Recent advances in translational and personalized medicine initiatives has led to a marked increase in biomarker driven research objectives within clinical trials, thus requiring innovative mechanisms and best practices to manage biomarker specimens collected in global clinical driven trials. To truly fulfill the promise of personalized medicine, we need to incorporate, in real time, specimen metadata, clinical information, and molecular data from a trial to execute translational science. In the past, specimens were often collected from clinical trial participants, stored in a BioRepository, and accessed at some later point, long after the trial was completed. Today, biomarker and genetic research is increasingly incorporated into the trial such that specimens are utilized during the conduct of the clinical trial. This shift from a retrospective to a prospective – specimen approach requires the ability to link clinical and molecular data to the specimen. Toward that end, improved capabilities are necessary to develop integrated data sources that will inform the selection and use of clinical specimens based on clinical and scientific insight relevant to human disease. Achieving this level of integration in an era of outsourcing now requires the managing of multiple vendors to establish and track both specimen and data logistics across a network of central labs, testing labs and BioRepositories. The reward is the potential to incorporate individual clinical experience and disease relevance to drive translational studies and fulfill the promise of providing truly personalized therapies.
To meet these new objectives there is a demand to develop systems and processes to manage the requirements related to integration of consent, specimen metadata, and clinical data to transform the approaches of past generation BioRepository systems into this exciting new era. At the core of many integration efforts is the ability to design systems that allow for the association of specimens with disparate data sources at the individual subject level. It begins with informed consent for participation in a research study where participants are informed on trial information, including; data and privacy protections. The ability to protect the patient’s rights related to data and privacy, as well as, alignment with global laws and regulations, is paramount to the compliant use of collected specimens in various translational studies. Our developed systems need to be able to associate subject informed consent with all specimens collected in executed clinical studies, and align permissions/restrictions to specimens in an integrated way that allows for alignment and compliant use of specimens with specific goals of translational studies. We have also acknowledged the requirement to link the specimen metadata; (records of origin, collection, processing, and storage, quantity and quality measures) with descriptions that bring context to the collected specimens. Furthermore, the requirement to link specimens to standard clinical data (age, gender, and ethnicity), disease status, treatment and potential response/resistance to treatment will enable translational studies that are designed based on individual attributes and relevance to specific aspects of human disease. In the past, translational studies were designed on pre-clinical models that inherently have been shown to be poor predictors of effectiveness in humans. With a shift to patient centric approaches, systems that can bridge the gaps and allow researchers to utilize integrated datasets, during the conduct of the clinical trial to better understand and drive design of future studies will allow us to truly realize the promise of personalized and stratified medicine. Accordingly, effective translational research requires specimen management systems that associate all this information with molecular outcomes, but such platforms not broadly available. This represents a large unmet need and potential new market for information technology to fulfill.
Laboratory providers have, for many years, tracked specimen inventory using a variety of Laboratory Information Systems (LIMS). These systems have been the workhorse to manage internal inventories of specimens received and accessioned into their respective systems. While very useful for managing inventory and simple specimen metadata, these systems have not kept pace with information systems technology or the changing needs of the client. As we move into a period where integration of complex specimens and associated metadata are essential, challenges related to; reconciliation, complex metadata, and near real-time inventories are beginning to be addressed. To address reconciliation, there is a need for systems that can flag and initiate resolutions to discrepancies, including missing specimens, transcriptional errors, mislabeled tubes, and missing information is critical to any tracking system. Comprehensive correction should also include the resolution of downstream correction of provided data. As we collect and process complex specimens like tumor blocks, tumor slides, PBMCs, the associated metadata grows exponentially. To be able to associate this data with the specimen down to the subject level is critical to downstream stratification and utilization of distinct specimen populations. This is critical in a time where consenting practices and restrictions on genetic research can vary significantly by country and Institutional Review Boards. With the processes and systems employed today it is challenging to capture specimen inventory at the time of collection. Clinical sites are not equipped or staffed to accomplish this in our present environment with currently supported technology so it becomes even more critical for the initial receiving laboratory (usually the Central Lab) to have systems in place to rapidly accession and capture specimen data. But even as we address these challenges the biggest hurdle is the ability to interface provider systems with client systems. In many cases providers are limited to manual exporting files from LIMS systems that are limited to single trials with incomplete metadata. Central laboratory systems have generally been developed to be highly standard, to be efficient at their core business of trial management. Currently, a request for specimen data sharing are often met with the requirements for programming that includes both costs and delays in providing this critical information. The need to move from a manual export of limited information from a provider LIMS system to automated solutions that interface with next generation informatics platforms is a requirement. The power of establishing automated solutions is that specimen information can be transferred to or accessed from provider’s LIMS and become visible in a client’s system. Then cloud based access or transfers can be set up on a frequency that meets the needs of a near real-time tracking system that allows for “in-life” association and utilization of specimens in translational research. Both outsourced providers and associated clients need to work collaboratively toward seamless integration of systems which can be configurable to accommodate a variety of workflows. This will take a commitment from all parties and a level of standardization that can allow for collective formatting from the many different systems employed across our industry. An effort that can begin with providers and clients, but will need to engage the developers and suppliers of technology driven solutions in our industry to achieve a level of standardization that allows for seamless integration of systems.
In an attempt to integrate information from external provider sources (Central Labs, Testing Labs, and BioRepositories) and internal systems, we are investing in a BioRepository management system that leverages an information based infrastructure to enable integration in complex biomarker driven trials. The system allows for the tracking of complex biomarker specimens and the associated specimen metadata collected in trials, and stored at various sites around the globe. Data input and export capabilities are aligned with flexible API and integration in a platform that provides a toolbox of options that create an environment where the concept of integration is paramount. The system is central to our ability to integrate several data sources, including consent, clinical, specimen, and molecular data to drive a patient centric decision making process. The system incorporates a powerful query tool that allows stakeholders to logically integrate and associate data sources with collected specimens allowing the BioRepository to facilitate future translational studies. It is this ability to interact with multiple systems and sources that distinguishes the system from the past single dimension tracking systems. Deploying a system as described is only the first step in a workflow that includes interaction and harmonization with external providers. In this time of outsourcing and partnerships the ability to interconnect technologies and data sources with our designed systems is the key to generating true specimen and scientific insight for translational research. We still face the challenge of seamless integration of internal and external disparate data sources, but we feel our core system is well positioned to meet the demand of integration once we resolve gaps related to standardization and collective formatting.
BioRepositories are being tasked with evolving from the single dimension specimen driven banks of the past to multidimensional repositories that integrate data sources through complex information based infrastructures. Assimilation of disparate data sources from multiple external and internal databases into centralized systems that allow users to generate linkages between the specimens and comprehensive molecular and clinical data. It will be these next generation BioRepository systems that meet the evolving needs to provide an intuitive user experience that can drive greater access to, better decision making from, and foster comprehensive information around specimens that will lead to improvements in personalized therapies. The power to associate complex data, during the conduct of the clinical trial, to make timely decisions will become the norm as we move into a period of precision medicine and individualized care. Empowering clinicians and researchers to drive translational medicine trials and collaborations, based on the individualized connection between specimens and human disease to facilitate better designed trials and the promise of cutting edge translational science.