- On September 15, 2016, MolDX posted a revised LCD for lung cancer gene panels, with broader patient coverage but requiring a more burdensome registry.
- By September 29, 2016, the revised draft LCD for public comment was taken down (became a dead link).
- The MolDX LCD for lung cancer was instead editorially updated as "L36143 Revision 5" which includes broader coverage and "clarifies" (quote) the registry requirements.
- The new LCD as "Revision 5" is online at CMS here, with a cloud archive of the September 29 revision, here.
- In their November 5, 2016, investor call, Foundation Medicine said that their lung cancer gene panel test was being run from their (new) North Carolina lab and covered under this LCD. Here.
Because the LCD change expands coverage (to a larger population of lung cancer patients), MolDX may have determined it could be posted as an editorial coverage expansion rather than as a new draft LCD version requiring public comment.
Original September blog continues:
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On Thursday, September 15, 2016, MOLDX posted a revised LCD for broad gene panel testing in lung cancer.
A longer list of registry requirements has been written into the revised LCD. However, coverage has been significantly expanded. The LCD allows first line use of genomic panels for testing and is no longer predicated on only light or non smoking lung cancer patients.
A redline comparison of the existing Noridian LCD and the new proposed LCD is in the cloud, here.
The registry requirements are considerably longer and more detailed, as shown in the comparison table below.
OLD REGISTRY
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NEW REGISTRY
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o Patient demographics including patient age when the specimen was collected, and gender;
o Sample information including whether CGP testing was performed on the same specimen DNA as the original test result, a re-biopsy from the same tumor site, or a re-biopsy from a different tumor site, and the dates of biopsy for the original non-CGP and CGP tests;
o Non-CGP test methodology resulting in a negative EGFR mutations, or ALK or ROS1 rearrangements;
o Alterations in the following genes: ALK, BRAF, EGFR, HER2, KRAS, MET, ROS1, and RET.
o Any treatment received after CGP testing, the current response status and duration of response
· Reports will be delivered every 6 months in a mutually acceptable format.
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· Collect CGP test and patient specific information in the MolDX approved registry that meets the following characteristics:
o National in scope and open to any lab, (commercial or academic), and any provider location (academic, community);
o Independent of the participating laboratory (commercial or academic);
o Governed by a well-designed protocol listed on clinicaltrials.gov with national cross-institution leadership, patient consent, Institutional Review Board (IRB) approval, end points, and regular reporting;
o Requires and verifies that CGP testing is essentially equivalent to MolDX Analytical Performance Specifications for Comprehensive Genomic Profiling AND has demonstrable plans to maintain compliance to both MolDX and other published standards;
o Will collect detailed genomic information as detailed by the registy– including raw (FASTQ or BAM) data and variant call data in connection with clinical outcomes and report these to the registry in a timely fashion;
o Will compare CGP identified mutations in the EGFR, ROS1 and ALK regions to companion diagnostic tools (where exist) on a subset of patients to determine concordance;
o Organization overseeing the registry or essential partners to that organization cannot have a history of data siloing (e.g. not sharing data with competitors) or history of requiring physician-groups purchase or lease any propriety software;
o Registry organization has to have shown a strong commitment and effort to work with national organizations committed to data sharing (i.e. Genetics Data Commons, NCI, Vice President Biden’s Moonshot initiative, etc.);
o Registry will allow open, non-commercial research access to the database (with appropriate curation), and will allow equal access to commercial groups;
o Non-profit registry organization is preferred;
· Registry to report to Palmetto GBA every six months the following:
o Number of patients enrolled in registry
o Biomarker prevalence in registry patients
o Treatments and time to progression in patients with a given biomarker per line of therapy for at least 2-3 lines of therapy
o Overall survival of patients by biomarker status and treatment profile
o Concordance analysis of biomarker testing results between CGP and a FDA approved companion diagnostic test (where one exists for a given biomarker)
· Registry will assure publication of test results and clinical findings on a regular basis
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The body of the new proposed LCD follows:
Comprehensive Genomic Profiling (CGP) Test Description:
CGP analysis is defined as a single test using tumor tissue only (i.e., not matched tumor and normal) that does not distinguish between somatic and germline alterations and can detect the following classes of alterations:
- Base pair substitutions (including single nucleotide variants (SNVs))
- Insertions and deletions (Indels; up to 70 bp)
- Copy number variations (CNVs; including both amplifications (ploidy < 4 with copy number = 8) and homozygous deletions (ploidy < 4 with copy number = 0)
- Translocations
Other non-NGS testing platforms may be considered if they can similarly detect all four classes of alterations with comparable test performance as CGP.
MolDX CGP Analysis Coverage
CGP analysis is covered only when the following conditions are met:
- Patient has been diagnosed with advanced (Stage IIIB or IV) NSCLC; and
- Patient has not been tested for genomic alterations OR previously tested negative for EGFR mutations, ALK rearrangements, or ROS1 rearrangements through non-CGP methods; and
- Testing is performed by a lab that satisfies Palmetto GBA’s Analytical Performance Specifications for Comprehensive Genomic Profiling (M00118, v1).
Palmetto GBA expects participating laboratories to:
- Demonstrate compliance with Palmetto GBA’s Analytical Performance Specifications for Comprehensive Genomic Profiling criteria (M00100, v1) in one of two ways:
- Submit AV validation data directly to Palmetto GBA, or
- Submit AV validation data to Palmetto GBA approved registry that will report compliance to Palmetto GBA.
- Collect CGP test and patient specific information in the MolDX approved registry that meets the following characteristics:
- National in scope and open to any lab, (commercial or academic), and any provider location (academic, community);
- Independent of the participating laboratory (commercial or academic);
- Governed by a well-designed protocol listed on clinicaltrials.gov with national cross-institution leadership, patient consent, Institutional Review Board (IRB) approval, end points, and regular reporting;
- Requires and verifies that CGP testing is essentially equivalent to MolDX Analytical Performance Specifications for Comprehensive Genomic Profiling AND has demonstrable plans to maintain compliance to both MolDX and other published standards;
- Will collect detailed genomic information as detailed by the registy– including raw (FASTQ or BAM) data and variant call data in connection with clinical outcomes and report these to the registry in a timely fashion;
- Will compare CGP identified mutations in the EGFR, ROS1 and ALK regions to companion diagnostic tools (where exist) on a subset of patients to determine concordance;
- Organization overseeing the registry or essential partners to that organization cannot have a history of data siloing (e.g. not sharing data with competitors) or history of requiring physician-groups purchase or lease any propriety software;
- Registry organization has to have shown a strong commitment and effort to work with national organizations committed to data sharing (i.e. Genetics Data Commons, NCI, Vice President Biden’s Moonshot initiative, etc.);
- Registry will allow open, non-commercial research access to the database (with appropriate curation), and will allow equal access to commercial groups;
- Non-profit registry organization is preferred;
- Registry to report to Palmetto GBA every six months the following:
- Number of patients enrolled in registry
- Biomarker prevalence in registry patients
- Treatments and time to progression in patients with a given biomarker per line of therapy for at least 2-3 lines of therapy
- Overall survival of patients by biomarker status and treatment profile
- Concordance analysis of biomarker testing results between CGP and a FDA approved companion diagnostic test (where one exists for a given biomarker)
- Registry will assure publication of test results and clinical findings on a regular basis
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CED in LCDs
The use of CED is being developed by MACs, especially by MOLDX, as case law in the making, so to speak.
CMS National Coverage Determinations cover "Coverage with Evidence Development" under Section 1142 of the Social Security Act, which allows payment for research studies under the Agency for Healthcare Research and Quality. Essentially, CMS is allowed to cover healthcare services that are reasonable and necessary to treat disease, OR, that are reasonable and necessary to carry out the purposes of Section 1142. This is explained in a 2014 guidance published online by CMS (here).
Documents like the lung cancer genomic coverage policy shown above are LCDs, which are defined in statute as policies about what is, or is not, reasonable and necessary (aka 1862a1A)on a contractor-wide (MAC-wide)basis. CMS states that "the definition of LCD in the Social Security Act does not support use of CED under 1861(a)(1)(E) {the section that unites CMS payment with AHRQ studies}." CMS adds, "MACs may use LCDs to determine coverage of items and services to they extent they do not conflict with national Medicare policy."
If we use the framework that LCDs pay for things that are reasonable and necessary, and never pay for things that are not reasonable and necessary, we would come to the conclusion that the lung cancer gene panels are reasonable and necessary for healthcare if they inform both healthcare and a later registry (including outcomes well into the future from the paid service).
Since the LCD adds that the gene panel is paid only if in the registry, and not outside it, it implies that the gene panel service would be an event that is not reasonable and necessary for the cancer patient's healthcare sans the registry aspect. Some other MACs (e.g. NGS and Cahaba) cover NGS gene panels in lung cancer sans the registry, so there is currently some observed variance in opinion among MACs as whether a registry is necessary.
MolDX terms its registries "Coverage with Data Development" or CDD; this makes sense since the online CMS document says that "Statute...does not support use of CED...in LCDs."
A recent LCD on the Veracyte PERCEPTA test also includes a registry (here), as do several MolDX LCDs for prostate cancer gene panel tests (Decipher, Myriad Prolaris, Oncotype DX Prostate, Metamark).
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MED-C REGISTRY
MOLDX launched its LCD for lung cancer gene panel testing with requirements that cases be entered in a Registry. The preferred Registry is called “MED-C” which is managed by oncologist Dr. Dane Dickson. Before 2015, Dr. Dickson was a part-time extramural consultant to MolDX.
The MED-C website is here: https://med-c.org/
Press release on its advisory board is here: http://www.24-7pressrelease.com/press-release/medc-announces-stellar-investigator-core-for-ngs-registry-427727.php
Press release that it has IRB approval is here: http://www.24-7pressrelease.com/press-release/medcs-groundbreaking-ngs-registry-gets-irb-approval-428060.php
