||ThyGenX and ThyraMIR miRNA Gene Expression Classifier
||July 1, 2018
||July 2, 2018
ThyGenx and ThyraMIR miRNA Gene Expression Classifier are designed to aid in the diagnosis of thyroid nodules as either malignant or benign.
Thyroid nodules are traditionally assessed through inspection of cell cytology; however, some aspirate samples may be indeterminate. ThyraMIR uses an algorithm of 10 microRNAs previously validated using nodules with known malignancy to assist in determining if indeterminate cytology is malignant. It is used in conjunction with ThyGenX, an oncogene panel that analyzes 8 genes that are most commonly altered in thyroid cancer (papillary and follicular carcinoma).
This policy is designed to address medical guidelines that are appropriate for the majority of individuals with a particular disease, illness, or condition. Each person's unique clinical circumstances may warrant individual consideration, based on review of applicable medical records.
|Policy Position Coverage is subject to the specific terms of the member’s benefit plan.|
Use of the ThyGenx and ThyraMIR miRNA gene expression classifier to aid in the diagnosis of thyroid nodules as either malignant or benign is considered experimental/investigational, and therefore, non-covered because the safety and/or effectiveness of this service cannot be established by the available published peer-reviewed literature.
- Experimental/Investigational (E/I) molecular and genomic (MolGen) tests refer to assays involving chromosomes, DNA, RNA, or gene products that have insufficient data to determine the net health impact, which typically means there is insufficient data to support that a test accurately assesses the outcome of interest (analytical and clinical validity), significantly improves health outcomes (clinical utility), and/or performs better than an existing standard of care medical management option. Such tests are also not generally accepted as standard of care in the evaluation or management of a particular condition.
- In the case of MolGen testing, FDA clearance is not a reliable standard given the number of laboratory developed tests that currently fall outside of FDA oversight and FDA clearance often does not assess clinical utility.
|Professional Statements and Societal Positions|
· No specific evidence-based U.S. testing guidelines were identified.
· The National Comprehensive Cancer Network (NCCN, 2016) states the following regarding molecular testing for thyroid cancer:
o “The diagnosis of follicular carcinoma requires evidence of either vascular or capsular invasion, which cannot be determined by FNA. Molecular diagnostics (category 2B) may be useful to allow reclassification of follicular lesions (follicular neoplasm or follicular lesions of undetermined significance (FLUS)) as either more or less likely to be benign or malignant based on genetic profile. If molecular testing (category 2B) in conjunction with clinical and ultrasound features suggests papillary thyroid carcinoma, especially in the case of BRAF V600E, see (PAP-1). Use molecular markers with caution and caveat).”
o “Molecular diagnostic testing may include multigene assays (e.g. the gene expression classifier) or individual mutational analysis. The gene expression classifier measures the expression of at least 140 genes.”
o “BRAF V600E mutation analysis was recommended by some panelists for the evaluation of thyroid nodules (not restricted to the follicular lesions).”
· The current evidence base consists of two analytical validity studies and two clinical validity studies.
o Clinical validity studies reported area under the receiver operator curve (AUC) values ranging from 0.89 to 0.94; the test correctly classified 92% of benign lesions as low risk or negative and correctly classified 92% of malignant lesions as high risk or positive.
o Another study reported that ThyraMIR correctly identified 64% of malignant lesions and 96% of benign lesions. The sensitivity and specificity of the test was reported as 89% (95% confidence interval [CI], 73-97%) and 85% (95% CI, 75-92%), respectively. With a 32% prevalence rate, 61% of the results were considered benign, generating a negative predictive value (NPV) of 94% (95% CI, 85-98%).
· Preliminary clinical validity studies indicate reasonable diagnostic accuracy; however, additional studies are needed to confirm these early findings. Furthermore, there are currently no available clinical utility studies that evaluated the effects of on patient-relevant outcomes (survival, quality of life). Additional research is necessary to assess how testing will be used in the disease management of patients with thyroid cancer.
|Place of Service: Outpatient|
ThyGenx and ThyraMIR miRNA gene expression classifier are typically outpatient procedures which are only eligible for coverage as inpatient procedures in special circumstances, including, but not limited to, the presence of a co-morbid condition that would require monitoring in a more controlled environment such as the inpatient setting.
ThyGenx and ThyraMIR miRNA gene expression classifier are considered experimental/investigational and, therefore, non-covered and applies to Facility claims.
|The policy position applies to all commercial lines of business|
Services that do not meet the criteria of this policy will be considered experimental/investigational (E/I). A network provider can bill the member for the experimental/investigational service. The provider must give advance written notice informing the member that the service has been deemed E/I. The member must be provided with an estimate of the cost and the member must agree in writing to assume financial responsibility in advance of receiving the service. The signed agreement must be maintained in the provider’s records.
Medical policies do not constitute medical advice, nor are they intended to govern the practice of medicine. They are intended to reflect Highmark's reimbursement and coverage guidelines. Coverage for services may vary for individual members, based on the terms of the benefit contract.
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