@article{931ea9dab5cc4d45bd69ae4e8d5b60fb,
title = "Early Cost Effectiveness of Whole-Genome Sequencing as a Clinical Diagnostic Test for Patients with Inoperable Stage IIIB,C/IV Non-squamous Non-small-Cell Lung Cancer",
abstract = "Background Advanced non-small-cell lung cancer (NSCLC) harbours many genetic aberrations that can be targeted with systemic treatments. Whole-genome sequencing (WGS) can simultaneously detect these (and possibly new) molecular targets. However, the exact added clinical value of WGS is unknown. Objective The objective of this study was to determine the early cost effectiveness of using WGS in diagnostic strategies compared with currently used molecular diagnostics for patients with inoperable stage IIIB,C/IV non-squamous NSCLC from a Dutch healthcare perspective. Methods A decision tree represented the diagnostic pathway, and a cohort state transition model represented disease progression. Three diagnostic strategies were modelled: standard of care (SoC) alone, WGS as a diagnostic test, and SoC followed by WGS. Treatment effectiveness was based on a systematic review. Probabilistic cost-effectiveness analyses were performed, and threshold analyses (using euro80,000 per quality-adjusted life-year [QALY]) was used to explore the early cost effectiveness of WGS. Results WGS as a diagnostic test resulted in more QALYs (0.002) and costs (euro1534 [incremental net monetary benefit -euro1349]), and SoC followed by WGS resulted in fewer QALYs (-0.002) and more costs (euro1059 [-euro1194]) compared with SoC alone. WGS as a diagnostic test was only cost effective if it was priced at euro2000 per patient and identified 2.7% more actionable patients than SoC alone. Treating these additional identified patients with new treatments costing >euro4069 per month decreased the probability of cost effectiveness. Conclusions Our analysis suggests that providing WGS as a diagnostic test is cost effective compared with SoC followed by WGS and SoC alone if costs for WGS decrease and additional patients with actionable targets are identified. This cost-effectiveness model can be used to incorporate new findings iteratively and to support ongoing decision making regarding the use of WGS in this rapidly evolving field.",
keywords = "OPEN-LABEL, PHASE-III, 1ST-LINE TREATMENT, METASTATIC CANCER, CHEMOTHERAPY, ERLOTINIB, MULTICENTER, THERAPIES, SURVIVAL, ADENOCARCINOMA",
author = "Simons, {Martijn J. H. G.} and Retel, {Valesca P.} and Ramaekers, {Bram L. T.} and Rogier Butter and Mankor, {Joanne M.} and Paats, {Marthe S.} and Aerts, {Joachim G. J.} and Mfumbilwa, {Zakile A.} and Paul Roepman and Coupe, {Veerle M. H.} and {Uyl-de Groot}, {Carin A.} and {van Harten}, {Wim H.} and Joore, {Manuela A.}",
note = "Funding Information: Bram Ramaekers, Rogier Butter, Joanne Mankor, Marthe Paats, Paul Roepman, Carin Uyl-de Groot, Wim van Harten, and Manuela Joore have no conflicts of interest that are directly relevant to the content of this article. Martijn Simons, Zakile Mfumbilwa, and Veerle Coup{\'e} have received grants from governmental funding of medical research by ZonMw. Valesca Ret{\`e}l has received grants from Agendia B.V. and Intuitive Surgical outside the submitted work. Joachim Aerts has received personal fees and non-financial support from Biocad outside the submitted work; holds stock options with Amphera; and has a patent in allogenic tumour cell lysate licensed to Amphera, combination immunotherapy in cancer pending, and biomarker for immunotherapy pending. Funding Information: This work was supported by the Netherlands Organisation for Health Research and Development (ZonMw) (grant number 846001002), the Dutch Cancer Society (KWF), and the Dutch healthcare insurance company Zilveren kruis Achmea. The funding sources had no involvement in the conduct of this research. The open access fee was paid by the Maastricht University Medical Centre and the Maastricht University. Funding Information: The authors thank Dr. Kim Monkhorst from the Netherlands Cancer Institute-Antoni van Leeuwenhoek hospital for providing expert opinion within the field of clinical pathology. The authors also thank Ms. Danalyn Byng from the Netherlands Cancer Institute-Antoni van Leeuwenhoek hospital, for providing English language editing and review support. Furthermore, the authors thank all members of the Technology Assessment of Next Generation Sequencing in Personalized Oncology (TANGO) consortium ( https://zenodo.org/communities/tango-wgs/?page=1&size=20 ) and the funding organisations the Netherlands Organisation for Health Research and Development (ZonMw) (grant numbers 846001002), the Dutch Cancer Society (KWF), and the Dutch healthcare insurance company Zilveren kruis Achmea for making this research possible. Publisher Copyright: {\textcopyright} 2021, The Author(s).",
year = "2021",
month = dec,
doi = "10.1007/s40273-021-01073-y",
language = "English",
volume = "39",
pages = "1429--1442",
journal = "Pharmacoeconomics",
issn = "1170-7690",
publisher = "Adis International Ltd",
number = "12",
}