Cheng Mindy M, Palma John F, Scudder Sidney, Poulios Nick, Liesenfeld Oliver
Roche Molecular Systems, Inc., 4300 Hacienda Dr., Pleasanton, CA 94588, USA.
Roche Sequencing Solutions, 4300 Hacienda Dr., Pleasanton, CA 94588, USA.
J Pers Med. 2017 Jun 28;7(3):5. doi: 10.3390/jpm7030005.
Advances in personalized medicine are supported by companion diagnostic molecular tests. Testing accuracy is critical for selecting patients for optimal therapy and reducing treatment-related toxicity. We assessed the clinical and economic impact of inaccurate test results between laboratory developed tests (LDTs) and a US Food and Drug Administration (FDA)-approved test for detection of epidermal growth factor receptor (EGFR) mutations. Using a hypothetical US cohort of newly diagnosed metastatic non-small cell lung cancer (NSCLC) patients and EURTAC (erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer) clinical trial data, we developed a decision analytic model to estimate the probability of misclassification with LDTs compared to a FDA-approved test. We estimated the clinical and economic impact of inaccurate test results by quantifying progression-free and quality-adjusted progression-free life years (PFLYs, QAPFLYs) lost, and costs due to incorrect treatment. The base-case analysis estimated 2.3% (n = 1422) of 60,502 newly diagnosed metastatic NSCLC patients would be misclassified with LDTs compared to 1% (n = 577) with a FDA-approved test. An average of 477 and 194 PFLYs were lost among the misclassified patients tested with LDTs compared to the FDA-approved test, respectively. Aggregate treatment costs for patients tested with LDTs were approximately $7.3 million more than with the FDA-approved test, due to higher drug and adverse event costs among patients incorrectly treated with targeted therapy or chemotherapy, respectively. Invalid tests contributed to greater probability of patient misclassification and incorrect therapy. In conclusion, risks associated with inaccurate EGFR mutation tests pose marked clinical and economic consequences to society. Utilization of molecular diagnostic tests with demonstrated accuracy could help to maximize the potential of personalized medicine.
伴随诊断分子检测为个性化医疗的发展提供了支持。检测准确性对于选择接受最佳治疗的患者以及降低治疗相关毒性至关重要。我们评估了实验室自主研发检测（LDTs）与美国食品药品监督管理局（FDA）批准的用于检测表皮生长因子受体（EGFR）突变的检测之间，检测结果不准确所产生的临床和经济影响。利用美国一组新诊断的转移性非小细胞肺癌（NSCLC）患者的假设队列以及EURTAC（厄洛替尼与标准化疗作为欧洲晚期EGFR突变阳性非小细胞肺癌患者的一线治疗）临床试验数据，我们建立了一个决策分析模型，以估计与FDA批准的检测相比，LDTs出现错误分类的概率。我们通过量化无进展生存期和质量调整无进展生存年数（PFLYs，QAPFLYs）的损失以及错误治疗导致的成本，来估计检测结果不准确的临床和经济影响。基础病例分析估计，60502例新诊断的转移性NSCLC患者中，与FDA批准的检测相比，2.3%（n = 1422）会被LDTs错误分类，而FDA批准的检测为1%（n = 577）。与FDA批准的检测相比，接受LDTs检测的错误分类患者分别平均损失477和194个PFLYs。接受LDTs检测的患者的总治疗成本比接受FDA批准的检测高出约730万美元，这是因为分别接受靶向治疗或化疗的错误治疗患者的药物和不良事件成本更高。无效检测导致患者错误分类和错误治疗的可能性更大。总之，EGFR突变检测结果不准确所带来的风险给社会带来了显著的临床和经济后果。使用已证明准确性的分子诊断检测有助于最大限度地发挥个性化医疗的潜力。
