Synopsis

Best Practices Forums Leads Way to Better Biospecimen Collections

For more than 100 years, physicians have been collecting blood and other tissue samples -called "biospecimens" by scientists-to detect and study disease. In the post-genomics era of biomedical science, biospecimens are assuming an even more prominent role in efforts to identify the key genes, RNAs, proteins, and signaling networks involved in cancer, and then use that information to detect cancer at its earliest stages and develop a personalized therapeutic regimen to treat that cancer. Indeed, the very future of personalized medicine depends on the ability of researchers to compare the molecular workings from hundreds of malignant and normal tissues and tease out the differences that have diagnostic and therapeutic value.

Unfortunately, the vast majority of the millions of biospecimens in collections around the world are not suitable for making the type of apples-to-apples comparisons that modern cancer biology research demands. The reason is simple: no standard protocol has governed how surgeons collect tissue samples, how pathologists prepare those biospecimens, and how tissue banks store their collected biospecimens. And, given the exquisite sensitivity of today's analytical techniques, it is nearly impossible to distinguish between molecular fingerprints related to cancer and those arising from the way a given biospecimen was handled.

To correct this problem, the National Cancer Institute (NCI) has undertaken an intensive due-diligence process to evaluate the state of its funded biospecimen resources and the quality of biospecimens used in cancer research. Based on extensive input from cancer research experts-including clinicians, scientists, ethicists, biotechnology and pharmaceutical professionals, patients, survivors, advocates, and numerous authoritative sources and regulatory bodies-NCI developed a set of standards published as the National Cancer Institute Best Practices for Biospecimen Resources. This publication defines state-of-the-science practices for acquiring tissues and fluids from research participants for two purposes: (1) promoting biospecimen and data quality and consistency and (2) encouraging adherence to the highest ethical and legal standards that support the development of new cancer interventions.

The standards articulated in NCI Best Practices are an important first step in a long process of upgrading the nation's biospecimen collections. Disseminating and gaining acceptance of these standards is the next step. Toward that end, the NCI Office of Biorepositories and Biospecimens Research (OBBR) sponsored four Biospecimen Best Practices Forums. These forums, which took place between June 2007 and January 2008 in Bethesda, Boston, Chicago, and Seattle, gave the biospecimens community not only the opportunity to learn about the technical, ethical, legal, informatics, and economic issues that became evident during development of the standards, but also the means to provide feedback to NCI as it moves forward with its biospecimen standardization process.

At each of the forums, Carolyn Compton, M.D., Ph.D., Director of OBBR, noted that NCI staff developed the Best Practices based on six operating principles:

• Evidence-based, data-driven technical and operational standards to ensure quality and enable reproducible molecular analysis
• High-quality biospecimen annotation with pathological and clinical data
• Biospecimen access through a timely, centralized peer review process
• Ethical and privacy compliance through a chain of trust with research participants
• State-of-the-art informatics systems to track biospecimens, associated data, and research participant informed consents
• Communication and outreach efforts, particularly with investigators, to ensure greatest impact.

She also noted that NCI has launched the Biospecimen Research Network to study pre-acquisition and post-acquisition variables that affect molecular profiles. In addition, the OBBR has created a searchable, Web-based database with literature related to biospecimen handling and processing. OBBR is also collaborating with other NCI strategic initiatives that require high-quality biospecimens (e.g., The Cancer Genome Atlas), forging external partnerships for expertise and implementation opportunities, coordinating biobanking practices in NCI enterprises such as the clinical trials group, and facilitating NIH and international efforts to harmonize biobanking practices.

The forums featured talks from leaders in the patient advocacy community who noted that biospecimens are precious resources, and that as a result, patients, survivors, advocates, and the general public expect that the research community will act as responsible stewards of these materials. Dovetailing with those sentiments at the forums, ethical and legal scholars remarked that the Best Practices contained significant safeguards for patient privacy while ensuring that data obtained from analyzing biospecimens were available to qualified researchers. These experts commended NCI for its efforts and remarked that the Best Practices document could easily serve as a model for biospecimen banks worldwide.

Information technology will play an important role in quality control and assurance testing of biospecimens, as well as in archiving and mining the data that will come from analyzing high-quality biospecimens. NCI's caBIG™ bioinformatics grid is well-situated to play a central organizing role in any biospecimen collection initiative. Indeed, caBIG™ has several software applications designed specifically to annotate biospecimens and store data from their analysis in easily accessible databases.

Cost is a key issue facing the adoption of standard operating procedures for biospecimen collection, annotation, and storage. The OBBR is exploring a variety of financial and cost-recovery models to develop a sustainable economic model for biospecimen banks whose research will lead to the next generation of tumor diagnostics and anticancer therapies.

The importance of adopting the Best Practices was driven home by Martin Ferguson, Ph.D., a life sciences consultant who has worked with the NCI on The Cancer Genome Atlas (TCGA) project and has followed the progress of large genomic-based discovery projects. From these experiences, Dr. Ferguson drew four conclusions. First, he noted that the quality of existing biospecimens is typically overstated by the collection holders. Second, the collection of control samples doesn't happen routinely, nor is the collection of anatomical-site-matched controls. And finally, biospecimens that are well-suited for histological examinations are not guaranteed to be of high enough quality to help in molecular analyses.

"The implementation of the NCI Best Practices can reduce such failure rates in future studies, and therefore, it is worth the up-front investment to handle biospecimens accordingly," said Dr. Ferguson. "Biospecimen banking, too often considered a sideline activity, is an exacting science. Every biospecimen protocol should be treated with the rigor of a clinical trial."

That is the goal of the NCI in releasing its Best Practices document. For more information, please visit http://biospecimens.cancer.gov/practices/ or contact the OBBR at biospecimens@mail.nih.gov.