Early technology assessment of using whole genome sequencing in personalized oncology

ABSTRACT

Introduction: Personalized medicine-based treatments in advanced cancer hold the promise to offer substantial health benefits to genetic subgroups, but require efficient biomarker-based patient stratification to match the right treatment and may be expensive. Standard molecular diagnostics are currently very heterogeneous, and tests are often performed sequentially. The alternative to whole genome sequencing (WGS) i.e. simultaneously testing for all relevant DNA-based biomarkers thereby allowing immediate selection of the most optimal therapy, is more costly than current techniques. In the current implementation stage, it is important to explore the added value and cost-effectiveness of using WGS on a patient level and to assess optimal introduction of WGS on the level of the healthcare system.

Areas covered: First, an overview of current worldwide initiatives concerning the use of WGS in clinical practice for cancer diagnostics is given. Second, a comprehensive, early health technology assessment (HTA) approach of evaluating WGS in the Netherlands is described, relating to the following aspects: diagnostic value, WGS-based treatment decisions, assessment of long-term health benefits and harms, early cost-effectiveness modeling, nation-wide organization, and Ethical, Legal and Societal Implications.

Expert opinion: This study provides evidence to guide further development and implementation of WGS in clinical practice and the healthcare system.

KEYWORDS:

• Genome sequencing
• implementation
• oncology
• personalized medicine
• technology assessment

Article highlights

• A comprehensive early Health Technology Assessment approach is described to support decision making on Whole Genome Sequencing for cancer diagnostics, using the combination of real-world data, various modeling approaches, and expert elicitation to address uncertainty.

• Multidisciplinary and multi-stakeholder collaboration is necessary to analyze on the appropriate mode of implementation in the healthcare system of disruptive technologies such as Whole Genome Sequencing

• Wider use of Whole Genome Sequencing is dependent on various factors such as identification of sufficient actionable targets, evidence on the health benefit of treatments for these targets, organizational factors, Ethical, Legal and Societal Implications and cost-effectiveness.

Acknowledgments

We like to thank Inge Eekhout for the coordination of the TANGO study

Reviewers Disclosure

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Declaration of interest

MJHGS, HK, MAJ, MvdV, VMHC, EPJC have nothing to disclose. MJIJ received unrestricted research funding and consulting fees from Illumina and RTI Health Solutions. VR and WvH received unrestricted research funding from Agendia BV and Intuitive Inc.

Additional information

Funding

This work was supported by the Netherlands Organisation for Health Research and Development (ZonMw) under Grant number 846001002.