Friday, February 24, 2017


This blog carried an article about expanded carrier screening on February 20 (here).  Unknown to me at that time, this week American College of Obstetrics and Gynecology has issued two new guidance documents on carrier screening, #690 here and #691 here.

ACOG split its discussions into two papers, the first, "Carrier Screening in the Age of Genomic Medicine" (#690) and the second, "Carrier Screening for Genetic Conditions" (#691) which includes sections for Ashkenazi and for panethnic screening.

Medpage covers the new guidance documents here (February 23, 2017).

In my February 20 blog, I noted that the public agenda for a recent AMA CPT meeting included a code proposal for expanded (panethnic) carrier screening.   I also noted that the somewhat dated, decade old available guidance documents were unusual from a health technology assessment or evidence based medicine perspective.  However, that blog is now largely superseded by the new ACOG positions.

For some recent links in the field:

  • Medpage Today (February 23, 2017) ACOG new guidance - here.
  • Huffington Post (February 20, 2017 - not tied to ACOG) - Consumer update - here.
  • Genomeweb (December 5, 2016)- Roche to offer GoodStart Genetics testing - here.
  • Genomeweb (November 2, 2016) - Good Start Genetics and Amazon - here.
  • OBGYN Trade journal (June 16, 2016) - Are you prepared for ECS? - here.
  • JAMA (August, 2016) - Haque et al. study of over 300,000 cases - here.
  • Molec Genet Genom Med (2016) NGS carrier screening cost effectiveness - here.

Tuesday, February 21, 2017

Brief Blog: Tapestry Networks and the Diagnostic Quality Assurance Pilot for CDx

At the 3000-person, 25th annual "Molecular Med TriCon" in San Francisco this week, multiple mentions of the Tapestry Networks "Diagnostic Quality Assurance Pilot."

Here are two entry points.  First, on November 18, 2016, the FDA announced it was dropping for now its plans to regulate LDT diagnostics through guidance.  Second, on February 1, 2017, a consortium of important organizations including the American Cancer Society and the American Society for Clinical Oncology wrote Senate leadership that something must be do to assure LDT laboratory quality (here).

So there's some tension out there - what will happen next?

Along the way, there is the "Quality Assurance Program for Companion Diagnostics," a multi stakeholder effort (leadership ranging from Abbott to Emery) to establish processes "by which all key stakeholders can be satisfactorily assured of molecular test equivalence across laboratories."   Within the multi-purpose Tapestry organization, this is led by a Working Group called, "SPOT/Dx" - "Sustainable Predictive Oncology Therapeutics and Diagnostics."   SPOT/Dx was launched by Tapestry in 2013.

For more information on the QAP-CDx, see these resources:
  • Project homepage at Tapestry Networks, here.
  • 15-page presentation by Barbara Zehnbauer, Emery, at AMP November 2016 (here).
  • 3-page article by Zehnbauer et al. in Journal of Molecular Diagnostics, January 2017 (open access, here.).
  • At the Tapestry website, a 4-page Q&A dated February 2017, here.
More after the break.

Monday, February 20, 2017

AMA Endorses Expanded Carrier Screening Through Online CME Course


This blog was written on February 20, 2017, and was based on AMA CME for expanded carrier screening and the fact that a new code for this service appeared on the AMA CPT agenda recently.  

Much of the further discussion, deeper below, is superseded by new ACOG documents released February 22, 2017.  

I leave the original blog below, but see the newer version, February 24, 2017, here.


Original February 20, 2017 blog:

The American Medical Association has a dedicated website for precision medicine issues and resources, here.    

The AMA precision medicine center includes up-to-date CME modules for Expanded Carrier Screening, prenatal cell-free DNA screening, somatic cancer panel testing, and other topics in clinical genomics.

According to an AMA and Scripps joint press release, the first module released in this CME series was Expanded Carrier Screening (press release here).

The Expanded Carrier Screening CME is here, at AMA, and it is also crosslisted as a CME course on the American College of Obstetrics and Gynecology website, here.

Expanded Carrier Screening In Perspective

This CME is timely, because according to the agenda for the February 2017 AMA CPT meeting, a code for Expanded Carrier Screening was under consideration (also called Panethnic carrier screening).

Usage of this clinical service is estimated to be higher than 200,000 cases per year.   An August 2016 publication in JAMA reported the results of testing in over 300,000 individuals of diverse racial and ethnic backgrounds (Haque et al., here.)

AMA CPT created a code for Ashkenazi Carrier Testing effective January 1, 2016.   However, looking into available guidance documents, the introduction of screening codes for germline genetic panel tests seem to raise unusually complex issues in terms of guideline generation and clinical utility assessment - more after the break.


MolDX's Dr. Gary Spitzer Speaking on Liquid Biopsy Evidence: June 2017, SF

This June, the Second Annual Liquid Biopsy Summit will be held in San Francisco, June 21-23 (website here).    The conference includes 3 short courses, panels, and some 25 presentations.

Dr. Spitzer's Presentation

Dr. Gary Spitzer, the MolDX Director for Clinical Validity and Clinical Utility Evaluation, will be chairing the morning session on Friday, June 23.   In addition, Dr. Spitzer's own presentation will focus on "Clinical Utility Needs of ctDNA Assays versus Research Utility."   Dr. Spitzer's presentation will focus on (a) the optimal use of transparent prospective registries and (b) ways that effective data can be gathered at lower costs.

Dr. Spitzer's Background

Dr. Spitzer has held a series of prominent national roles in oncology, including Deputy Director of the Bone Marrow Transplantion Program at M.D. Anderson, and clinical leadership roles at St. Louis University, Georgetown, and Bon Secours.   He has been a senior clinical consultant to the MolDX program for almost two years, since March 2015.  His LinkedIn webpage is here.

Rapid Advances in Liquid Biopsy

A lot has occurred between the First and Second Annual Liquid Biopsy Summits, with numerous policy advances in the field of Liquid Biopsy.  For example:

  • The FDA approved the Roche Cobas EGFR liquid biopsy test for several mutation sites (see JAMA, here).  
  • The FDA also held a joint all-day conference in Washington with AACR on liquid biopsy last July (here).   
  • NCCN guidelines recommend "If repeat biopsy [in lung cancer] is not feasible, plasma biopsy should be considered."  
  • ASCO's Year-in-Review for CY2016 featured two pages on the emerging clinical importance of advances in liquid biopsy (here).  
  • In the 21st Century Cures Act, Congress allocated $2B for new innovative cancer research, a substantial portion of which will go to public-private efforts in liquid biopsy.  
  • The dedicated liquid biopsy startup Grail announces plans to raise $1B while bringing on board the FDA's leader for precision medicine, Dr. Liz Mansfield.  

The MolDX program has provided technical standards for the approval of liquid biopsy tests for coverage, here.

Brief Blog: Links to Rough Transcripts of Both Price Confirmation Hearings

CSPAN provides onlive video archives of both of Secretary Tom Price's hearings for head of Health & Human Services - January 18 at the HELP committee and January 24 at the SFC, here and here, respectively.

CPAN also provides raw block capital closed captioning text.

I have simply collated the raw real time closed captioning text into one long Word document - page 1-52 for the HELP hearing and 53-157 for the SFC hearing.

It's not pretty but can be read/skimmed better than the 7 hours of video.

  • In the cloud, here.   

Friday, February 17, 2017

Brief Blog: Unique Annotated Transcript of Seema Verma Senate Hearing Here

On February 16, 2017, President Trump's candidate for administrator of CMS was in a 2 1/2 hour hearing at the Senate Finance Committee.

Get an unofficial 59 page cloud transcript of the full hearing Q&A - here.

For additional links and citations to news articles, see our earlier blog, here.

Brief Blog: CMS Candidate Seema Verma Testifies at Senate Finance Committee

On February 16, 2017, CMS leadership candidate Seema Verma testified in a nearly three-hour session of the Senate Finance Committee.
  • C-Span archives the entire video here. [*]
  • For a cloud 59-page unoffical transcript of the hearing, annotated and provided by this blog, here.    

  • The Administration's "Transition 2017" Youtube channel has a few brief sound bites online, here.

  • Early coverage at Modern Healthcare, here; at Reuters, here.
  • Opening Statements (Senate Webpage here.)
    • Senate Hatch: here.   Senator Wyden: here.  Verma: here.
    • All together in one PDF (13pp): here.
  • Later coverage at Fox Opinion (here), Becker's (here), CNN (here), and Atlantic (here).

My original November 2016 collation of articles on Verma, including some updates, is here.

More after the break.

Brief Blog: Narrow Networks in Laboratory Medicine

For several years, Dark Report and other trade journals have discussed the rising role of narrow-network payers and the impact on the lab industry, which often has little control over which payers support the patients whose samples arrive at the lab.

Dark Daily, the open access blog associated with Dark Report, runs an article on narrow networks today, with citations to a study by McKinsey and company.

  • Dark Daily Blog here.
  • McKinsey webpage here and PDF version of the data here.

For a 2014 article at Dark Daily on the same topic, here.  For a 2015 open access article at Health Affairs, not specific to the lab industry, here.

Thanks to Katherine Tynan for highlighting.  This weekend, February 19, several colleagues and I will have the opportunity to teach a short course chaired by Tynan on lab regulatory and reimbursement trends at the Molecular Med TriCon conference in San Francisco. 

Tuesday, February 14, 2017

Brief Blog; CMS Candidate Seema Verma; Senate Confirmation Hearings Will Be Feb. 16

President Trump's candidate for head of CMS, Seema Verma, is scheduled to interview with the Senate Finance Committee on Thursday, February 16.  Story at National Law Review (open access, here).

Verma is nationally known for her consultancy that helps states develop, implement, and manage Medicaid reforms (here).

Brief Blog: Evidence Street and MolDX

In a publicly available deck from December 2016, Dr. Louis Jacques, Chief Clinical Officer at the consultancy ADVI, predicted that in 2017 the BCBS Evidence Street program and the CMS MolDX program would "develop a common portal for lab test dossier submission and review."  (Here, p. 4.)

In a subscription deep dive article at Genomeweb, journalist Turna Ray updates on the Evidence Street program through interviews with BCBS, Dr. Jacques, and other stakeholders.   For the subscription article, here.

BCBSA Evidence Street displaced the prior BCBSA TEC website, which had been largely open access, with a subscription model.   The Evidence Street website is here.  Favorable reviews are available to companies and can be brought to the public's attention through press releases (e.g., here and here.)   BCBSA itself is careful to position the reviews as evidence reviews, not endorsement of the test relative to any particular higher or lower bar for a coverage decision.

Tuesday, February 7, 2017

Brief Blog: 21st Century Cures and the CMTP Focus on Real-World Evidence

Real world evidence has been extensively discussed in recent years, two Washington highpoints being a June 2016 white paper on RWE by the Bipartisan Policy Center (here) and 21st Century Cures, Section 3022, encouraging the FDA to look deeper into RWE in approval decisions (here, here).

(The FDA weighed in on its view of RWE in the New England Journal, December 8, 2016, here.)

The Green Park Collaborative, organized by the Baltimore-based Center for Medical Technology Policy (CMTP), has set up a resource webpage with multiple detailed documents to help parties assess and validate the quality of Real World Evidence.

Website here.  39-page white paper on the RWE Decoder project, here.

For a video on the evidence framework goals of CMTP, see an interview with its leader Dr. Sean Tunis, here.

For a February 21, 2017 editorial in JAMA on observational evidence, see here.

The FDA"s Regulation for Expanded Carrier Screening

Last summer, there was a publication in JAMA by Haque et al., the largest study ever undertaken of recessive carrier genes distributed over a population of over 300,000 individuals (here).

After a well-known intervention at 23andMe, the FDA released self-implementing regulations for autosomal recessive test systems.  The regulations are unusual and innovative, dependent in large part on the laboratory's webposting of accuracy and validity data.

Most FDA product category regulations (21 CFR 800ff.) are only a few words long, at most a couple sentences.  For example, Agendia Mammaprint and Nanostring Prosigna breast cancer prognostic tests are cleared under 866.6040:
A gene expression profiling test system for breast cancer prognosis is a device that measures the ribonucleic acid (RNA) expression level of multiple genes and combines this information to yield a signature (pattern or classifier or index) to aid in prognosis of previously diagnosed breast cancer.
In contrast to that type of product classification, the regulation for expanded carrier screening is 3000 words long and runs six pages when clipped into a single-spaced word document.

The regulation (866.5940) is copied below, after the break.   The original Federal Register publication (80 FR 65626ff, October 27, 2015) is here.

The regulation requires hyperlinked reference to credible sources of validity information "such as GeneReviews" that is not otherwise reviewed by FDA before presentation to physician and patient.  This is similar to new guidance on biopharma communications with payers on economic evidence, which must be based on "competent and reliable scientific evidence" (CARSE) not otherwise reviewed by FDA (here).

Brief Blog: PMC Publishes Two Open Access Papers on Access to Personalized Medicine

The Personalized Medicine Coalition has published an open-access white paper and an open access journal article on the integration of precision medicine in healthcare.

The five-page white paper is online at PMC, here.  See the contributors list for a who's-who of thought leaders.

The 12-page academic article, by Pritchard et al, is online at the journal Personalized Medicine (14:141-152), here.

See similarly, a six-page new article in Journal of Precision Medicine by Subha Madhavan, "Barriers to Implementation of Precision Medicine in the US Health System," here.

Abstract of Pritchard et al., after the break.

Monday, February 6, 2017

Survey Finds 72% Favor Gottlieb for FDA Chief

Biopharma companies do not pick the next head of FDA - the President nominates and Congress confirms.

That said, columnist John Carroll reports a survey in which 72% of biopharma executives favored Dr. Scott Gottlieb as head of FDA.   Other candidates discussed in recent media tracked far behind - Jim O'Neill at 8%, Joseph Gulfo at 9%, and Balivas Srinivasan at 2%.

See Carroll's article, here.

Sunday, February 5, 2017

Digital Genomics: DarwinHealth as an Oncology Case Study

In early 2016, I gave a talk for the first time on Digital Genomics, creating a short white paper as a leave-behind for attendees (here; see also here).  This coming summer, I have the opportunity to chair a panel on Digital Genomics at the 1000-person NextGenerationDX conference in Washington August 15-18 (here).

The new issue of Nature Reviews Cancer contains a fascinating deep-dive article on the concept lof clinical digital genomics by authors at Columbia University and DarwinHealth, a New York-based genomics startup.

More after the break.