Track

Clinical Studies

Abstract

Comparing studies of ancillary diagnostic tests for equivocal cutaneous melanocytic neoplasms presents a methodological challenge, given the disparate ways accuracy metrics can be calculated. A report by Boothby-Shoemaker et al investigating the real-world accuracy of the 23-gene expression profile (23-GEP) test highlights the repercussions of this methodological disparity, reporting lower accuracy than previously observed. Their calculation method defined indeterminate test results as both false positive and false negative, which was misaligned with previous studies. Accuracy metrics were calculated using a standardized approach, which excluded indeterminate test results and reported them as a separate metric. This standardized methodology showed a sensitivity of 92.1% (95% confidence interval [CI], 82.1–100%) and specificity of 94.4% (91.6–96.9%). We compared these results directly to previous studies with >25 benign and >25 malignant cases with outcomes and/or concordant histopathological diagnosis by ≥3 dermatopathologists. These studies had the added complication of imbalances of benign vs. malignant patients, which can affect accuracy metrics; balanced cohorts were resampled to calculate point estimates and CIs for direct comparison. We found no statistically significant differences in the ranges of 23-GEP sensitivity, 90.4–96.3% (80.8–100%), specificity, 87.3–96.2% (78.2–100%), positive predictive value, 88.5–96.1% (81.5–100%), or negative predictive value, 91.1–96.3% (83.6–100%) between previous studies and the Boothby-Shoemaker et al cohort with this standardized methodology. Rigorous standardization of calculation methods is necessary and on the burden of the authors when the explicit goal is direct cross-study comparability.