Foundation Medicine Draft NCD (Operational Text)

https://www.cms.gov/medicare-coverage-database/details/nca-proposed-decision-memo.aspx?NCAId=290&bc=ACAAAAAACAAAAA%3d%3d& 

A. General

Clinical laboratory diagnostic tests can include tests that, for example, predict the risk associated with one or more genetic variations. In addition, in vitro companion diagnostic laboratory tests provide a report of test results of genetic variations and are essential for the safe and effective use of a corresponding therapeutic product. Next Generation Sequencing (NGS) is one technique that can measure one or more genetic variations as a laboratory diagnostic test, such as when used as a companion in vitro diagnostic test.

Patients with advanced cancer can have recurrent, metastatic, and/or stage IV disease. From results of clinical studies it has been shown that genetic variations in a patient’s cancer can, in concert with clinical factors, predict how each individual responds to specific treatments.

In application, a report of results of a diagnostic laboratory test using NGS (i.e., information on the cancer’s genetic variations) can contribute to predicting a patient’s response to a given drug: good, bad, or none at all. Applications of NGS to predict a patient’s response to treatment occurs ideally prior to initiation of the drug.

B. Nationally Covered Indications

Effective for services performed on or after [Month/XX] [Day/XX], [20XX]  CMS proposes that the evidence is sufficient to cover Next Generation Sequencing (NGS) as a diagnostic laboratory test, including the test results, when performed in a CLIA-certified laboratory and when ordered by a treating physician, and when both 1 and 2 are met.

1.  Patient has:

1. recurrent, metastatic, or advanced stage IV cancer; and
2. not been previously tested using the same NGS test; and
3. decided to seek further cancer treatment (e.g., therapeutic chemotherapy)

2.  The diagnostic laboratory test using NGS meets all the following criteria:

1. the test is an FDA-approved companion in vitro diagnostic; and
2. the test is used in a cancer with an FDA-approved companion diagnostic indication; and
3. the test provides an FDA-approved report of test results to the treating physician that specifies FDA-indicated treatment options for their patient’s cancer.

Results from this test must be used in the management of the patient to include guiding selection of treatments proven to improve health outcomes.

CMS proposes coverage with evidence development (CED) for NGS as a diagnostic laboratory test, including the test results, when performed in a CLIA-certified laboratory and when ordered by a treating physician and when both 1 and 2 are met.

1.  Patient has

1. recurrent, metastatic, or advanced cancer; and
2. not been previously tested using the same NGS test; and
3. decided to seek further cancer treatment (e.g., therapeutic chemotherapy).

2.  The diagnostic laboratory test using NGS meets the criteria in section a or b below:

1. The test is an FDA cleared or approved in vitro diagnostic, providing a report of test results to the treating physician who is using those results in the management of the patient’s cancer only if all the following requirements are met:
   
   
   1. The diagnostic laboratory test using NGS must be registered in the NIH Genetic Testing Registry (GTR).  All fields in the NIH GTR are required to be completed.
   
   
   2. The patient is enrolled in, and the furnishing laboratory is participating in, a prospective registry that consecutively enrolls patients, adheres to the standards of scientific integrity and relevance to the Medicare population as identified in section (B)(2)(c), and is designed to answer the following CED questions:
      
      
      • How do patient outcomes compare to either the initial clinical validation of the companion diagnostic or a cohort of controls receiving the same treatment?
      • How do the clinical characteristics of registry patients affect the clinical endpoints relative to those in initial clinical studies?
   
   
   3. The registry shall have a written executable analysis plan to address the CED questions (to appropriately address some questions, Medicare claims or other outside data may be necessary).  The registry shall make data available in a form and manner specified by CMS upon request.
   
   
   4. The registry must be able to identify the patient’s cancer type, stage, and extent of invasion and metastasis at baseline. 
   
   
   5. The registry shall track all of the following outcomes evaluated after each intervention:
      • Overall survival
      • Progression free survival
      • Objective response rate, definition must be consistent with the Response Evaluation Criteria in Solid Tumors, including definitions of minimum size of measurable lesions, instructions on how many lesions to follow, and the use of anatomical assessments for overall evaluation of tumor burden. 
      • Patient-reported outcomes using measurement developed to evaluate symptomatic toxicity in patients on cancer clinical trials.


2. The test is providing a report of test results to the treating physician who is using those results in the management of the patient’s cancer.  The diagnostic laboratory test using NGS is covered under CED only when all of the following requirements are met:
   
   
   1. The diagnostic laboratory test using NGS is provided to patients as a diagnostic test within an NIH-NCI National Clinical Trial Network clinical trial.  The trial shall adhere to the CED standards of scientific integrity and relevance to the Medicare population and identified in section (B)(2)(c), collect all data necessary, and have a written executable analysis plan and outcomes available in a form and manner specified by CMS upon request to address all of the following questions (to appropriately address some questions, Medicare claims or other outside data may be necessary):
      
      
      • How do patient outcomes compare to either the initial clinical validation of the companion diagnostic or a cohort of controls receiving the same treatment?
      • How do the clinical characteristics of registry patients affect the clinical endpoints relative to those in initial clinical studies?
   2. The diagnostic laboratory test using NGS must be registered in the NIH Genetic Testing Registry (GTR).  All fields in the NIH GTR are required to be completed.


3. All CED studies must adhere to the following standards of scientific integrity and relevance to the Medicare population:
   
   
   1. The principal purpose of the research study is to test whether a particular intervention potentially improves the participants’ health outcomes.
   2. The research study is well-supported by available scientific and medical information or it is intended to clarify or establish the health outcomes of interventions already in common clinical use.
   3. The research study does not unjustifiably duplicate existing studies.
   4. The research study design is appropriate to answer the research question being asked in the study.
   5. The research study is sponsored by an organization or individual capable of executing the proposed study successfully.
   6. The research study is in compliance with all applicable Federal regulations concerning the protection of human subjects found in the Code of Federal Regulations (CFR) at 45 CFR Part 46. If a study is regulated by the FDA, it also must be in compliance with 21 CFR Parts 50 and 56.
   7. All aspects of the research study are conducted according to the appropriate standards of scientific integrity.
   8. The research study has a written protocol that clearly addresses, or incorporates by reference, the Medicare standards.
   9. The clinical research study is not designed to exclusively test toxicity or disease pathophysiology in healthy individuals. Trials of all medical technologies measuring therapeutic outcomes as one of the objectives meet this standard only if the disease or condition being studied is life-threatening as defined in 21 CFR § 312.81(a) and the patient has no other viable treatment options.
   10. The clinical research study is registered on the www.ClinicalTrials.gov website by the principal sponsor/investigator prior to the enrollment of the first study subject.
   11. The research study protocol specifies the method and timing of public release of all pre-specified outcomes to be measured including release of outcomes if outcomes are negative or study is terminated early. The results must be made public within 24 months of the end of data collection. If a report is planned to be published in a peer-reviewed journal, then that initial release may be an abstract that meets the requirements of the International Committee of Medical Journal Editors. However, a full report of the outcomes must be made public no later than 3 years after the end of data collection.
   12. The research study protocol must explicitly discuss subpopulations affected by the treatment under investigation, particularly traditionally underrepresented groups in clinical studies, how the inclusion and exclusion criteria affect enrollment of these populations, and a plan for the retention and reporting of said populations on the trial. If the inclusion and exclusion criteria are expected to have a negative effect on the recruitment or retention of underrepresented populations, the protocol must discuss why these criteria are necessary.
   13. The research study protocol explicitly discusses how the results are or are not expected to be generalizable to the Medicare population to infer whether Medicare patients may benefit from the intervention. Separate discussions in the protocol may be necessary for populations eligible for Medicare due to age, disability or Medicaid eligibility.

Consistent with section 1142 of the Act, the Agency for Healthcare Research and Quality (AHRQ) supports clinical research studies that meet the above-listed standards and address the above-listed research questions.

C. Nationally Non-Covered Indications

CMS proposes non-coverage of NGS as a diagnostic laboratory test when patients do not have the above-noted indications for cancer or when the test does not meet the above-noted criteria.

D. Other

N/A