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

Martijn J.H.G. Simons, Valesca P. Retèl, Bram L.T. Ramaekers, Rogier Butter, Joanne M. Mankor, Marthe S. Paats, Joachim G.J.V. Aerts, Zakile A. Mfumbilwa, Paul Roepman, Veerle M.H. Coupé, Carin A. Uyl-de Groot, Wim H. van Harten, Manuela A. Joore*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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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 €80,000 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 (€1534 [incremental net monetary benefit –€1349]), and SoC followed by WGS resulted in fewer QALYs (–0.002) and more costs (€1059 [–€1194]) compared with SoC alone. WGS as a diagnostic test was only cost effective if it was priced at €2000 per patient and identified 2.7% more actionable patients than SoC alone. Treating these additional identified patients with new treatments costing >€4069 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.
Original languageEnglish
Pages (from-to)1429-1442
Number of pages14
JournalPharmacoEconomics
Volume39
Issue number12
Early online date18 Aug 2021
DOIs
Publication statusPublished - Dec 2021

Bibliographical note

Funding:
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.

© 2021. The Author(s).

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