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June 30, 2017 – The below citation from PubMed addresses an vey important issue associated with genetic testing in theragenomic and personalized medicine. It is the question if the genetic test used to stage, classify, or determine treatability of a disease with a given drug is accurate. Notably in the US, there are many targeted therapies that are approved and come with mandatory companion tests that are likewise approved by the regulatory authority and therefore ascertain a certain quality and reproducible accuracy of performance even when carried out in different clinical and/or diagnostic laborarory settings.
In other parts of the world, this may not always be the case. Targeted therapies may be approved and genetic testing may mandatorily be requested in order to apply these therapies to eligilbe patients, but the genetic testing itself may be left to individual clinical or diagnostic laboratories. This in itself may pose a huge risk for misdiagnoses, because genetic test are inherently prone for experimental variations and abberations when perormed in different clinical and/or diagnostic laboratories and may not always return a reliable result. The below authors have attempted to show some of the possible consequences of this situation.
Cheng MM, Palma JF, Scudder S, Poulios N, Liesenfeld O
J Pers Med 2017 Jun;7(3)
Full Text of the Article
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.