Managing a Biobank Network

Introduction

To promote translational research and the application of advances in knowledge and technology from research and development (R&D), it is very useful to build easily accessible infrastructures to facilitate rapid experimental demonstration of a hypothesis (“theory”) or to test a presimulated model. Among the many biomedical and health platforms, biobanks are one of the most attractive tools in helping to build bridges between basic, translational, clinical research, and care practice.

Typically, the collection of significant numbers of human biological samples and quality-associated information involves a major effort in planning, construction, and finally, operability, which consumes a significant amount of time and slows down the development of experimental research. Therefore, the promotion and implementation of biobanks that facilitate access to quality samples (and associated data) to researchers (that take part in a project, with the appropriate scientific organization and with the proper ethical and legal safeguards for the donor) represent an essential milestone in shortening the time that normally elapses between research and the application of its results, improving the effectiveness of the process.

For this effort to have the desired impact, constant coordination and collaboration between biobanks and conceptually related initiatives are required. Inside each organization, coordination between the different professionals involved in processing the samples and their associated information is instrumental; moreover, the overall management of these proceedings, such as identification and phenotyping of donors, sampling, processing, storage, distribution, transfer, use of samples, and associated information is necessary.

Today's biomedical research of excellence is a global phenomenon organized mainly around the study of large series of samples following well-defined and detailed criteria regarding patients' identification (with the specific information required in each case). This is especially important in the following areas:

• Processes such as cancer, where the most recent evidence shows genetic heterogeneity between patients,

All these justify the growing interest in developing cooperative networks of biobanks to minimize biases arising from heterogeneity in the quality of biological samples by means of standard procedures, development of common quality assurance policies, and promotion of collaborative environments. ¹ Therefore, an efficient effort to integrate the various information systems that manage patient identification, clinical data, and samples is required.

All around the world there are emerging a plethora of initiatives on this area,^1,2 with very different design foundations and very different expectations. It means a great and very valuable step ahead from the previous situation of very isolated collections and banks. However, more than often, these networks are being promoted by professionals without a real expertise in biobank management and/or biobank networking.

This article focuses on some basic aspects of biobank networking, including design and management (Table 1). It does not try to be an exhaustive analysis but a preliminary approach to the topic, based on 12 years of experience managing the Spanish National Tumour Bank Network promoted and coordinated by the Spanish National Cancer Centre (CNIO) ³ with >25 associated institutions. This network, a pioneer in its design, is also a part of a collaborative initiative, the Cancer Research Centres Network promoted by the Spanish Institute of Health (Instituto de Salud Carlos III), integrating several regional tumor bank networks.^4,5 Finally, the recently created Spanish National Biobank Network ⁶ also promoted by the Spanish Institute of Health and initially formed by 63 institutions has been named to be the master piece of the Spanish participation in the future pan-European Infrastructure on Biobanking BBMRI-ERIC.^1,7 Some aspects included in this article are also based on the works and discussions of the Marble Arch International Working Group on Biobanking integrated by experts in clinical biobanking from 5 continents.

Networking: When One Plus One Is More Than Two

In a globalized world, collaboration in science is essential. A clear example is translational biomedical research, where there is a need to test hypothesis and predictions formulated from in vitro studies and animal models in human samples and, finally, on clinical trials. The central role of biobanking is further strengthened by biotechnological advances, which, once implemented in some young disciplines such as molecular pathology, will create a new paradigm in the approach to genetic-based diseases such as cancer, allowing medicine to deal with new challenges in both cancer research and medical practice.

At the beginning of the century, the concept of “genome for health” emerged from the so-called translational research, meaning the transition from genomics to biology and from that to medicine. Unfortunately, the results are currently poorer than expected and promised. We require a more rapid transition, and biobanks are essential for this development. ⁸

Easy and fair access to high-quality biological samples and their associated data is, currently, the main bottleneck for the development of biological sciences research, and biobanks of excellence are the most suitable tool to resolve this bottleneck, primarily if integrated in collaborative networks. Networks are essential for obtaining and granting access to large, sometimes huge, series of harmonized cases and controls of high-quality samples and associated data, from very different locations and social communities, no matter where.

Biobanking is not a homogeneous concept and integrates diverse goals, methods, and designs.^1,9,10 The same can be said regarding biobank networking. It does integrate, at least, the following 4 basic designs:

1. Associated PROJECT-DRIVEN collections: A group of project-driven collections from different institutions with centralized or decentralized repositories. When the project is finished, the collaborative activity disappears. This is the case for most of the project-driven collaborative research consortia.

All these 4 designs are collaborative, but strictly speaking, only the last 2 categories can be considered as biobank networks.

Biobank networking following the aforementioned criteria does not null the local institutional initiative and responsibilities but add value to the system through standardization of procedures and granting access to high-complexity series.

What Does Networking Mean? The Role of the Coordination Hub

Being part of a network does not mean a loss in autonomy or personality. Being part of a network does not reduce but adds value to the associated institutions. In a well-organized and -designed network, the associated biobanks should be and feel autonomous, which means that they should feel free to participate or not in the network and/or collaborate in a specific project. Banked tissue should typically reside within the corresponding hospital, where then it can be used for teaching and research activities in each individual hospital. In other words, samples are under the custody (ownership is a controversial issue to be discussed and is outside of this publication scope) of the associated hospitals; samples “belong” to the associated hospitals, not to the network.

In a biobank network the key components are the associated biobanks. However, a well-organized coordination office is essential as a service, ¹¹ placing particular emphasis on common quality control policies, homogeneous standard operating procedures, and best practices and working as the most appropriate bridge between researchers and biobanks.

The role of the coordination office establishes a guarantee for confidentiality (double codification or end-point full-anonimization), stability, quality assurance and quality control policy, homogeneous protocols, stable recognition by research agencies, and institutional review boards. In other terms, the coordination office offers a guarantee for the associated biobanks, researchers, patients, or healthy donors.

For the most benefit and effectiveness, the leadership role of the coordination office should be based on the so-called “honest broker” design. ¹² Coordination should include leadership, but not ownership. It means service, but not hierarchy.

The main activities to be dealt by the coordination office are the implementation of a suitable quality assurance policy, the design and implementation of a common IT platform for interoperability, and an easy and scientifically robust communication with the researchers.

Quality assurance is essential for biobanking and affects samples and associated data. A quality assurance policy is more than a design of quality control; however, it is also part of it. Quality assurance management means an integrated system of management activities involving planning, implementation, documentation, assessment, and improvement to make sure that a process or item is adequate and has the quality requested for the project. Quality assurance management includes written standard operating procedures, quality indicators, goals, and controls.^13,14

IT platforms for interoperability are one of the most important and key tools in Biobank Networking Management. There are at least 2 models: A comprehensive data base including a large amount of data, or a central database based on an appropriate minimum dataset.

Both present advantages and handicaps that should be studied before establishing a definitive network design. Once again the main networking principles should be considered in parallel with practical issues.

Very frequently, the associated institutions use diverse local IT platforms for biobank management. Could a network force the use of a unique common system to its associates? Usually, the best solution is to provide a connection to an upper platform for interoperability, respecting the decision of the local associates regarding IT management platforms. This actually means to work with a minimum dataset to be assumed by all members.

Other groups are trying to build a more comprehensive central database with a huge amount of data. In this case, usually the last goal is to run meta-analysis studies based on such information. It could be very valuable, but that does not correspond to the pure definition of a network and, more importantly, if the complexity of the shared data endangers the creation and sustainability of the network in terms of cohesion and public service, it should be rejected.

The biobank network coordinator acts as a communication channel between researchers and local biobanks. This communication means more than an e-mail address or a web-page based form. It should be active and based on a scientific background. Very frequently, when the tissue request comes from basic research or from industry, the coordinator needs to open a dialog window with the customer to assist them to refine their request and its format.

In the case of preclinical researchers, the most frequent problem is the availability of the required samples. For instance, it could be better to obtain microRNAs from frozen tissue than from formalin-fixed paraffin-embedded samples; however, if the entity of study is, for instance, lung small cell carcinoma or another nonsurgical process, the availability of frozen tissue is null.

The relationship with industry includes other problems. Some companies ask for tissue and associated data to facilitate the work of their researchers and that is perfectly correct. The problem comes when, in some cases, the company tries to “buy” large amounts of tissue samples without a well-defined project, sometimes with a unique goal: to build their own biobank. In these cases, it is the coordinator's responsibility to convince the customer that a biobank is not just a “supermarket” where you can just add things to your trolley, but that biobanks attend the principle, included in several legislations, of the “minimum amount of tissue” needed for a specific project, which means that only the minimum amount of tissue really needed for the proposed project can be transferred, and the surplus, if it exists, must return to the source biobank.

The coordination hub can also offer other common services. For example:

• It can assume, promote, and/or select some laboratory facilities to elaborate or refine some final products: tissue microarrays, extracted DNA, RNA, or proteins.

From our own point of view and experience, it is extremely important for the coordination hub to assume and respect the independence of the associated institutions. They are the only ones in charge of developing their own policies with respect to several aspects such as prioritization of the access to clinical samples by preclinical investigators and/or industry and cost recovery. The coordinator can provide some advice and orientations about those topics (ie, public service oriented to the entire Scientific Community, open access vs. fairly access, differentiated fees for the services offered to their own institution, nonprofit or commercial end-users, etc.), but the final local design should be considered as one of the most important limits in the networking activity.

Networking Limits

Biobanking and biobank networking are 2 very heterogeneous concepts. Even considering exclusively human research biobanks, there are multiple designs according to the different possible goals.^9,10

One of the key concepts about biobank networking is integration. Integration should be understood at 3 different levels: local, domestic, and international. The local integration level aims to integrate all the different collections from a single institution on a unique institutional (hospital, university, research center, etc.) infrastructure of a core unit to improve all the procedures and sample security and control. Domestic integration level refers to the promotion and function of supra-institutional networks, whether regional and/or national infrastructures under specific national legislative frameworks with a public service objective, and finally, international integration level refers to incorporation into international public service infrastructures such as BBMRI or OECI-Tubafrost.^15,16

All these levels have their specific characteristics and peculiarities, and in the case of national and international networks, they include different legal frameworks and other conditionings. These peculiarities make impossible the formation of a totally uniform network, and it is always necessary to speak in terms of harmonization. For harmonization, there are 3 levels to be considered: Common aspects to share, peculiarities impossible to be normalized to, and finally, a gray zone in between.

The common aspects to share include, at least, standard operating and technical procedures and a common and well-organized quality management policy, including centralized quality control, and the most important and difficult objective to achieve is an open mind for sharing. Aspects impossible to be homogenized include very diverse local issues and, for large and international networks, restrictive institutional, regional, and/or national legislations. All these peculiarities shape the real networking limits and should be considered. The wider the scope a network has, the lesser a network can share.

An example of cited peculiarities is the advisability of common infrastructures and services. Sometimes, an independent organizational body, such as a scientific committee and IRB, could be theoretically useful but impossible to establish because of the local and institutional peculiarities. Associated network institutions prefer to maintain their own structures such as a symbol of the aforementioned independency. In those cases, the rule for the network promoter and coordinator should be to avoid conflicts and to be a meeting point more than a supraowner. Further, some national legal frameworks, such as in Spain, create difficulties for promoting central committees.

However, in our experience, there is also a gray zone in between where most possible conflicts arise from and, on the other hand, where the main role of the coordinator team resides. The true role of the coordinator team is not a passive one or a simply administrative activity. It is possible to decrease the gray zone size, translating to the daily activity the principles of harmonization based on dialog, leadership, and transparency. The cornerstone of the coordination role should be understood in terms of service to the global design and to the key pieces of the network: the associated biobanks.