Castle Biosciences, Inc., Friendswood, TX.
Icahn School of Medicine at Mount Sinai, New York, NY.
Am J Dermatopathol. 2024 Dec 1;46(12):833-838. doi: 10.1097/DAD.0000000000002808. Epub 2024 Aug 14.
Comparing studies of molecular ancillary diagnostic tests for difficult-to-diagnose cutaneous melanocytic neoplasms presents a methodological challenge, given the disparate ways accuracy metrics are calculated. A recent report by Boothby-Shoemaker et al investigating the real-world accuracy of the 23-gene expression profile (23-GEP) test highlights this methodological difficulty, reporting lower accuracy than previously observed. However, their calculation method-with indeterminate test results defined as either false positive or false negative-was different than those used in previous studies. We corrected for these differences and recalculated their reported accuracy metrics in the same manner as the previous studies to enable appropriate comparison with previously published reports. This corrected analysis showed a sensitivity of 92.1% (95% confidence interval [CI], 82.1%-100%) and specificity of 94.4% (91.6%-96.9%). We then compared these results directly to previous studies with >25 benign and >25 malignant cases with outcomes and/or concordant histopathological diagnosis by ≥3 dermatopathologists. All studies assessed had enrollment imbalances of benign versus malignant patients (0.8-7.0 ratio), so balanced cohorts were resampled according to the lowest common denominator to calculate point estimates and CIs for accuracy metrics. Overall, we found no statistically significant differences in the ranges of 23-GEP sensitivity, 90.4%-96.3% (95% CI, 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 cohort from Boothby-Shoemaker et al with this unified methodological approach. Rigorous standardization of calculation methods is necessary when the goal is direct cross-study comparability.
比较用于诊断困难性皮肤黑素细胞肿瘤的分子辅助诊断检测研究具有一定的方法学挑战，因为准确性指标的计算方式存在显著差异。布斯比-舒梅克等人最近的一份报告调查了 23 基因表达谱（23-GEP）检测在现实世界中的准确性，该报告突出了这种方法学上的困难，其报告的准确性低于之前的观察结果。然而，他们的计算方法（不确定的检测结果定义为假阳性或假阴性）与之前的研究不同。我们纠正了这些差异，并按照之前的研究方法重新计算了他们报告的准确性指标，以便与之前发表的报告进行适当比较。这种校正分析显示，敏感性为 92.1%（95%置信区间[CI]，82.1%-100%），特异性为 94.4%（91.6%-96.9%）。然后，我们将这些结果与之前有>25 例良性和>25 例恶性病例的研究进行了直接比较，这些研究的结果和/或由≥3 位皮肤科病理学家进行的一致性组织病理学诊断。所有评估的研究都存在良性与恶性患者入组不平衡（0.8-7.0 比），因此根据最低共同分母对平衡队列进行了重新采样，以计算准确性指标的点估计值和 CI。总体而言，我们发现，在 23-GEP 敏感性范围（90.4%-96.3%，95%CI，80.8%-100%）、特异性范围（87.3%-96.2%，78.2%-100%）、阳性预测值范围（88.5%-96.1%，81.5%-100%）和阴性预测值范围（91.1%-96.3%，83.6%-100%）方面，之前的研究与布斯比-舒梅克等人的队列之间没有统计学上的显著差异，这种统一的方法学方法是必要的。当目标是直接跨研究比较时，需要严格规范计算方法。
