We first investigated the average diagnostic costs and the percentage of patients with a correct test result received within 2 weeks after initiation of a test strategy. The testing strategies combine a number of molecular diagnostic tests, where each test has its own specific test characteristics. In the current study, a diagnostic microsimulation model was developed to compare the cost-effectiveness of a parallel (ie, DNA- and RNA-based NGS) versus a sequential (ie, single-gene tests followed by NGS-based approaches) predictive testing strategy assuming that all patients with advanced NSCLC are tested until they are either positive for one marker, or negative for all 12 predictive markers. Therefore, effect of the timing and order of strategies requires investigation aiming to improve testing guidelines. None of these studies specified the timing and order of single-gene tests performed, although this may vary in clinical practice and affect both accuracy and TAT of a testing strategy. 5- 8 These studies found NGS strategies to detect a higher number of genetic aberrations, but differed in conclusions regarding diagnostic costs. 4 To optimize diagnostics testing, several cost-effectiveness studies have compared next-generation sequencing (NGS) DNA panels to a combination of single-gene tests, or to standard of care. In the Netherlands, a variety of predictive molecular testing strategies for patients with nonsquamous NSCLC are being used in daily clinical practice. With respect to TAT, guidelines recommend that test results should be available within 2 weeks. However, the effect of parallel and sequential test strategies on outcomes including costs, TAT, unsuccessful tests, and treatment recommendations is unclear, as it depends on many factors. These different tests can be performed either in parallel to reduce TAT, or sequentially to reduce diagnostic costs. 2 Genetic aberrations can be detected with different types of tests, which may come with different sensitivity, specificity, turnaround time (TAT), costs, as well as the number of targets assessed in a single assay. The Dutch guidelines recommend testing for 12 predictive markers to select patients who are eligible for personalized therapies. Only specific subgroups of patients who exhibit specific genetic aberrations benefit from these personalized therapies. This increases the number of patients who receive adequate personalized treatment and improves their survival and quality of life.

Optimal use of diagnostic tests contributes to correct and timely detection of genetic aberrations. Model-based analyses showed that parallel testing with next-generation sequencing–based DNA and RNA panels can improve the detection of potential druggable mutations and fusion genes, respectively, without increasing diagnostic costs.

This study compares diagnostic testing strategies in the Dutch context, to optimize the detection of druggable targets and the cost-effectiveness of molecular predictive testing. There is substantial variation in the order and type of molecular tests used for the detection of genetic aberrations for personalized treatment in patients with metastasized nonsquamous non–small-cell lung cancer. contributed equally to this work as first authors. 1Department of Epidemiology and Biostatistics, Amsterdam University Medical Center, VU Amsterdam, Amsterdam, the NetherlandsĢDepartment of Pathology, Radboudumc, Nijmegen, the NetherlandsģDepartment of Pathology, Antoni van Leeuwenhoek Hospital, the Netherlands Cancer Institute, Amsterdam, the NetherlandsĤDepartment of Pathology, Leiden University Medical Center, Leiden, the NetherlandsĥDepartment of Pulmonary Diseases, University of Groningen and University Medical Center Groningen, Groningen, the NetherlandsĦDepartment of Epidemiology, Biostatistics and HTA, Radboud University Medical Center, Nijmegen, the NetherlandsħDepartment of Pathology and Medical Biology, University Medical Center Utrecht, Utrecht University, Utrecht, the NetherlandsĨPALGA Foundation, Houten, the NetherlandsĩDepartment of Pathology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlandsġ0Department of Human Genetics, and Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlandsġ1Princess Máxima Center for Pediatric Oncology, Bilthoven, the Netherlands

Difference in cost sequential testing