Thursday, July 9, 2020

Flurry of Reviews: Pharmacogenetics, Liquid Biopsy, TMB, Infectious Disease Dx Stewardship

The last week has brought a landslide of interesting review articles on fast-changing topics.  I'll highlight several below.

Overview:  Economics of Molecular Testing from AMP

Let's start with a 19-page review in the new J Molec Dx by Sireci et al, entitled:  "Molecular Pathology Economics 101: An Overview of Molecular Diagnostics Coding, Coverage and Reimbursement."  See the main article here, and a one-page supportive Op Ed, by Zehnbauer, here.

Pharmacogenomics and Clinical Utility - 3 Articles, One Conference

Article #1
The Pharmacogenomics Action and Reimbursement Coalition (PARC) has produced a 12-page review article in the journal Pharmacogenomics on the state of play for PGx, clinical utility, and reimbursement.  

They provide a thorough review that includes, but is not limited to, the activities of CPIC (the Clinical Pharmacogenetics Implementation Consortium), which has published 21 guidelines spanning 46 drugs and 19 genes.  CPIC is especially important because it is officially recognized as authoritative for Medicare coverage under a new MolDx LCD (here).

Find Eichmeyer et al. here (subscription).

Article #2
But wait, there's more.  PARC also supported the production of "PARC report: Health outcomes and value of personalized medicne interventions," also in Pharmacogenomics, Mitropoulou et al.  Article here.  Also subscription.

Article #3
But wait, there's a third.  PARC also supported "PARC report: a health-systems focus on reimbursement and patient access to pharmacogenomics testing," also in Pharmacogenomics, Rogers et al.  Article here.  Subscription.

...AND...Conference October 8
Finally, PARC supports the "Pharmacogenomics Access and Reimburesment Symposium," Virtual, October 8, 2020 (registration $199-400).  Find it here.

Liquid Biopsy - Payor Review; CRC Review

UCSF's Transpers institute studies the translational medicine processs around precision medicine, including payor behavior.  Douglas et al. have a brand-new publication on private payer, and Medicare, coverage of circulating tumor DNA testing (e.g. liquid biopsy for tumor oncogenes).   They are willing to dive into the details - for example, they note that MolDx brought out an LCD last year for the Guardant test alone, but finalized it as a potential "umbrella" policy including other tests "with similar performance."  (They don't note that Noridian declined to finalize that LCD, a puzzle for MolDx watchers (here).)

See Douglas, Gray, & Philips here.  See trade journal coverage of their findings at Genomeweb here.  This same group published an excellent review of the lab benefit manager (LBM) industry last fall in Health Affairs (here; see also Cahan at STAT, here).

At Nature Reviews Clinical Oncology, see an open access new review of ctDNA applications in colorectal cancer (Dasari et al., here).  This one spans the clinical utility spectrum, from screening tests, to minimal residual disease detection after surgery, to "regular" liquid biopsy for tumor oncogenes.

See also a white paper supported by PMC, Illumina, BCBSA, Concert Genetics, on complexity of payer policy and erratic utilization of genomics.  Here.

TMB and Controversy

A few months ago, Friends of Cancer Research published its Phase I review on harmonization of tumor mutational burden (TMB); see Merino et al, here.  And see trade press from April here.  

But there's more.  In June, FDA approves Keytruda with the FMI CDx test newly reporting TMB (with a 10% cut off) as an FDA-endorsed companion diagnostic (here).   Previously, Keytruda was approved for high-MSI tumors, which are quite uncommon (and there's no FDA-approved MSI test, either, although Promega and Biocartis are trying to achieve FDA endorsement, here).   

"Ignited Controversy."  See an article at Precision Oncology News that the Keytruda/FMI/TMB approval has "ignited controversy" among TMB experts - here.  In part, there's still debate about the least burdensome cutoff acceptable to the FDA (10 mutations per Mb) and a higher cutoff that would select patients with bigger clinical response (perhaps 30 - see article).   

Infectious Disease - COVID Review, Diagnostic Stewardship

The new listings for in-press articles at J Molec Diagnostics include:
  • A review article by Nolte et al. on molecular testing for COVID - here.   Focuses on the policy and operations perspective as seen by molecular lab directors in the grip of major social, regulatory, and supply chain forces.
  • Similarly, AMP, ASM, CAP, others ask White House to address testing supply shortages on July 8; here.   Genomeweb here.
  • A review article on diagnostic stewardship in the field of infectious disease, focused on new rapid molecular test methods - by Morjaria & Chapin - here.  Their essay is informal and built around a case study; for a deeper dive they refer readers to Messacar et al. 2017 - here.