Molecular Testing for Thyroid Nodules of Indeterminate Cytology: A Health Technology Assessment.
Bibliographic record
Abstract
Background: The thyroid is a gland in the lower neck that is responsible for secreting hormones related to growth and metabolism. A cancer growth in the thyroid can spread to other parts of the body, but most thyroid nodules (growths) are benign, and some types of thyroid cancer are nonaggressive and can be managed with active surveillance only. We conducted a health technology assessment of molecular testing in people with thyroid nodules of indeterminate cytology, which included an evaluation of diagnostic accuracy, clinical utility, cost-effectiveness, the budget impact of publicly funding molecular testing, and patient preferences and values. Methods: We performed a systematic literature search of the clinical evidence. We assessed the risk of bias of each included study using the Risk of Bias Among Systematic Review (ROBIS) tool for systematic reviews, the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) assessment for primary studies that evaluated diagnostic accuracy, and the Risk of Bias tool for Non-randomized Studies (RoBANS) for primary studies that evaluated clinical utility. We evaluated the quality of the body of evidence according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) Working Group criteria. We performed a systematic economic literature review and conducted cost-effectiveness and cost-utility analyses with a 5-year time horizon from the Ontario Ministry of Health perspective. We also analyzed the budget impact of publicly funding molecular testing in people with thyroid nodules of indeterminate cytology in Ontario. To contextualize the potential value of molecular testing in people with thyroid nodules of indeterminate cytology, we spoke to people with thyroid nodules. Results: In the clinical evidence review, we included one systematic review, which contained eight relevant primary studies. Using molecular testing to support the rule-out of cancer in thyroid nodules of indeterminate significance may reduce the number of unnecessary surgeries. For diagnostic accuracy, molecular testing for a diagnosis of malignancy in a nodule of indeterminate significance had a sensitivity of 91% to 94% and a specificity of 68% to 82% (GRADE: Low). As well, lower rates of surgical resections were reported in nodules of indeterminate cytology (GRADE: Very Low). Compared to diagnostic lobectomy, we found that molecular testing would increase the probability of predicting a correct diagnosis, reduce the probability of unnecessary surgery, and lead to a slight improvement in quality-adjusted life-years (QALYs), but it would increase costs. The resulting incremental cost-effectiveness ratio was $220,572 to $298,653 per QALY gained. At the commonly used willingness-to-pay values of $50,000 and $100,000 per QALY gained, molecular testing was unlikely to be cost-effective (probability of molecular testing being cost-effective was less than 50%). Publicly funding molecular testing in Ontario over the next 5 years would lead to an additional cost of $6.24 million. People with thyroid nodules of indeterminate cytology reported on the benefits and drawbacks of molecular testing, as well as barriers to accessing and choosing to undergo molecular testing. Conclusions: For thyroid nodules of indeterminate cytology, molecular testing may have diagnostic accuracy as a rule-out test, and it may result in fewer nodule resections than usual care (no molecular testing). For people with thyroid nodules of indeterminate cytology, molecular testing at the current list price is unlikely to be cost-effective compared to diagnostic lobectomy. Publicly funding molecular testing in Ontario would cost about $6.24 million over the next 5 years. People with thyroid nodules of indeterminate cytology valued the information that could be provided by molecular testing, but they expressed concern about the time required to obtain results, especially if the findings were not conclusive or useful for treatment decision-making.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.089 | 0.274 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.007 | 0.015 |
| Bibliometrics | 0.020 | 0.014 |
| Science and technology studies | 0.001 | 0.002 |
| Scholarly communication | 0.006 | 0.004 |
| Open science | 0.004 | 0.004 |
| Research integrity | 0.004 | 0.003 |
| Insufficient payload (model declined to judge) | 0.003 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".