No IMI project is an island (Guest blog)
Projects of the Innovative Medicines Initiative (IMI) are per se international endeavors, combining the efforts of different stakeholders, from patients and researchers to industry and regulators, in the healthcare sector. Development of new technologies and their implementation in clinical practice require an integrative and interdisciplinary approach to give patients timely and safe access to new diagnostics and therapies.
“Liquid Biopsy” is one of the fields that raise high hopes to improve diagnosis of a malignant disease, by showing in a blood sample early signs of therapy efficacy or early detection of developing resistance towards therapy. In the strictest sense used in oncology today, the term Liquid Biopsy is used for the enumeration of Circulating Tumor Cells (CTCs) and the analysis of circulating free tumor DNA (ctDNA). There is now a plethora of different assays at various development stages (and striving to obtain regulatory approval) for monitoring resistance against targeted therapies, or detection of druggable genomic alteration to identify patients who are more likely to respond to new classes of therapies, such as immunotherapy.
Since 2015, 40 partners from academic and clinical research to SME and big diagnostic companies have joined forces in the IMI consortium CANCER-ID (www.cancer-id.eu) to standardise and potentially support regulatory approval of Liquid Biopsies, and make them a versatile tool for diagnostics in multi-centered clinical studies for drug development and in routine clinical use. Led by two high-profile scientific key opinion leaders, Prof. Klaus Pantel (UKE, Hamburg, Germany) and Prof. Leon Terstappen (U Twente, The Netherlands), and coordinated by Bayer AG and Menarini Silicon Biosystems SpA, the focus of the consortium is on Non-Small-Cell Lung Cancer (NSCLC) and metastatic breast cancer, however, the results will have relevance for the other indications as well.
This is a bold goal which will dramatically improve patient comfort while also improving research and treatment. A goal that requires collaboration with organisations outside a research consortium with limited lifespan and resources that are planned for the project’s duration. As commercial actors in the diagnostics and pharma sectors operate globally and look for solutions that can be used everywhere, collaboration beyond Europe is also a must. CANCER-ID is therefore actively reaching out to initiatives and organizations at various levels.
- Regulators like the European Medicines Agency (EMA) and Food and Drug Administration (FDA) in the US have been approached and meetings have been organized to ask for their perspective on the need for standardized assays.
- Exchange with patient advocates such as representatives of the ESMO Patient Advocates Working Group as sought in order to gain insight into patient’s requirements for education on the topic, addressing questions of practicality in the use of Liquid Biopsy technologies and discussing access issues.
- International projects and initiatives aiming to establish best-practice documents for blood-based biomarkers like SPIDIA4P and CANCER-ID are currently working on a collaboration agreement which included liaison with the European Committee for Standardization (CEN) body “CEN/TC 140 - In vitro diagnostic medical devices” also potentially impacting on future guidelines and recommendations by the International Organization for Standardization (ISO).
- The use of standard materials for CTC and ctDNA analysis is in the scope of the UK’s National Institute for Biological Standards and Control (NIBSC) which provides also reference materials for the World Health Organization (WHO) initiatives in the genomics arena and is already active in the International Quality Network for Pathology IQNPath. CANCER-ID and NIBSC are looking into ways how some of the standards used in CANCER-ID could be produced and distributed by NIBSC in the future.
Public-Private Partnership consortia with overlapping interests in advancing the Liquid Biopsy field have been formed worldwide in recent years. Among them are the spin-off of the Cancer MoonshotSM, BloodPAC and the Foundation of the NIH (FNIH). CANCER-ID engaged with both groups, in the case of BloodPAC on harmonization of preanalytical sampling requirements, with the FNIH a deepened collaboration is currently under evaluation. The Japan Multiplex bio-Analysis Consortium, JMAC brings together multiple public and private organizations sharing an interest with CANCER-ID in blood-based miRNA analysis that is planned to result in joint consultations. More recently, first contacts have been established with a Brazilian Liquid Biopsy initiative based at the Hospital ACCamargo Cancer Centerin São Paulo.
It is one of the exciting tasks to maintain and further develop this global network of Liquid Biopsy when CANCER-ID is finishing its work at the end of 2019 and to make sure that the results can be taken forward and built upon. The Scientific Coordinator Klaus Pantel has started to establish a European Liquid Biopsy Society (ELBS) that will take over this task and hopefully bridge all Liquid Biopsy islands.