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.
ThyroSeq is considered experimental/investigational E/I, 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.
- No evidence-based U.S. testing guidelines were identified that specifically address the use of ThyroSeq.
- The National Comprehensive Cancer Network (NCCN, 2017) states the following regarding molecular testing for thyroid cancer:
- “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).”
- “The NCCN Panel recommends molecular diagnostic testing for evaluating FNA results that are suspicious for follicular cell neoplasms or AUS/FLUS.”
- “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.”
- “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 of the ThyroSeq test consists of three clinical validity studies that evaluate diagnostic performance of the ThyroSeq test to detect thyroid cancer.
- In one study, the performance of the ThyroSeq test was reported as 70% (range, 46-88) sensitivity; 77% (range, 66-85), specificity 91% negative predictive value (NPV), and 42% positive predictive value (PPV). Diagnostic performance was showed to be significantly better in the Bethesda category III nodules compared to other categories (area under the curve [AUC] 0.84 vs 0.57; P=0.03).
- In a retrospective clinical validity study, sensitivity was reported as 85%, specificity as 65%, PPV as 50%, and NPV as 91%.
- A third retrospective, single-institution study reported diagnostic values as follows: sensitivity and specificity (Bethesda IV specimens) were 63 and 86%, resulting in an NPV and a PPV of 75% and 77%, respectively.
- There are currently no available clinical utility studies that evaluated the effects 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.
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Experimental/Investigational (E/I) services are not covered regardless of place of service.
ThyroSeq is typically an outpatient procedure which is only eligible for coverage as an inpatient procedure 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.
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.
