Friday, August 31, 2018

MolDx Releases Set of New LCDs

A Genomeweb article on August 30, 2018, notes that MolDx has released a draft LCD favorable to the Veracyte test Envisia, for pulmonary fibrosis (here).

Four other draft LCDs were also released on the WPS MAC website.  MolDx LCDs may appear first at any MolDx-participating MAC, depending on the various MACs' calendars.

A search of new LCDs this week is available via the CMS LCD database (here).  I've put a bundle of five new MolDx LCDs in the cloud here.

ClonoSEQ (MRD)
In DL37917, coverage is proposed for the ClonoSEQ Assay for minimal residual disease (MRD) in certain lymphoid malignancies.  Analytical validity is cited to "data on file" at Adaptive that is "designed to meet FDA standards" (LCD fn 15).  Guidelines and several validity studies are cited.  MolDx summarizes that "studies have demonstrated the accuracy and clinical utility of clonoSEQ in predicting clinical outcomes in a variety of myeloma settings and timepoints."  Validity in acute lymphoblastic leukemia (ALL) is discussed separately.    While separate coverage is described for myeloma and ALL, criteria are factors such as use in transplant decision-making, as a test for drug therapy response, and testing for sustained MRD "per guidelines at time" as indicated in various guidelines for hematopoeitic MRD.

Veracyte Envisa (Lung disease)
In DL37919, the Veracyte Envisia test will be covered for diagnosing interstitial lung disease in patients who lack a definitive CT pattern and where a bronchoscopic biopsy may be used instead of a surgical lung biopsy.   MolDx notes it consulted specialists from Mayo, Columbia, and USC in addition to its own review.  Criteria for coverage including high resolution CT (hrCT, defined as 1mm reconstructions) which are not definitive.

Invivata InvisionFirst (Liquid Biopsy)
Inivata is a lab dedicated to liquid biopsy testing in oncology.  In DL37921, its LBx test ("InvisionFirst") is covered at diagnosis or at progression in lung cancers that are advanced stage and meet criteria for missing genomic information.   Earlier this year, MolDx covered the Guardant G360 test under similar conditions.

 MyPath Melanoma (Ambiguous Cases)
In DL37923, the MyPath melanoma assay from Myriad is covered for "diagnosis or exclusion of melanoma" in a biopsy when ordered by a board certified dermatologist; the cutaneous neoplasm is ambiguous by histology alone; and the uncertainty impacts the patient such as risk of re-excision and sentinel node biopsy.   According to the LCD, two validation studies assessed concordance compared to histopathological experts.  (This is obviously good, but doesn't directly address the accuracy in cases where histopathology has no diagnosis and experts disagree.)  A third study looked at outcomes at a median of 6 years in 182 prior biopsies.

Decipher Prostate Prognostic
In DL37911, the Decipher prostate prognostic test is covered in low-risk prostate cancer as defined by NCCN.   MolDx has generally granted earlier coverage for prostate risk tests in low risk disease, where the test is most likely to verify a low-risk, lower intervention stance is justified (as opposed to deselecting therapy in higher risk cases).   I suspect this must be a new LCD only for the WPS MAC and has existed in other MolDx MACs.

Several of these assays are NGS assays in cancer, so the LCD should be in compliance with the recent CMS NGS NCD for uses of NGS in cancer.  For example, the Envisia LBx test LCD states, "May be used once per lifetime," following the once-per-patient requirement in the NCD.

Statements of "Promising Data"

Some LCDs include concluding evaluations that data is "promising" and that ongoing coverage is dependent on forthcoming publications.  For example, in DL37919, we read:

"The clinical utility of the Envisia genomic classifier to aid in the diagnosis of patients with an ILD of unknown cause and suspected of IPF, as defined in the intended use above, is quite promising. This contractor believes that forthcoming clinical studies in these patients will demonstrate improved patient clinical outcomes. Continued coverage for Envisia testing is dependent on annual review by this contractor of such data and publications."

This isn't universal, e.g. the MyPath Melanoma LCD  and Inivata LCD don't have this concluding test, and the other three do have it, even though the MolDx evidence ratings shown for ClonoSeq are a bit higher than for MyPath.

I'm not sure how precisely MolDx, or its differently reviewers, classify evidence by "quality, strength, and weight" (see my blog on these MolDx terms here).   With that warning, below is a table with the ratings for the five LCDs discussed today.

Note that the  last row, "Total Citations," is not the citations of the product, but the total citations used throughout the LCD discussion. 

click to enlarge