Access to human biological materials (HBM), such as tumor tissue, blood, saliva and derivatives such as RNA and DNA, in both sufficient quantity and quality is considered one of the major bottlenecks hindering successful bench to bedside translation. However, this does not need to be the case. Cancer clinical trials offer a unique opportunity in which to collect HBM, and specimens collected in the context of large, multi-centered studies (often containing randomized treatment and control arms, administration of novel drugs and drug combinations) combined with high quality clinical data including patient follow up, provide a valuable resource that enables study designs for biomarker discovery and validation that would be difficult to fulfill from community HBM collections alone. Increasingly, clinical trials are even designed around the molecular profile of the tumor, and such molecularly driven trials require access to HBM in order to determine the exact profile of the patient.
Through collaboration and networking of multiple centers, more researchers can gain access to more HBM and thereby increase the likelihood of major breakthroughs. The EORTC structure and the nature of the studies conducted within this network provide an ideal opportunity to collect such valuable specimens. Consequently, the EORTC board has given priority to a new strategy for biobanking.
The EORTC has experience in HBM collection, and many EORTC Groups have translational research (TR) programs that regularly involve specimen collection. In addition, the EORTC has participated in specific initiatives and activities such as TubaFrost, an EU funded project designed to promote an integrated platform of human frozen tumor tissue bank, and CHEMORES, an EU funded research collaboration focused on melanoma and lung cancer for which the EORTC Headquarters Tumor Bank provides support for the HBM collection initiative. Building on these experiences, the EORTC has issued its policy for “Human Biological Materials Collection, Storage and Use” (POL020) in line with current international standards and advances in biobanking. This policy forms one pillar of an EORTC strategy to establish HBM resources that will stimulate high quality TR which, in turn, will lead to innovative clinical trials.
HMB Collection Strategy
The collection of HBM requires the implementation of minimum quality standards, and these standards must take into account the different types of HBM collections that might be considered. For example, in EORTC clinical trials we have identified two broad classes of HBM collection, materials collected for research purposes only and materials collected as part of routine clinical practice. These two classes each provide their own distinct advantages.
Type A: HBM collected for research purposes only
- Very high biological material quality criteria
- High scientific value
- Not relevant for medical routine
- Few samples fulfill quality criteria
- Strong selection bias
- Very expensive
Type B: HBM collected as part of routine clinical practice
- Variable biological material quality
- Necessary for clinical application
- Available for larger patient cohorts
- Required for biomarker validation
- Less expensive
Clearly, access to both types of samples in the context of different clinical trials places the EORTC in a strong position to pursue a full range of TR from discovery to clinical application. By assessing the specific goals of each clinical trial, and associated correlative TR studies, the most appropriate type of HBM collection for each TR project can, in future, be mapped to the one of these two types of HBM collections. However, looking forward, given that technology is ever improving and enabling more sophisticated laboratory analysis with less material, and in particular from
Type B samples such as paraffin embedded materials and blood samples, in the context of large clinical studies, Type B materials may be considered priority.
A New Model for EORTC Biobanking
In the field of biobanking, a common approach to HBM collection involving multiple centers has been to catalog individual collections of materials held over a number of institutes in a central database. This model is crucially dependent on communication between institutions and necessitates IT platforms that demand a substantial commitment to implement in the first place and subsequently to obtain the appropriate data. These challenges are compounded by the challenge of coordinating and managing a highly dispersed network of centers storing these HBM.[1]
These challenges, combined with ever increasing regulatory considerations, prompted the proposal of a new strategy for EORTC biobanking that builds on the existing expertise of the EORTC groups. The new model emphasizes the importance of physical, quality assured biobanks that would be accomplished through the allocation of an EORTC quality label to group sites that wish to store HBM. This model builds on existing infrastructures and expertise in the network but also provides expertise and support to de novo establishment of group biobanks as well as provides immediately available high quality biobanking services through an independent service provider, BioRep, Milan. This strategy will enable better support to those sites involved in EORTC biobanking by offering improved support to those centers and an economy of scale in terms of storage facilities.
The New EORTC ‘Biobanking’ Policy
EORTC Headquarters has developed this strategy into a new updated policy in collaboration with the EORTC Pathobiology Group (PBG), a group with a long standing experience in quality assurance and biobanking, the EORTC Translational Research Advisory Committee (TRAC), and the EORTC Translational Research Division (TRD). Furthermore, the EORTC Quality Assurance Committee (QAC) will be involved in reviewing and approving quality assurance processes. The policy principles are applicable to the collection, storage, and use of HBM and associated data from patients participating in EORTC clinical studies.
The updated policy promotes best practice in biobanking and is in accordance with current international legal and ethical standards for storage and future use of material. Key topics of custodianship of biological materials collected from patients enrolled in EORTC clinical studies, ethical principles of coordinating trans-border collections of HBM, confidentiality and data protection, access to HBM, establishment of EORTC group biobanks, and publication of resulting research are covered. The policy includes minimum criteria and processes by which infrastructures for storage of HBM will be assessed for EORTC accreditation.
A comprehensive multi-modality patient database
Through its HBM collection initiatives, the EORTC will be able to prospectively collect detailed data to complement its clinical and quality of life databases, its radiotherapy database, and its recently established imaging database. These resources, in toto, will add further dimensions to the analysis of endpoints in clinical trials.
Jacqueline Hall and John Bean
[1] Riegman PH, Bosch AL. OECI TuBaFrost Consortium. OECI TuBaFrost tumor biobanking. Tumori 94(2):160-163, 2008.