1. Biospecimens Carolyn Compton, MD, PhD James Robb, MD Office of Biorepositories and Biospecimen Research (OBBR), NCI June 25, 2007

2. Translational Research Promises to Advance Molecular Medicine for Cancer Patients Biospecimen Distribution Biospecimen Collection Biospecimen processing and banking Molecular Data Diagnosis / Therapy PERSONALIZED CANCER CARE Biospecimen Processing and Banking

3. Molecular Research Using Human Analytes Genomics Proteomics Metabolomics All Depend On High-Quality Human Biospecimens Finding the targets for detection, therapy, prevention

4. Molecular Research and Analyte Variation Challenges for translational research using human biospecimens: Varying methods of collection, processing, and storage can alter the physical/biologic state of the specimen Varying associated specimen data elements alter what the scientist knows about the character/nature of the specimen Variable clinical information alters what the scientist knows about the patient (biologic context of the specimen) Variable restrictions (patient consent; other ethical, legal, and policy issues) alter what the scientist may do with the specimen and/or data

5. Molecular Research and Analyte Variation The lack of standardization of human biospecimens compromises the quality and the utility of molecular research and the advances in clinical medicine dependent on them.

6. The Golden Rule Garbage In  Garbage Out

7. Effects of Biospecimen Variation – Effects on clinical outcomes: Morphological artifact confounding diagnosis Skewed clinical chemistry results Potential for incorrect therapy when a therapy is linked to a diagnostic test on a biospecimen (e.g., HER2 in breast cancer) – Effects on research outcomes: Variations in gene expression data Variations in post-translational modification data Potential for misinterpretation of artefacts as biomarkers

8. Goals of NCI’s Strategic Efforts – Prepare for post-genomic changes in requirements and needs for biospecimens and biorepositories – Optimize and standardize the quality of human specimens for the research that will drive personalized cancer medicine – Ultimately remove barriers to cancer research represented by limited availability of high-quality human specimens

9. Guiding Principles of the National Biospecimen Network (NBN) Concept Premise: Standardizing biospecimen resources according to best practices will increase the quality of human biospecimens for translational research Principles of a quality virtual banking system/network – Common, best practice-based operational procedures – Common consent forms – Common material transfer agreements – Common data elements collected – Common vocabularies used – Interoperable information systems – Harmonized approaches to ethical and privacy issues

10. NCI Best Practices for Biospecimen Resources Objective :  Provide a baseline for operating standards on which to build as the state of the science evolves  Unify policies and procedures for biospecimen resources supported by the NCI or used by NCI- supported investigators  Based on state of the science as defined by 3 years of due diligence  Accepted by National Cancer Advisory Board, June 2007

11. NCI Best Practices for Biospecimen Resources Operational best practices for research biorepositories Quality assurance and quality control programs Implementation of enabling informatics systems Establishing reporting mechanisms Providing administration and management structure Ethical, legal, and policy issues Informed consent Access to specimens and data Privacy protection – HIPAA Ownership/custodianship Intellectual property Includes recommendations and guidelines for:

12. NCCCP Biospecimens: Approach Define key issues for BIOSPEC component at each site and network: – What the NCI wants - based on National Biospecimen Network concept and incorporating the NCI Best Practices for Biospecimen Resources Site-appropriate: based upon resources, staff and structures Guided by common principles and practices – What you have - key elements in place at each site – What you need – to achieve the desired outcome Create a realistic “Gap Matrix” for each site/network Include all appropriate site stakeholders, from the beginning and in all phases of the pilot: – CEO/CFO, other administrators – Surgeons – Pathologists – Nursing – Support staff (path assistants, IT support, lab personnel) – Tumor registrars – Patient advocates – Others

13. Key Issues for BIOSPECs  Site-appropriate biospecimen resource design  Adherence to common principles  Impact on existing clinical systems and personnel  Interface with clinical services  Mentoring; education; training  Annotation standardization  Informatics systems installation/retro-fitting  Key linkages: lab, path, radiology, med record, tumor registry  Ethical, legal, policy harmonization  Consents  MTAs  Institution/state-specific policy/law

14. Biospecimen Resources: Process Step One: Data gathering and education –Assess current status against implementation requirements for NCI Best practices –Educate and orient stakeholders at each site Step Two: Assessing requirements to fill gaps –Implications –Barriers –Costs –Necessary procedures and processes –Relevant infrastructure, including IT –Necessary personnel Step Three: Assessing harmonization requirements –Requirements to harmonize across networks/sites –Implications, barriers, costs, etc. Steps Within and Beyond…….? Implementation

15. BIOSPEC Checklist: Defining the Baseline Objective: To provide NCCCP with a common approach for assessing and addressing the elements required for quality biobanking Method The NCI Best Practices provided a framework and served as the primary source of quality indicators and assessment criteria Definition: A biospecimen resource is the physical plant, the specimen collection, the associated data, and all relevant procedures and policies

16. BIOSPEC Toolkit NCI Best Practices for Biospecimen Resources Baseline assessment checklist caBIG™ for Dummies Patient brochure on biospecimen donation Best Practices Road Show: national education and outreach effort –Regional meetings – Fall 2007 Boston, MA Chicago, IL Houston, TX Los Angeles, CA Seattle, WA Office of Biorepositories and Biospecimen Research (http://biospecimens.cancer.gov)http://biospecimens.cancer.gov

17. Biospecimens Carolyn Compton, MD, PhD James Robb, MD Office of Biorepositories and Biospecimen Research (OBBR), NCI June 25, 2007