MolDX Creates Guidelines for Circulating Tumor DNA Validity Studies (Liquid Biopsy)

When will payers have explicit policies covering liquid biopsy...soon?   Possibly, since Medicare's MolDX policy group has issued analytical validity guidelines for circulating DNA somatic tumor mutations.   There wouldn't be much reason to have these test assessment guidelines - which look like a lot of effort and detail - unless there was some foreseeable point when the tests would be covered.

The guidelines 8 pages long and were originally issued May 20, 2016.

The UPDATED V2 was posted by MolDx four days later, on May 24, and is here.

The guidelines open by stating three cardinal requirements:

General Laboratory Requirements 

A. CLIA certification; and
B. New York State Department of Health (NYSDOH) final test approval; and
C. Participation in an external proficiency testing (PT) program for ctDNA-based somatic variant detection that addresses all reported variant types, when available. Any variant types for which external PT is not available should be assessed by alternative PT, as required by CLIA. 

It looks like these guidelines are written now in preparation for a future state of affairs, when NYS develops liquid biopsy guidelines (someday?) and when CAP or other directly ctDNA-based standards are available.

A redline of V2 versus the four days older V1, is in the cloud, here.

The guidelines are built around four classes of abnormalities (point mutations, small indels, large indels, and rearrangements).  Generally results should be verified by orthogonal technologies.  "Contrived" samples are allowed, e.g. cell lines, where appropriate or necessary.

The FDA will hold a workshop on liquid biopsy tumor panels on July 19 (here).   I continue to recommend people read the thorough study by Sacher et al., here, which however looked only at point mutations by ddPCR.