefit from high rates of colonoscopy referral could derail efforts to develop assays that achieve a high degree of discrimination (10). Such a modeling strategy is unlikely to work in the real-world and is little differentiated from a colonoscopy screening strategy.

To control for this, we suggest tying both specificity and sensitivity to interval. The appropriate interval would be defined by head-to-head non-inferiority with an existing recommended test for early stage cancer and advanced adenoma sensitivity and specificity as follows:

1 year interval: Sensitivity and specificity non-inferior to FIT
3 year interval: Sensitivity and specificity non-inferior to mt-sDNA
5 year interval: Sensitivity and specificity non-inferior to flexible sigmoidoscopy
10 year interval: Sensitivity equivalent to colonoscopy

Comparison with existing screening tests may not work in all cases (e.g. a 2-year interval). Therefore, major national guidelines are an appropriate alternative pathway to coverage and interval (although the minimum test sensitivity should still be met). Major guidelines are more appropriate for determining interval because the FDA does not have an interval recommendation for colonoscopy, FIT or mt-sDNA. In the absence of detailed sensitivity/specificity/interval criteria in the NCD, a major guideline recommendation should be a requirement for coverage.

3) CMS should require FDA-approval of the assay for front-line, average-risk screening

We agree with CMS that any blood-based CRC screening strategy should be deemed clinically appropriate by the FDA as a front-line option for population-level screening of all average-risk individuals. Tests that are limited by their label to a subset of the screening population (e.g. patients that have declined all other guideline-recommended screening tests) would be difficult to enforce in clinical practice, creating substantial risk for inappropriate use and attendant harms. It would also be administratively burdensome and costly to collect reliable documentation that a patient has declined all other guideline-recommended screening options prior to opting for a blood-based screening test. These challenges could ultimately hamper screening uptake.

4) CMS should cover CRC screening beginning at age 45 years, as recommended by major guidelines.

Given the growing incidence and burden of early-onset CRC, any test that fulfills CMS criteria as an appropriate front-line assay for average risk CRC screening should be initiated at 45 years of age, aligning with the recent ACS guidelines (11) and draft USPSTF recommendation statement (12).

5) CMS should clarify that follow-up colonoscopy to an initial non-invasive test is part of the screening process and a covered preventive service

Patient failure to complete the screening process poses serious public health risks. According to one study, patients who failed to follow-up on an abnormal CRC screening result had a seven-fold higher risk of dying of CRC than those who completed the follow-up process (13). And yet, approximately 3 in 10 patients with an abnormal FIT result have no documented follow-up colonoscopy within the recommended timeframe (14,15). As it stands, follow-up colonoscopies can carry significant coinsurance costs for many Medicare beneficiaries, depending on whether they are considered diagnostic. This cost obligation can discourage completion of the CRC screening process.

There is growing appreciation in the public health community about the need to address this problem. According to the American Cancer Society’s 2018 Colorectal Cancer Screening Guidelines (11), “[t]he follow-up colonoscopy should not be considered a ‘diagnostic’ colonoscopy but, rather, an integral part of the screening process, which is not complete until the colonoscopy is performed”.

A novel blood-based screening tests that requires a colonoscopy to confirm positive results could be subject to similar failures to follow-up. We therefore urge CMS to use the opportunity presented by this NCD to clarify that coverage for CRC screening using a non-invasive strategy includes both the initial screening test and any necessary follow-up colonoscopy to assess a positive result.

In closing, Exact Sciences is committed to reducing CRC burden, and believes a blood-based CRC screening strategy that meets the performance and clinical use characteristics outlined above could complement the established portfolio of effective tests in facilitating this goal. As a reflection of this commitment, Exact Sciences continues to make improvements to Cologuard (16) and advance development of a blood-based CRC screening test. Progress is being made in reducing CRC mortality (17) and increasing CRC screening rates (18). Cologuard alone has screened over 4.5 million people since 2014.

Because of the biology of colorectal cancer, it will be challenging for blood-based tests to detect early stage disease at similar rates as stool-based tests. However, choice is important and offering a blood-based test has the potential to increase screening rates, although real-world adherence to blood draw is also imperfect (19). In weighing the strength and balance of the evidence, CMS should carefully review the trade-offs between test-performance characteristics, benefits, and harms of a blood-based CRC screening test that is less accurate than stool-based screening tests before reaching a final coverage determination.

Exact Sciences thanks CMS for the opportunity to provide public comment and looks forward to working closely with the agency in the future.

Sincerely,

Durado D Brooks, MD, MPH
Deputy Chief Medical Officer
Exact Sciences References:
1. Robertson DJ, Lee JK, Boland CR, et al. Recommendations on fecal immunochemical testing to screen for colorectal neoplasia: a consensus statement by the US Multi-Society Task Force on colorectal cancer. Gastrointestinal Endoscopy. 2017;85(1):2-21.e3.
doi:10.1016/j.gie.2016.09.025 2. Ebner DW, Kisiel JB. Stool-Based Tests for Colorectal Cancer Screening: Performance Benchmarks Lead to High Expected Efficacy. Current Gastroenterology Reports. 2020;22(7). doi:10.1007/s11894-020-00770-6
3. Haug U, Knudsen AB, Lansdorp-Vogelaar I, Kuntz KM. Development of new non-invasive tests for colorectal cancer screening: The relevance of information on adenoma detection. International Journal of Cancer. 2015;136(12):2864-2874. doi:10.1002/ijc.29343
4. Meester RGS, Doubeni CA, Lansdorp-Vogelaar I, et al. Variation in adenoma detection rate and the lifetime benefits and cost of colorectal cancer screening: A microsimulation model. JAMA - Journal of the American Medical Association. 2015;313(23):2349-2358. doi:10.1001/jama.2015.6251
5. Imperiale TF, Gruber RN, Stump TE, Emmett TW, Monahan PO. Performance characteristics of fecal immunochemical tests for colorectal cancer and advanced adenomatous polyps: A systematic review and meta-analysis. Annals of Internal Medicine. 2019;170(5):319-329. doi:10.7326/M18-2390
6. Shapiro JA, Bobo JK, Church TR, et al. A Comparison of Fecal Immunochemical and High-Sensitivity Guaiac Tests for Colorectal Cancer Screening. American Journal of Gastroenterology. 2017;112(11):1728-1735. doi:10.1038/ajg.2017.285
7. Imperiale TF, Ransohoff DF, Itzkowitz SH, et al. Multitarget Stool DNA Testing for Colorectal-Cancer Screening. New England Journal of Medicine. 2014;370(14):1287-1297. doi:10.1056/nejmoa1311194
8. Bibbins-Domingo K, Grossman DC, Curry SJ, et al. Screening for colorectal cancer: US preventive services task force recommendation statement. JAMA - Journal of the American Medical Association. 2016;315(23):2564-2575. doi:10.1001/jama.2016.5989
9. Peterse EFP, Meester RGS, de Jonge L, et al. Comparing the cost-effectiveness of innovative colorectal cancer screening tests. JNCI: Journal of the National Cancer Institute. Published online August 6, 2020. doi:10.1093/jnci/djaa103
10. Ransohoff DF. Evaluating a new cancer screening blood test: Unintended consequences and the need for clarity in policy-making. JNCI: Journal of the National Cancer Institute. Published online August 6, 2020. doi:10.1093/jnci/djaa104
11. Wolf AMD, Fontham ETH, Church TR, et al. Colorectal cancer screening for average-risk adults: 2018 guideline update from the American Cancer Society. CA: A Cancer Journal for Clinicians. 2018;68(4):250-281. doi:10.3322/caac.21457
12. U.S. Preventive Services Task Force. Draft Recommendation Statement- Colorectal Cancer: Screening. https://www.uspreventiveservicestaskforce.org/uspstf/draft-r…
13. Doubeni CA, Fedewa SA, Levin TR, et al. Modifiable Failures in the Colorectal Cancer Screening Process and Their Association With Risk of Death. Gastroenterology. 2019;156(1):63-74.e6. doi:10.1053/j.gastro.2018.09.040
14. Chubak J, Garcia MP, Burnett-Hartman AN, et al. Time to colonoscopy after positive fecal blood test in four U.S. health care systems. Cancer Epidemiology Biomarkers and Prevention. 2016;25(2):344-350. doi:10.1158/1055-9965.EPI-15-0470
15. McCarthy AM, Kim JJ, Beaber EF, et al. Follow-Up of Abnormal Breast and Colorectal Cancer Screening by Race/Ethnicity. American Journal of Preventive Medicine. 2016;51(4):507-512. doi:10.1016/j.amepre.2016.03.017
16. Domanico M, Kisiel J, Gagrat Z, et al. ACG 2019 Annual Scientific Meeting2019 | eventScribe Itinerary Planner. Accessed November 9, 2020. https://www.eventscribe.com/2019/ACG-Abstracts/Presinfo/Pres…
17. National Cancer Institute, Surveillance E and ERP. Cancer Stat Facts: Colorectal Cancer. Published 2020. Accessed November 9, 2020. https://seer.cancer.gov/statfacts/html/colorect.html
18. Centers for Disease Control and Prevention. Use of Colorectal Cancer Screening Tests (2018 Behavioral Risk Factor Surveillance System) | CDC. Published October 22, 2019. Accessed November 9, 2020. https://www.cdc.gov/cancer/colorectal/statistics/use-screeni…
19. Moffet HH, Parker MM, Sarkar U, et al. Adherence to laboratory test requests by patients with diabetes: The diabetes study of Northern California (DISTANCE). American Journal of Managed Care. 2011;17(5):339-344. Accessed November 9, 2020. /pmc/articles/PMC3189790/?report=abstract

https://www.cms.gov/medicare-coverage-database/details/nca-v…

[Gekko279]

Zum 30. September 2020 verfügte das Unternehmen über liquide Mittel von EUR 6,6 Mio. (inkl. marktgängiger Wertpapiere)

wegen Kurzarbeit dürften wohl noch mehr als 5 Mio. in der Kasse sein. das dürfte wohl bis zur endgültigen Entscheidung reichen. danach kann abgewickelt werden. es sei denn er findet neue Investoren, die ihn weiter durchfüttern. danach sieht es aber bislang nicht aus.

[Gekko279]

Antwort auf Beitrag Nr.: 65.702.565 von dogweiler am 13.11.20 18:40:32

da ist deine Brückenfinanzierung, die mit GH vergleichbar ist

https://www.ndr.de/nachrichten/niedersachsen/Gifhorn-Ist-Bru…

[dogweiler]

Antwort auf Beitrag Nr.: 65.702.418 von Gekko279 am 13.11.20 18:29:14

Nun sollten wir um die Brücke diskutieren, die GH hier wohin bauen will.

[Gekko279]

Antwort auf Beitrag Nr.: 65.701.809 von dogweiler am 13.11.20 17:43:03

1. war es ein Vergleich
2. hätte es nach offizieller Lesart noch teurer werden können.
3. es war ein Kompromiss

über den Nutzen kann man streiten, bei weiterer Zeitverschiebung hätte es aber teurer werden können. und nun?!