Frequently Asked Questions (FAQs)

What are biospecimens?

Biospecimens are biological materials from people (such as tissue, blood, plasma, and urine) that can be used for diagnosis and basic research. When cancer patients undergo procedures such as a blood draw, biopsy or surgery in which a specimen is removed for diagnostic or therapeutic purposes, it is often possible for a small amount of residual specimen to be stored and later used for research. Many patients have given consent for their biospecimens to be used in research, in the hope that the resulting knowledge might help other patients in future years. It is important to note that such biospecimens are being collected for research purposes, not for use in transplantation or other medical products.

What are biorepositories and why are they important?

Biorepositories are “libraries” in which biospecimens are stored, either for clinical or research purposes. These biospecimens are frequently annotated with information such as demographic or clinical data about the patient from whom the biospecimen was removed. Biorepositories are critical to enabling modern molecular-based research (including genomics, proteomics, molecular imaging, etc.) that will drive the development of a new generation of targeted diagnostics and therapies (i.e., personalized medicine) to improve clinical outcomes for patients.

How are biospecimens used in research?

Since the Human Genome was mapped in 2000, scientists have developed many ways to identify genes and their functions, and to learn and alter the role they play in the origin and progression of disease. Other emerging fields of study include proteomics - the study of the full set of proteins encoded by the genome - and pharmacogenomics, which links a patient's genes to their response to drugs and medicines. All of these advances are sometimes categorized as molecular medicine.

In addition to this sort of molecular information, scientists are also analyzing a vast amount of clinical information about patients' health and disease, taken from patient records and clinical trials. This data helps them identify patterns and disease sub-types, and is leading to strategies to diagnose and treat disease in new and more effective ways. Human biospecimens can provide a bridge between emerging molecular information and clinical information. Researchers use specimens to isolate the molecular characteristics of actual human disease, and correlate those patterns with what is known about how that disease is experienced by people (the disease's clinical progression).

Commonly, human biospecimens are used to:

• Identify and validate ways to deliver drugs or agents to specific cells
• Identify how diseases progress and vary
• Group patients as more or less likely to respond to specific drugs
• Group patients to determine which treatment is appropriate
• Develop screening tests to detect biomarkers that are associated with certain stages or sub-types of a disease

Are there examples of how well-characterized biospecimens can accelerate cancer research?

Yes. Two such examples are:

• The development of trastuzumab (Herceptin®) for the treatment of breast cancer illustrates how access to well-characterized and well-preserved tissue samples can help researchers. Human epidermal growth factor receptor 2 (EGRF-2) normally controls aspects of cell growth and division. Biospecimens taken from tumors that were stored in the NCI Cooperative Breast Cancer Tissue Resource showed that EGFR-2 can be amplified in 20 to 30 percent of breast cancer cases. By knowing which cases overexpressed this problematic protein, researchers developed trastuzumab as an antibody to block this receptor. It may not have been possible to test this approach on the general breast cancer patient population. The biospecimens allowed researchers to develop a highly effective therapy targeted specifically for a sub-population of breast cancer patients.
• Gleevec® was originally developed for the treatment of a form of leukemia by targeting the BCR-ABL protein. After analyzing biospecimens collected from different tumor types, scientists discovered that a mutant form of a related protein is responsible for the progression of a rare but deadly type of cancer, gastrointestinal stromal tumors (GIST). Subsequent clinical trials showed that Gleevec was effective against GIST, and it was approved for that use by the Food and Drug Administration.

NCI and Biorepositories

How does NCI use and support biorepositories?

Because biospecimens play such a key role in cancer research, NCI has led a pioneering effort over the past five years to standardize and improve biorepositories, getting input from leaders across the cancer research community, including basic scientists, clinical oncologists, private industry, patient advocacy groups, and the bioethics and patient protection community. Building on that collective knowledge, NCI is leading a coordinated effort to develop a national biorepository infrastructure to enhance the sharing of resources. This effort has already had significant milestones:

• Developing the National Biospecimen Network Blueprint (2003)
• Analyzing NCI-supported biorepositories (2004)
• Forming a trans-NCI Biorepository Coordinating Committee (2004)
• Establishing the NCI Office of Biorepositories and Biospecimen Research (2005)
• Hosting the NCI's first International Summit on Harmonization of Biorepositories (2005)
• Issuing draft first-generation Guidelines for NCI-Supported Biorepositories (2005)
• Launching of the Biospecimen Research Network to sponsor, conduct, and collaborate on studies to assess the effects of human specimen pre-analytical variables on the outcome of genomic and proteomic studies conducted for clinical diagnosis and cancer research purposes (2005)
• Developing IT infrastructure and tools through the Cancer Biomedical Informatics Grid™ (caBIG™) to support collection, processing, archiving, and dissemination of biospecimens that are suitable for genomics-based research (2005-present)
• Revising the First Generation Guidelines for NCI-Supported Biorepositories according to public, stakeholder, and subject expert input and renaming the document the NCI Best Practices for Biospecimen Resources (2007)
• Launching an education and outreach campaign about the NCI Best Practices entitled the NCI Biospecimen Best Practices Forums (2007)
• Convening the annual Biospecimen Research Network symposium “Advancing Cancer Research Through Biospecimen Science” to highlight the significant impact of pre-analytical biospecimen variables on cancer research and molecular medicine (2008-present)

Are there NCI-sponsored research projects that use biorepositories?

There are several NCI-sponsored research initiatives and projects that draw from biorepositories, and more are planned.

• The Cancer Genome Atlas (TCGA) (see http://cancergenome.nih.gov/) is a joint initiative by NCI and the National Human Genome Research Institute (NHGRI) to broadly analyze the genomic profiles of cancer. A three-year pilot project was launched in 2006, looking at specific types of brain, lung and ovarian cancer. TCGA relies on a large, high-quality biorepository of tumor materials that can be processed into DNA and RNA. The Cancer Genome Atlas Research Network reported the first results of its large-scale, comprehensive study of the most common form of brain cancer, glioblastoma (GBM) in the Sept. 4, 2008 advance online edition of the journal Nature.
• The NCI Clinical Proteomic Technologies Initiative (see http://proteomics.cancer.gov/) is helping to optimize current proteomic technologies, while developing new technologies, reagents, systems, and working consortia that will significantly advance the field of cancer proteomics. This research requires protein lysates from tissue specimens and the initiative is developing standard methods to extract and process proteins, along with analytical tools and informatics infrastructure.

What type of research benefits from NCI biorepository programs?

NCI-supported biorepository programs support basic, epidemiologic, translational, and clinical research. Biospecimen programs collect both frozen and formalin-fixed solid tissues, blood, and other liquids, process them into molecular extracts, (such as DNA and protein), and distribute those biospecimens to support genomic and proteomic research.

What consideration has NCI given to ethical, legal, and policy issues related to biorepositories?

In addition to technical considerations, ethical and legal issues also affect the quality and accessibility of biospecimens for research. The NCI recognizes the importance of respecting research participants who contribute biospecimens and is committed to ensuring that research participants are fully informed about research activities and that all necessary privacy protections are in place. Application of the highest possible ethical standards is necessary to ensure the support and participation of patients, physicians, researchers, and others involved in biorepository activities (NBN Blueprint 2003).

Over the past 10 years, NCI has participated in, and supported, many meetings and workshops that address the issues associated with collection of biospecimens from human subjects. Forums have included events convened by NCI, Food and Drug Administration (FDA), International Society for Biological and Environmental Repositories (ISBER), and Public Responsibility in Medicine and Research (PRIM&R).

In June 2005, NCI convened a landmark workshop, bringing together leaders from the national and international academic communities, private sector, and government to provide recommendations for ethical policy guidelines that would govern the collection and use of human biological specimens and associated data in NCI-sponsored resources/repositories. The ongoing goal is to facilitate the collection and future use of specimens and associated data while protecting the subjects from whom the specimens and data are obtained. In December 2005, NCI posted the Draft First-Generation Guidelines for NCI-Supported Biorepositories to the website of the NCI Office of Biorepositories and Biospecimen Research (OBBR), now Biorepositories and Biospecimen Research Branch (BBRB). Following public comment and approval by the National Cancer Advisory Board (NCAB), the document was published as the NCI Best Practices for Biospecimen Resources (PDF Document: 202 KB). This document contains information on ethical, legal, and policy best practices for biospecimen resources, including recommendations related to informed consent, privacy protection, and access to biospecimens. The NCI will continue to refine recommendations by organizing workshops on difficult ethical and legal issues. The NCI Best Practices will be updated to reflect guidance from regulatory agencies, stakeholder input and current research in the ethics community.

What is NCI doing to ensure that informed consent is part of the biorepository process?

According to the NCI, informed consent is not only a document signed by patients who participate in research studies; rather, it is an educational process between the investigator and the prospective subject as a means to ensure respect for persons; mutual understanding of research procedures, risks, rights, and responsibilities; and continuous voluntary participation (NBN Blueprint, 2003). The NCI Best Practices for Biospecimen Resources specify that NCI-supported biorepositories should use clear and specific informed consent language to ensure that people who contribute specimens and/or data are fully informed about the purpose, risks and benefits of the proposed research. The NCI Best Practices recommend specific concepts related to biospecimen research that should be addressed in informed consent documents, depending on the nature of the research.

What is HIPAA?

HIPAA is the Health Insurance Portability and Accountability Act (see https://www.hhs.gov/hipaa/). Originally designed in the early 1990s, HIPPA is a federal regulation that standardizes electronic data exchanged within health care transactions, specifies security requirements for stored or exchanged health information, and establishes privacy regulations for health information. While HIPAA does not directly regulate the research use of biospecimens, it does include requirements for the collection and transmission of the clinical annotations that often accompany biospecimens collected for research.

What is the “Common Rule” (45-CFR-46)?

The “Common Rule” is a set of federal regulations governing patient protection for research conducted with federal funds, or at sites supported with federal funds. As a result, the Common Rule generally applies to every US academic medical center. The code describes requirements for conducting ethically sound research, such as informed consent and institutional review of research proposals. More information about the Common Rule is available at: https://www.hhs.gov/ohrp/regulations-and-policy/regulations/common-rule/.