Cost-Effectiveness of a Novel Molecular Test for Cytologically Indeterminate Thyroid Nodules

Division of Health Sciences Informatics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
The Journal of Clinical Endocrinology and Metabolism (Impact Factor: 6.21). 08/2011; 96(11):E1719-26. DOI: 10.1210/jc.2011-0459
Source: PubMed

ABSTRACT Determining which patients with thyroid nodules require surgery is limited by cytologically indeterminate findings. A new approach for preoperative molecular classification of cytologically indeterminate thyroid nodules has a reported sensitivity of 91% and specificity of 75%; however, its cost-effectiveness has yet to be assessed.
Our objective was to evaluate the 5-yr cost-effectiveness of routine use of a molecular test in adult patients with indeterminate fine-needle aspiration biopsy results from a societal perspective.
A 16-state Markov decision model was developed. Probabilities, costs, and quality-adjusted life years (QALY) were estimated from literature review, U.S. Department of Health and Human Services data, Medicare reimbursement schedules, and expert opinion.
Decision analysis of a hypothetical group of adult patients with cytologically indeterminate thyroid nodules was conducted.
Incremental cost-effectiveness ratio was calculated as incremental cost (measured in U.S. dollars) divided by incremental effectiveness (measured in QALY).
Modifying current practice with use of the molecular test resulted in 74% fewer surgeries for benign nodules with no greater number of untreated cancers. Over 5 yr, mean discounted cost estimates were $12,172 for current practice and $10,719 with the molecular test. Current practice and molecular test use produced 4.50 and 4.57 QALY, respectively.
Use of this novel molecular test for differential diagnosis of cytologically indeterminate thyroid nodules can potentially avoid almost three fourths of currently performed surgeries in patients with benign nodules. Compared with current practice based on cytological findings alone, use of this test may result in lower overall costs and modestly improved quality of life for patients with indeterminate thyroid nodules.

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    • "The combination of cytologic diagnosis and testing for the BRAFV600E mutation has improved the overall diagnostic performance of US-guided FNA.6 However, checking for the BRAFV600E mutation can cause misinterpretation due to false positive results-although this occurs rarely-as well as an elevation of medical costs.7,8 "
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    ABSTRACT: Purpose We investigated the merit of ultrasound (US) features and BRAFV600E mutation as an additional study of cytology and compared the diagnostic performances of cytology alone, cytology with US correlation, cytology with BRAFV600E mutation, and a combination of cytology, US, and BRAFV600E mutation all together. Materials and Methods This study included 185 patients (mean age, 48.4 years; range 20-77 years) with 191 thyroid nodules who underwent US-guided fine-needle aspiration (FNA) with an additional BRAFV600E mutation test. Three radiologists highly experienced in thyroid imaging retrospectively reviewed US images and classified each nodule into two categories (positive for malignancy or negative for malignancy). Interobserver variability (IOV) of US assessment between the three readers was estimated using the generalized kappa statistic of Landis and Koch. We also calculated the diagnostic performances of these studies. Results There were 131 cases of malignancy (131/191, 68.6%) and 60 cases of benign nodules (60/191, 31.4%). In terms of IOV of US assessment, the generalized kappa value was 0.242, indicating fair agreement was reached. The combination of cytology with BRAFV600E showed higher specificity (100%) and positive predictive value (PPV) (100%) compared to the combination of cytology, BRAFV600E, and US (specificity 28.3%, 66.7%, 68.3%; PPV 74.6%, 86.6%, 86.8%, respectively; p<0.001). However, cytology with BRAFV600E showed lower sensitivity (84.7%) than cytology with BRAFV600E and US (96.2%, 98.5%, 95.4%, respectively; p<0.001). Conclusion Considering the diagnostic performance and low reproducibility of US, the combination of FNA with BRAFV600E is the most reliable and objective method for diagnosing thyroid malignancy.
    Yonsei Medical Journal 07/2014; 55(4):871-8. DOI:10.3349/ymj.2014.55.4.871 · 1.29 Impact Factor
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    • "A considerable number of patients with equivocal findings are referred for surgery despite histopathological evaluation of the nodule after surgery revealing no malignancy [4]. It is estimated that around 75 000 surgeries for nodules with undetermined diagnoses are performed each year in the United States alone [8]; therefore, with a sound systematic approach, at least one third of these operations could be avoided [9]. Decision support systems that take advantage of computerized learning algorithms have been successfully applied in many areas of medicine and these have yielded diagnostic rates comparable or sometimes exceeding sophisticated diagnostic techniques and the clinical judgment of the physician [10] [11] [12] [13]. "
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    ABSTRACT: Purpose. We sought to investigate the utility of classification and regression trees (CART) classifier to differentiate benign from malignant nodules in patients referred for thyroid surgery. Methods. Clinical and demographic data of 271 patients referred to the Sadoughi Hospital during 2006–2011 were collected. In a two-step approach, a CART classifier was employed to differentiate patients with a high versus low risk of thyroid malignancy. The first step served as the screening procedure and was tailored to produce as few false negatives as possible. The second step identified those with the lowest risk of malignancy, chosen from a high risk population. Sensitivity, specificity, positive and negative predictive values (PPV and NPV) of the optimal tree were calculated. Results. In the first step, age, sex, and nodule size contributed to the optimal tree. Ultrasonographic features were employed in the second step with hypoechogenicity and/or microcalcifications yielding the highest discriminatory ability. The combined tree produced a sensitivity and specificity of 80.0% (95% CI: 29.9–98.9) and 94.1% (95% CI: 78.9–99.0), respectively. NPV and PPV were 66.7% (41.1–85.6) and 97.0% (82.5–99.8), respectively. Conclusion. CART classifier reliably identifies patients with a low risk of malignancy who can avoid unnecessary surgery.
    Journal of Thyroid Research 09/2013; 2013:983953. DOI:10.1155/2013/983953
    • "In order to avoid diagnostic surgery on benign thyroid nodules with indeterminate FNA cytopathology, pre-operative FNA-based genomics tests should predict a risk of malignancy comparable to the risk of malignancy in a cytologically benign nodule that is resected (“approximately 5% or less”).8 At this level of risk, physicians can confidently recommend clinical and sonographic monitoring in lieu of thyroid resection as they do for cytologically benign nodules under current clinical management schemas.9 Recent reviews have evaluated known gene mutation marker panels associated with thyroid malignancy and the Afirma GEC towards this end.10,11,12 "
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    ABSTRACT: Ruling out malignancy in thyroid nodules historically depended on thyroid resection and histopathological evaluation until fine needle aspiration (FNA) biopsy was introduced into the United States in the 1970's. Thyroid FNA biopsy identified a majority of thyroid nodules as benign, obviating the need for surgery in over half of the patients. However, 15%-30% of thyroid FNAs have indeterminate cytology that still requires operation, even though most of these operated nodules prove to be benign post-operatively. In order to predict which cytologically indeterminate thyroid nodules are benign and to potentially avoid surgery on these nodules, a recently described commercially available Gene Expression Classifier (GEC) test (Afirma®, Veracyte, Inc., South San Francisco, CA) has been developed that can be run on the FNA sample. This paper reviews the published literature and technology assessments/guidelines by independent parties and professional groups regarding the clinical utility as well as the analytic and clinical validity of the Afirma GEC.
    PLoS Currents 02/2013; 5. DOI:10.1371/currents.eogt.e557cbb5c7e4f66568ce582a373057e7
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