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NCI Best Practices
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Frequently Asked Questions: ForumsQuestionsDefinition of Biospecimen Resource Background on the NCI Best Practices for Biospecimen Resources Applicability and Compliance Available Resources for Implementation Costs of Implementation Biospecimen Resource Informatics Ethical, Legal, and Policy Best Practices Other Biospecimen-Related Activities and Guidelines Revisions to the NCI Best Practices Biospecimen Science Questions/AnswersHow is "biospecimen resource" defined? A biospecimen resource is defined as a collection of human specimens and associated data for research purposes, the physical structure where the collection is stored, and all relevant processes and policies. Biospecimen resources vary considerably, ranging from formal organizations to informal collections of materials in an individual researcher's freezer. What is the NCI Best Practices for Biospecimen Resources and what is its purpose? The NCI Best Practices for Biospecimen Resources (NCI Best Practices) document comprises salient principles that define state-of-the-science biospecimen resource practices, promote biospecimen and data quality, and support adherence to ethical and legal requirements. Rather than detailed laboratory procedures, the document consists of principles by which such procedures should be developed by biospecimen resources. The NCI Best Practices is intended to be adapted based on the mission and scientific needs of biospecimen resources. While adoption of the NCI Best Practices is voluntary, the Institute believes that the principles it outlines support the goal of optimizing biospecimens for cancer research. Why and how was the NCI Best Practices developed? Over the past several years, the NCI has undertaken a due diligence process to understand the state of its funded biospecimen resources and the quality of biospecimens used in cancer research. As part of this effort, a 2004 inventory of NCI-supported biospecimen resources showed substantial heterogeneity in biospecimen resource management across NCI-supported resources. This study also revealed that NCI-supported biospecimen resources were not optimized in terms of operational, legal, and ethical policies, nor are they coordinated to provide a unique resource value. In 2005, the NCI took several actions to respond to these findings in the interest of ensuring sufficient biospecimens of documented quality to support NCI-sponsored research and the findings that guide the scientific policy of the NCI. The NCI published the First-Generation Guidelines in the Federal Register on April 28, 2006, and requested public comments on the document for a 60-day period. The comments received from individuals and groups representing multiple stakeholders formed the basis of revisions to the document, which was renamed NCI Best Practices for Biospecimen Resources and published in June 2007. Does the NCI Best Practices apply to existing biospecimen resources? The NCI Best Practices is intended to be adapted, as appropriate, based on the mission and scientific needs of individual biospecimen resources, including small or independent investigator collections. Several recommendations in the NCI Best Practices can be broadly or narrowly applied depending on the mission of the biospecimen resource and/or the study design. Is compliance with the NCI Best Practices mandatory? The NCI is not a regulatory agency; thus, adoption of the NCI Best Practices is voluntary. Although the NCI cannot enforce compliance, documentation of adoption of the principles in the NCI Best Practices would demonstrate an applicant's commitment to producing biospecimens of the highest quality. Are there resources for biospecimen managers who are interested in implementing the NCI Best Practices? NCI cancer Biomedical Informatics Grid™ (caBIG™) software tools, such as caTissue Core and cancer Text Information Extraction System, or caTIES, are designed to support biospecimen resources in managing specimens in a manner recommended by the NCI Best Practices. The NCI is currently developing self-evaluation tools that will help biorepository managers identify resource strengths and weaknesses. In addition, more concrete guidance on custodianship, including considerations for research participants, investigators, and institutions; financial conflicts of interest; intellectual property; and access to products and benefits is being developed based on a 2007 custodianship symposium-workshop. In June 2007, the NCI initiated an education and outreach program targeted at investigators, biospecimen resource managers, industry representatives, hospital administrators, patient advocates, and the general public. Four forums were held in key U.S. cities to provide information about the importance of best practices in guiding biospecimen use, the operational and ethical standards in the NCI Best Practices, and resources for achieving high-quality and accessible biospecimens. The NCI Biorepositories and Biospecimen Research Branch (BBRB) also may be contacted via e-mail regarding the implementation of the NCI Best Practices at biospecimens@mail.nih.gov. What will it cost to implement the NCI Best Practices? The NCI is aware of public concerns about the cost associated with implementing the NCI Best Practices. Determining the true cost of initiating and/or maintaining a high-quality resource depends on the size, mission, and scope of each resource. In addition, the expense for most resources is "hidden" in other funding mechanisms. Thus, the first step of determining cost is to identify and analyze "modular" costs that comprise high-quality resources and apply these metrics to particular resources to determine their actual costs. The NCI Office of Biorepositories and Biospecimen Research is currently exploring various economic and cost issues related to biospecimens, including understanding the overall economic value of biospecimen resources and supporting the NCI leadership in efforts to control the costs of biospecimen resources in an era of NIH budget limitations. While acknowledging concerns about cost, the NCI maintains that investigators cannot afford the scientific impact of inadequate biospecimen handling practices; i.e., investing millions of dollars in poor-quality analytes that yield poor-quality data. What is a possible way to reduce the costs associated with implementing the NCI Best Practices? The NCI has been exploring the potential for cost recovery to supplement other support mechanisms for biospecimen resources. A reference to a cost recovery model in the NCI Best Practices (see recommendation C.4.5) emphasizes developing user fees that do not exceed cost recovery so that user fees do not become prohibitive and thereby impede research. A fee-for-service model at biospecimen resources will indirectly help defer costs back to the NCI because applicants will be able to include anticipated charges for biospecimens in their grant budgets. Besides the obvious benefits to investigators, such a practice will help the NCI gauge its investment in biobanking activities in relation to funded research. What is caBIG™? One of the most challenging areas for biospecimen resources has been the absence of information technology tools and infrastructure to facilitate the appropriate collection, processing, archiving, and dissemination of biospecimens to the research community, not only within an individual medical institution but in a network across multiple institutions. The NCI cancer Biomedical Informatics Grid (caBIG™) is an enterprise designed to create infrastructure that will facilitate the exchange of data and access to programs among cancer investigators by developing informatics tools to support the collection, annotation, storage, and dissemination of high-quality biospecimens. One of the main goals of caBIG™ is to provide guidance on uniform, nonredundant sample nomenclature for biospecimen annotation; comprehensive, technology-driven biospecimen tracking procedures; and informatics systems interoperability that will allow queries across multiple biospecimen resources or networks. These tools will be publicly available to all biospecimen resources, regardless of their source of support or scientific objectives. caBIG™ tools are designed with security considerations to support patient privacy and data access restrictions, including those aspects covered by 45 CFR Part 46 Subpart A (the "Common Rule") and the Health Insurance Portability and Accountability Act. All caBIG™ tools are free and open-source. For more information on caBIG™, visit https://cabig.nci.nih.gov. Is caBIG™ applicable to all biospecimen resources, independent of size? The NCI cancer Biomedical Informatics Grid (caBIG™) relies on a modular approach to span the cancer research landscape, which ranges from institutions with integrated, information technology staff-supported systems to those with informal or no information systems. The three prongs of the caBIG™ approach are the development of modules that address specific needs, connection through defined electronic interfaces, and use of international data standards. The focus of caBIG™ is not on the particular content of systems but rather on providing the necessary middleware infrastructure to bind together disparate and ever-evolving applications for interoperability. What caBIG™ tools are available to help manage biospecimens? The NCI cancer Biomedical Informatics Grid, or caBIG™, supports the development of informatics tools designed for biospecimen resources through the Tissue Banks and Pathology Tools Workspace (https://cabig.nci.nih.gov/workspaces/TBPT). These informatics tools include caTissue Suite, a comprehensive biospecimen management tool for inventory, tracking, and basic pathology and custom annotation, as well as the cancer Text Information Extraction System, or caTIES, which allows extraction of structured data from free-text pathology reports. Together, these tools will improve the capability for researchers across the country to select and access appropriate samples for their research. For more information on caBIG™ tools available to help manage biospecimens, visit https://cabig.nci.nih.gov/tools. What are the pathways to caBIG™ compatibility? The NCI cancer Biomedical Informatics Grid (caBIG™) Web site, found at https://cabig.nci.nih.gov/guidelines_documentation/compat_v3/, contains a section dedicated to the topic of compatibility and offers guidelines that clarify the various pathways and levels of compatibility. Multiple pathways include adopting caBIG™ tools, mapping an existing tool to caBIG™ tools, or making an existing tool caBIG™ compatible for standard reports only. Each module within caBIG™ is open source and has been carefully structured for interoperability with every other. Some specialized information technology (IT) skills are required to adopt caBIG™ tools or make an existing tool caBIG™ compatible, but installation and use do not require hiring a full-time staff or investing in an IT laboratory. Is use of caBIG™ tools mandatory for NCI-supported biospecimen resources? The NCI does not intend to make use of cancer Biomedical Informatics Grid (caBIG™) tools mandatory or for caBIG™ tools to replace commercial systems. Rather, the caBIG™ biospecimen resource management tool caTissue Suite is intended to interoperate with such systems, thus enabling electronic dialogue. caTissue Suite was designed to allow more sophisticated biospecimen tracking than simple database programs such as Excel. Is there logistical support available for existing biospecimen resources interested in upgrading their informatics system? The NCI will not dictate biospecimen resource software choices, but it does offer a process designed to help institutions identify software that will meet their needs; for example, the cancer Biomedical Informatics Grid (caBIG™) Web site has lists of functionality areas to help identify requirements and match them with various software options (for more information, visit https://cabig.nci.nih.gov/tools). Several for-profit companies also provide analysis and integration services. In addition, the new caBIG™ Enterprise Support Network (ESN) is designed to help deploy caBIG™ tools for interested resource managers. (For more information on the ESN, visit https://cabig.nci.nih.gov/esn.) When resource managers aim to build or purchase biospecimen tracking software, it is suggested that they evaluate the true costs of system development, installation, and maintenance; establish a plan for the future to ensure that the software platform is robust enough to last the lifetime of the biospecimen resource; involve end users in software development; employ use cases following a system of development methodology; and strive for Capability Maturity Model® Integration (CMMI) Level 3. Information on CMMI Level 3 is available at http://www.sei.cmu.edu/cmmi/general/general.html. Who will finance the improvement of informatics systems at existing collections? Cost concerns around upgrading informatics systems are significant. The NCI invested in developing the cancer Biomedical Informatics Grid (caBIG™) to serve the greater good of the research community. caBIG™ resources are freely available to the research community to ensure broad data sharing and collaboration and are also open source; i.e., source code is available to view, alter, and redistribute. In addition, the newly established Enterprise Support Network (ESN) is designed to help interested resource managers deploy caBIG™. (For more information on the ESN, visit https://cabig.nci.nih.gov/esn.) However, additional investments to upgrade informatics systems, which are mostly associated with implementation and infrastructure, will likely include multiple sources (e.g., academic institutions, industry, public organizations) depending on the type of resource. What recommendations do the NCI Best Practices include regarding access to biospecimens? To best serve the needs of the research community, the NCI Best Practices emphasizes the establishment of guidelines by biospecimen resources for sample distribution and clinical data sharing consistent with ethical principles, governing statutes and regulations, and-if applicable-informed consent language. Recommendations specify the applicability, scope, and content of such guidelines and stress the need for transparency. A set of general principles to guide access decisions are also provided, including scientific merit and timely, equitable, and appropriate access to biospecimens without undue administrative burden. What is the NCI doing to promote sharing of biospecimens and their data by researchers as set forth in the NCI Best Practices? One of the goals of the NCI is to break down "information silos," making important information accessible to the entire research community. Due to the labor intensiveness of the data collection process, some investigators are not motivated to share samples and data. The NCI addressed this issue by recommending in the NCI Best Practices that, consistent with the NIH Data Sharing Policy, biospecimen resources funded by the NCI have a transparent sharing policy. (For more information on the NIH Data Sharing Policy, visit http://grants.nih.gov/grants/policy/data_sharing/). In some instances, investigators may not have the information technology capability to enable sharing. The NCI cancer Biomedical Informatics Grid (caBIG™) team is developing tools that will enable valuable data and biospecimens to be shared for the collective good. Specifically, the caBIG™ is establishing an information technology (IT) infrastructure for sharing data-including biospecimen data-across a network of cancer researchers. caBIG™ also is developing vocabularies and common data elements and architecture to support other research domains. caBIG™ is engaging a variety of stakeholders ranging from institutions with integrated, IT staff-supported systems to those with informal or no information systems. What consideration has the NCI given to ethical, legal, and policy issues related to biospecimens? The NCI is highly focused on ethical, legal, and policy issues related to biospecimen resources. In 2005, the NCI convened a landmark workshop that brought together diverse representatives from the cancer research community as well as ethics, legal, and policy experts to discuss and propose approaches that could help unify, integrate, and improve biospecimen resource activities. The recommendations from this workshop, as well as additional NCI-sponsored meetings and work conducted between 2002 and 2005, formed the basis of the NCI Best Practices, which includes recommendations for biospecimen resources in the areas of custodianship, informed consent, privacy protection, access to biospecimens and data, and intellectual property and resource sharing. In October 2007, the NCI Office of Biorepositories and Biospecimen Research held a symposium-workshop, "Custodianship and Ownership Issues in Biospecimen Research," (link to workshop summary) to define the parameters of custodianship that would allow biospecimen resources to operate in a culture of transparency, fairness, and accountability to all stakeholders. Participants addressed considerations for research participants, investigators, and institutions; financial conflicts of interest; intellectual property; and access to products and benefits. The recommendations that emerged from the symposium will be used to inform the ethical, legal, and policy section of future iterations of the NCI Best Practices. How does the NCI Best Practices relate to other Government agencies and ongoing work by other organizations? The NCI does not develop regulations but it is working with other Federal agencies (e.g., the Department of Health and Human Services [HHS] Office for Human Research Protections and the U.S. Food and Drug Administration) to harmonize the NCI Best Practices with existing laws and regulations. The problem of inconsistencies between guidance from various governmental agencies has been discussed at the highest levels within the HHS; harmonization is a work-in-progress. At the level of the NIH, the Trans-NIH Bioethics Committee has formed the Human Data and Specimen Committee to address this issue. At the global level, biospecimen resource standardization efforts are underway in both the European Union and Asia. At this time, the NCI is interested in forming partnerships to educate the research community about the importance of best practices and their impact on biospecimen quality and the scientific research in which they are used. What other biospecimen guidelines or best practices are currently available? The International Society for Biological and Environmental Repositories (ISBER) published in March 2008 the second edition of ISBER Best Practices for Repositories: Collection, Storage, Retrieval, and Distribution of Biological Materials for Research, available at http://www.isber.org/Pubs/BestPractices2008.pdf. The first edition of this document, released in 2005, is heavily referenced in the NCI Best Practices and forms the basis for a number of the guidelines. The second edition has been expanded based on input from individuals within and outside ad hoc committees. The International Agency for Research on Cancer (IARC) published in 2007 the Common Minimum Technical Standards and Protocols for Biological Resource Centres Dedicated to Cancer Research. This document provides common minimum technical standards and protocols designed to stimulate the creation, development, and networking of biological resource centers at the international level. Public Responsibility in Medicine and Research (PRIM&R) also published in March 2007 a report from its Human Tissue/Specimen Banking Working Group the purpose of which was to "identify current barriers to the collection, storage, distribution, and use of human specimens and data in research, and to develop strategies for overcoming those barriers while protecting subjects" (PRIM&R Human Tissue/Specimen Banking Working Group white paper, March 2007). The white paper can be found at http://www.primr.org/ResourceCenter.aspx?id=268. Finally, the Organisation for Economic Co-operation and Development (OECD) developed in 2001, in consultation with the scientific community, the OECD Best Practice Guidelines for Biological Resource Centres. In 2008, the OECD published the Guidelines for Human Biobanks and Genetic Research Databases. How will the NCI Best Practices be updated? The NCI Best Practices is a living document that will be updated in response to evidence-based recommendations and changes in regulations. Efforts also will be made to align the NCI Best Practices, where appropriate, with biospecimen guidelines or best practices published by other organizations such as the International Society for Biological and Environmental Repositories, the International Agency for Research on Cancer, and the Organization for Economic Co-operation and Development. Periodic revision of the NCI Best Practices will occur with input from researchers, biospecimen resource managers, advocates, policymakers, and related stakeholders as changes in science, law, and policy occur. As part of the revised document, new tools and supplemental guidance in key areas will be posted to the NCI Office of Biorepositories and Biospecimen Research Web site. Is the NCI supporting research that quantifies the effects of biospecimen handling variables on biospecimen quality? The NCI Office of Biorepositories and Biospecimen Research (BBRB) has established the Biospecimen Research Network (BRN) to systematically address the impact of specific variables in individual specimen types on molecular data from given analysis platforms. The goal of the BRN is to address these issues by sponsoring, conducting, and collaborating on studies to assess the effects of human specimen preanalytical variables on the outcome of genomic and proteomic studies conducted for clinical diagnosis and cancer research purposes. To this end, the Intramural BRN Laboratory is conducting a series of research projects in collaboration with intramural and extramural collaborators. The recently launched extramural research program, "Biospecimen Research for Molecular Medicine," is designed to systematically define the impact of key preanalytical variables in human biospecimens of specific type on downstream molecular data generated from specific molecular analysis platforms and to develop innovative approaches to the control, monitoring, and assessment of biospecimen quality. Another funding opportunity within the NCI BBRB is through the Innovative Molecular Analysis Technologies, or IMAT, program, which currently has several requests for applications within its "Innovations in Cancer Sample Preparation" program. For more information on the IMAT program, visit http://imat.cancer.gov/. Is there a resource of published methods that are optimized for particular biomarkers and biospecimens? The NCI Best Practices focus on principles; details will be published in appendices, which are currently under development. Additionally, guidance concerning all levels and elements of best practices will be available on the NCI Biorepositories and Biospecimen Research Branch (BBRB) Web site in the future. Data on specific biomolecules as analyzed on specific platforms are difficult to find, often buried in the "materials and methods" sections of studies performed with other goals in mind. The NCI Biospecimen Research Network (BRN) is improving accessibility to existing evidence on how biospecimen variables affect molecular analyses via annual symposia and the Biospecimen Research Database (BRD). The BRD is a searchable Web-based tool developed in collaboration with the RAND Corporation to survey and curate the existing scientific literature for research data that define the precise relationships between biospecimen handling and the quality and reproducibility of data for cancer research. Ultimately, researchers will be able to search the BRD to find evidence-based standard operating procedures for specimen handling. The NCI also urges any researcher with pertinent biospecimen data to publish in peer-reviewed journals. In addition to awareness of the factors that will adversely affect biospecimen quality, it is important for researchers to know which factors they can disregard. Consequently, the NCI encourages members of editorial boards to value the publication of negative findings. Through the BRN, biospecimen research gaps are being identified and associated research conducted by the BBRB Intramural BRN Laboratory and new extramural programs. Molecular analysis technology development also is being supported by the NCI Innovative Molecular Analysis Technologies (IMAT) Program via a request for applications on innovative technologic solutions for biospecimens. (For more information on the IMAT program, visit http://imat.cancer.gov/.) Finally, the BRN is establishing strategic partnerships with organizations such as the College of American Pathologists (CAP) to develop data-driven, specimen-specific, platform-appropriate standard operating procedures. |
