Abstract ED02-02: The importance of high-quality biospecimens to the research enterprise: The road to molecular medicine

Human biospecimens_blood, urine, and tissue samples_are the foundation of the translational research that will transform patient care. In order for meaningful progress to occur, the biospecimens used in research must meet the highest technical and ethical standards. At present, variability pervades the collection, processing, storage, and annotation of the majority of human specimens available for research. Such heterogeneous practices lead to biospecimens of unknown molecular integrity and contribute to irreproducible research results. In today's cancer medicine, the analysis of human biospecimens supports diagnosis, staging, and prognosis. Biospecimens will provide a critical link between molecular and clinical information for the personalized medicine of the future.

Providing Guidance: The NCI Best Practices for Biospecimen Resources: Over the past several years, the National Cancer Institute (NCI) has undertaken an intensive due diligence process to understand the state of its funded biospecimen resources and the quality of biospecimens used in cancer research. In 2003, the National Biospecimen Network Blueprint was published, and an extensive examination of the NCI's biospecimen resources was conducted the following year. During 2004–2005, the NCI established a trans-NCI Biorepository Coordinating Committee (BCC) and created the Office of Biorepositories and Biospecimen Research (OBBR) to lead and coordinate a strategic plan to confront and resolve biospecimen issues in a stepwise fashion. These efforts culminated in the development of the NCI Best Practices for Biospecimen Resources in June 2007. The NCI Best Practices identify salient guiding principles that define state-of-the-science biospecimen resource practices, promote biospecimen and data quality, and support adherence to ethical and legal requirements. The NCI Best Practices serve as an initial step towards harmonizing biospecimen resource practices and will be revised iteratively, with input from stakeholders.

Education and Outreach: Refining the NCI Best Practices through Stakeholder Input: The OBBR is committed to education and outreach activities in order to ensure that the NCI Best Practices remain current and state-of-the-science. In 2007 and 2008, the OBBR launched the NCI Biospecimen Best Practices Forums to educate the cancer research community about and receive feedback on the NCI Best Practices. The Forums targeted physicians, investigators, industry representatives, hospital administrators, patient advocates, and the general public. These forums provided 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. In total, over 600 people attended the series of Forums. Input obtained from stakeholders during these forums will be taken into account during the development of future versions of the NCI Best Practices and new guidance documents.

The NCI recognizes that some topics within the NCI Best Practices are difficult to resolve and will require extensive community input. In 2007 the OBBR held a workshop entitled “Custodianship and Ownership Issues in Biospecimen Research” to better define the parameters of custodianship that would allow biospecimen resources to operate in a culture of transparency, fairness, and accountability. The workshop convened experts from the academic community, private sector, patient advocacy groups, and government agencies to suggest recommendations about custodianship of biospecimens and associated data for NCI-supported biospecimen resources. Issues discussed at this workshop included: informed consent models, withdrawal of participation in research, custodial obligations for biospecimen resources, conflict of interest for resource staff, and intellectual property rights derived from research on biospecimens. The results of this workshop will be used to refine recommendations in the NCI Best Practices and provide further guidance to the cancer research community.

The quality and availability of biospecimens impacts research efforts across the biomedical enterprise. Accordingly, the OBBR is dedicated to bringing researchers together to share knowledge and develop solutions for issues relating to biospecimen quality. Approximately 300 physicians, investigators, industry representatives and patient advocates attended the March 2008 Biospecimen Research Network Symposium, “Advancing Cancer Research through Biospecimen Quality.” The meeting featured presentations and interactive discussions from a diverse group of experts who demonstrated the critical need to address biospecimen handling variables and their impact on clinical diagnoses, drug discovery, and research and development. This symposium defined both the current scientific understanding of the biology of the biospecimen and the challenges that must be met to create evidence-based standards for human biospecimen use in translational research

Developing Evidence-Based Practices: Biospecimen Research for Molecular Medicine: There is a considerable lack of scientific data assessing the effects of biospecimen handling variables on the molecular analysis of human tissues. In 2006, the OBBR received approval to establish an intramural program, the Biospecimen Research Network (BRN), to systematically address the impact of specimen handling variables on different biospecimen types and on different molecular measures. The goal of the BRN is to address these issues by sponsoring, conducting, and collaborating on studies to assess the effects of biospecimen preanalytical variables on the outcome of genomic and proteomic studies conducted for clinical diagnosis and cancer research purposes. The results of BRN research will contribute to the development of evidence-based standard operating procedures for the collection, processing, storage, and analysis of biospecimens, building on the NCI Best Practices.

In June 2007, the OBBR received approval from the NCI Board of Scientific Advisors for a new extramural funding program entitled “Biospecimen Research for Molecular Medicine” (BIOREMM) to support extramural research on biospecimen science. This funding program is intended to generate the data needed to develop state-of-the-science processes that will insure the molecular integrity and clinical relevance of biospecimens used in cancer research and clinical medicine. BIOREMM will complement the existing BRN program and will consist of a range of funding mechanisms to assess the effects of variability in handling both prior to and after the biospecimen is collected. BIOREMM will also encourage researchers to find innovative solutions and approaches to issues related to quality and reproducibility.

Bridging the Gap: Biospecimens and Disparity Issues: Evidence from a wide range of studies suggests that cancer patients diagnosed and treated in a setting of multi-specialty care and clinical research may live longer and have a better quality of life. The NCI Community Cancer Centers Program (NCCCP) will offer more Americans access to research-based cancer care in their home communities by affiliating with the hospitals and clinics where most cancer patients already receive care. During the three-year pilot phase, sites participating in the NCCCP will seek to bring the latest scientific advances and the highest level of innovative and integrated, multi-specialty care to a much larger population of cancer patients. The program is intended to complement other NCI initiatives in seeking to achieve four major goals:

• Expand clinical trials.

• Reduce cancer healthcare disparities.

• Collect, store, and share biospecimens for research.

• Explore the utility of a national database of electronic medical records.

The availability of biospecimens representing diverse communities will help accelerate our understanding of disparities in clinical outcomes and ensure that the diagnostics and treatments developed are effective for all populations. With access to a broad cross-section of cancer patients and healthy patients participating in clinical trials, researchers will have greater opportunity to study both cancerous and normal cells provided through tissue and blood samples. The pilot will also assess how the NCI Best Practices for Biospecimen Resources can be applied nationwide to benefit the entire cancer research community.

In addition to the physical quality of biospecimens, ethical, legal and social issues must also be considered. Differing social, cultural, and religious backgrounds among research participants contribute to heterogeneous views on biospecimen donation and use. Researchers and physicians must be cognizant of a donor's cultural, religious, and racial background, while also ensuring that collected biospecimens and associated information meet the highest scientific and ethical standards. Researchers and clinicians must respect the beliefs of the communities in which they work and operate transparently in order to maintain the trust of research participants.

Conclusion: Awareness of the importance of biospecimens to translational research has increased greatly and many of the collaborations necessary to advance this field have been established. Continued support and teamwork is required to fulfill the stringent requirements for high-quality and appropriately accessible biospecimens in order to advance translational research. Above all, the patient must be recognized as both an essential participant in the research process and the motivation behind advancements in cancer care.