Utility and cost-effectiveness of molecular testing in thyroid nodules with indeterminate cytology.

CONTEXT: Molecular testing on biopsies from thyroid nodules with indeterminate cytology can improve patient management by preventing unnecessary surgeries on benign nodules. OBJECTIVE: The aim of the study was to determine the health outcome benefits and cost-effectiveness of molecular testing in nodules with AUS/FLUS or FN/SFN cytology. DESIGN: The initial diagnosis and treatment of a hypothetical cohort of adult U.S. patients with solitary thyroid nodules ≥1 cm was simulated by decision analytic modelling using Medicare cost estimates for three management strategies, standard of care without molecular testing (StC), gene expression classifier (GEC) and mutation and miRNA testing (MMT). RESULTS: Gene expression classifier decreased the rate of unnecessary surgeries by 32% relative to StC, yielding incremental costs of $1008 per patient or $5070 per unnecessary surgery avoided. MMT decreased the surgery rate by 67%, yielding incremental savings of -$1384 per patient or -$3170 per unnecessary surgery avoided. Results remained robust in deterministic sensitivity analyses; MMT was dominant for every variable tested. Independent of cancer prevalence, MMT yielded 52% fewer unnecessary surgeries relative to GEC #bib70% fewer two-stage thyroidectomies and correctly identified 70% more benign nodules. Test specificity had to be >68% for molecular testing to be cost-effective and decrease by >50% the rate of unnecessary surgeries performed on benign nodules. CONCLUSIONS: Molecular testing with high benign diagnostic yield can generate both positive health outcomes (less surgeries) and positive economic outputs (cost savings). These results are consistent with previously reported cost-utility data and provide valuable insights for informed decision-making by patients, physicians and payers.

Conversion, correction, and International Scale standardization: results From a Multicenter External Quality Assessment Study for BCR-ABL1 testing.

CONTEXT: Monitoring BCR-ABL1 expression levels relative to clinically validated response criteria on the International Scale (IS) is vital in the optimal management of patients with chronic myeloid leukemia, yet significant variability remains across laboratories worldwide. OBJECTIVE: To assess method performance, interlaboratory precision, and different IS standardization modalities in representative laboratories performing routine BCR-ABL1 testing. DESIGN: Fifteen blinded test specimens with 5-level nominal BCR-ABL1 to ABL1 IS percentage ratios ranging from 5% to 0.0005% and 4-level secondary IS reference panels, the ARQ IS Calibrator Panels, were tested by relative quantitative polymerase chain reaction in 15 laboratories in 5 countries. Both raw and IS percentage ratios calculated by using local conversion factors (CFs) or analytic correction parameters (CPs) were collected and analyzed. RESULTS: A total of 670 valid positive results were generated. BCR-ABL1 detection was associated with variable ABL1 quality metric passing rates (P < .001) and reached at least 0.01% in 13 laboratories. Intralaboratory precision was within 2.5-fold for all sample levels combined with a relative mean difference greater than 5-fold across laboratories. International Scale accuracy was increased by using both the CF and CP standardization methods. Classification agreement for major molecular response status was 90% after CF conversion and 93% after CP correction, with precision improved by 3-fold for the CP method. CONCLUSIONS: Despite preanalytic and analytic differences between laboratories, conversion and correction are effective IS standardization methods. Validated secondary reference materials can facilitate global diffusion of the IS without the need to perform sample exchange and improve the accuracy and precision of BCR-ABL1 quantitative measurements, including at low levels of residual disease.

Asuragen Inc.

Asuragen is a fully integrated molecular diagnostics company with products and services that incorporate cutting-edge technologies for isolating, detecting and quantifying nucleic acids. Asuragen's Signature product line offers streamlined methods for the detection of important genetic alterations and innovative RNA-based solutions for molecular oncology. The company has also pioneered research on microRNA (miRNA) function, isolation and detection in clinical samples. Asuragen is leveraging its broad intellectual property portfolio to build a significant business focused on miRNA/mRNA molecular diagnostics and pharmacogenomic/clinical laboratory molecular services. A near-term goal is to introduce next-generation miRNA-based diagnostic assays to improve tumor classification, monitor disease progression and potentially allow earlier detection of cancer. Asuragen's miRNA therapeutics development program has recently been carved off into a new sister company, Mirna Therapeutics (TX, USA).