Periodic Reporting for period 2 - Instand-NGS4P (Integrated and standardized NGS workflows for Personalised therapy)
Periodo di rendicontazione: 2021-10-01 al 2025-05-31
IINtegration and STANDardized NGS workflows For Personalized therapy (Instand-NGS4P, 1.1.2020-31.5.2025 18 partners) is an R&D project funded under the Pre-Commercial Procurement (PCP) funding scheme of Horizon 2020. A major goal as defined by the European Commission was to implement next generation sequencing (NGS) in routine diagnostics for personalised medicine and scale up demand-driven innovation for healthcare systems. Although NGS is widely used in large scale research programs and the technology is well advanced there remain several challenges. These comprise user needs from patients and clinicians, requirement for regulatory compliance with the European in vitro diagnostics regulation and applicable standards as well as proper reporting for support of decision making by clinicians and providing appropriate information to patients. It is essential that the entire diagnostic workflow is addressed because the quality and reliability of the final results depend on the whole process from sample collection to producing a final diagnostic report, communicating the result to the patient and decision making. Further limiting factors include education and training of healthcare professionals, providing guidance on ethical issues related to use of NGS as well as increasing the health economic benefit to facilitate reimbursement of NGS-based diagnostics throughout health systems.
Driven by patient and clinical needs, two innovative diagnostic NGS workflows from sample-pre-analytics to supporting medical decision-making were to be developed for routine diagnostics of common and rare adult and paediatric cancers considering regulatory requirements of in vitro diagnostic medical devices (IVDs). Figure 1. Modular design in 4 Lots of the integrated NGS workflow
Driven by patient and clinical needs, two innovative diagnostic NGS workflows from sample-pre-analytics to supporting medical decision-making were to be developed for routine diagnostics of common and rare adult and paediatric cancers considering regulatory requirements of in vitro diagnostic medical devices (IVDs). Figure 1. Modular design in 4 Lots of the integrated NGS workflow
An Open Market Consultation (OMC) involving 264 external participants to align the specifications of users’ and patients’ needs with a wide stakeholder community led to the currently most comprehensive market need overview on NGS in Europe. This provided the basis for the Request for Tenders to which 24 companies and research institutions responded. After a multi-step and transparent evaluation process, 7 Solution Providers successfully completed all 3 Phases by developing innovative solutions for Lots 1, 3 and 4. No contracts were awarded to develop solutions for Lot 2 (sequencing) because only one offer was obtained for this Lot. In order to allow integration of the solutions into a standardized NGS workflow the Buyers provided their in-house sequencing platforms for testing.
The development of two CEN Technical Specifications for whole NGS workflows for medical diagnostics by CEN/TC 140 was successfully initiated.
Further supportive activities included communication and dissemination activities targeting a broad stakeholder and potential customer community, development of training and education material for healthcare professionals and patients, guidance documents for assent of minors and how to deal with incidental findings as well as health economic assessment and engagement with healthcare payers and policy makers.
Examples of main results:
o Innovative solutions to improve the sample preparation process (pre-analytics) for different sample types and analytical procedures. This markedly reduces efforts in diagnostic laboratories, reduces risks of errors and improves quality.
o Improved solutions to simplify bioinformatics data analysis to overcome the need for specialized bioinformaticians, which is essential for wider use of NGS in healthcare systems.
o Combination of analysis of cancer relevant genetic alterations and pharmacogenomic variants to increase health economic benefit from NGS testing. Every patient tested by NGS will therefore not only benefit from selection of the appropriate targeted therapy but also from improved chemotherapy and supportive medication.
o Completely new solutions for making NGS results available in a way that they can be used for therapy selection at the bedside.
o Solutions to generate reports for patients.
o Development of two European standards to provide guidance for developing and implementing NGS diagnostic workflows in health systems.
o Production of background documents for education and training of healthcare professionals as well as to inform patients about NGS.
The development of two CEN Technical Specifications for whole NGS workflows for medical diagnostics by CEN/TC 140 was successfully initiated.
Further supportive activities included communication and dissemination activities targeting a broad stakeholder and potential customer community, development of training and education material for healthcare professionals and patients, guidance documents for assent of minors and how to deal with incidental findings as well as health economic assessment and engagement with healthcare payers and policy makers.
Examples of main results:
o Innovative solutions to improve the sample preparation process (pre-analytics) for different sample types and analytical procedures. This markedly reduces efforts in diagnostic laboratories, reduces risks of errors and improves quality.
o Improved solutions to simplify bioinformatics data analysis to overcome the need for specialized bioinformaticians, which is essential for wider use of NGS in healthcare systems.
o Combination of analysis of cancer relevant genetic alterations and pharmacogenomic variants to increase health economic benefit from NGS testing. Every patient tested by NGS will therefore not only benefit from selection of the appropriate targeted therapy but also from improved chemotherapy and supportive medication.
o Completely new solutions for making NGS results available in a way that they can be used for therapy selection at the bedside.
o Solutions to generate reports for patients.
o Development of two European standards to provide guidance for developing and implementing NGS diagnostic workflows in health systems.
o Production of background documents for education and training of healthcare professionals as well as to inform patients about NGS.
The solutions developed for Lots 1, 3 and 4 bring major improvements to existing solutions or are completely new and highly innovative solutions. The modular and interoperable solutions can be combined into at least 2 different diagnostic NGS workflows covering all steps from the patient (collection of biological samples) to the patient (reporting of results and support of therapeutic decision making at the bedside). This also allows integration of new solutions into existing workflows, which markedly reduces implementation barriers. In addition, this flexibility opens the opportunity for the innovative SMEs involved to combine their solutions with products from the large market leaders (e.g. sequencing platform providers).
Another major impact of the solutions is expected by integrating cancer gene testing with pharmacogenomics information since this is still not widely implemented in medical routine diagnostics. In this context the integrated reporting of results of cancer-related alterations, pharmacogenomics variants together with information on essential prescription (e.g. e-medication) information will be a substantial improvement to achieve acceptance of innovative technologies by clinicians to support their decision making in daily cancer care. This also better exploits the power of NGS and increases the health economic benefit of NGS-based diagnostics because every patient will experience benefit either by targeted therapy or improved classical therapy including supportive medications. Improvement of the health economic benefit as to be demonstrated by future Health Technology Assessment markedly facilitates reimbursement for NGS-based diagnostics by payers thereby improving market opportunities for the manufacturers and enabling access to innovative diagnostics for patients.
Market opportunities beyond the Buyers group have been opened by a variety of supportive activities including proactive dissemination of results to the >200 leading European cancer hospitals that are members of OECI and the two ERNs that are led by two beneficiaries, presentation to the global network of directors of national cancer institutes, engagement with medical societies, presentation of results at conferences and scientific publication, dissemination in social media and engagement with policy makers in the European parliament. Furthermore, the active participation of patient advocacy groups, development of education and training materials, engagement with regulators and standardization organizations, health economic assessment and engagement with health policy makers and payers is expected to support wide implementation and usage of the solutions developed.
Some of the solutions developed are ready for IVDR conformity assessment whereas others might benefit from further improvement based on feedback from real-word environment testing performed by Buyers in Phase. It is expected that most of the solutions developed within Instand-NGS4P will be placed on the market within the next one to three years.
Another major impact of the solutions is expected by integrating cancer gene testing with pharmacogenomics information since this is still not widely implemented in medical routine diagnostics. In this context the integrated reporting of results of cancer-related alterations, pharmacogenomics variants together with information on essential prescription (e.g. e-medication) information will be a substantial improvement to achieve acceptance of innovative technologies by clinicians to support their decision making in daily cancer care. This also better exploits the power of NGS and increases the health economic benefit of NGS-based diagnostics because every patient will experience benefit either by targeted therapy or improved classical therapy including supportive medications. Improvement of the health economic benefit as to be demonstrated by future Health Technology Assessment markedly facilitates reimbursement for NGS-based diagnostics by payers thereby improving market opportunities for the manufacturers and enabling access to innovative diagnostics for patients.
Market opportunities beyond the Buyers group have been opened by a variety of supportive activities including proactive dissemination of results to the >200 leading European cancer hospitals that are members of OECI and the two ERNs that are led by two beneficiaries, presentation to the global network of directors of national cancer institutes, engagement with medical societies, presentation of results at conferences and scientific publication, dissemination in social media and engagement with policy makers in the European parliament. Furthermore, the active participation of patient advocacy groups, development of education and training materials, engagement with regulators and standardization organizations, health economic assessment and engagement with health policy makers and payers is expected to support wide implementation and usage of the solutions developed.
Some of the solutions developed are ready for IVDR conformity assessment whereas others might benefit from further improvement based on feedback from real-word environment testing performed by Buyers in Phase. It is expected that most of the solutions developed within Instand-NGS4P will be placed on the market within the next one to three years.