Update on Activities and Priorities for Biospecimen Data Sharing Carolyn Compton, MD, PhD

1. Update on Activities and Priorities for Biospecimen Data Sharing Carolyn Compton, MD, PhD Director, Office of Biorepositories and Biospecimen Research http://biospecimens.cancer.gov caBIG™ Joint Face-to-Face Meeting CTMS, DSIC, and TBPT Workspaces November 28-30, 2006

2. NCI’s Biospecimen Issues and Challenges • Heterogeneity in biobanking practices introduces variation in biospecimens that leads to variation in analysis/research results • Data variation compromises progress in research: GIGO • Pressing needs include: • Common biorepository SOPs, standards, and management principles • Common definitions and data elements • Common access to information on specimens and cases • Common approaches to ethical, legal, and policy issues • All of these require IT infrastructural support

3. NCI’s Biospecimen Activities • First Generation Guidelines (FGGs) for NCI-supported Biorepositories published in Federal Register 2006 • NCI Office of Biorepositories and Biospecimen Research established • International Summit on Harmonization of Biorepositories conducted • caBIG™ software tools for biorepositories developed 2005 • Analysis of NCI-supported biorespositories conducted • Trans-NCI Biorepository Coordinating Committee formed 2004 • Case Studies of Existing Human Tissue Repositories published • National Biospecimen Network (NBN) Blueprint published 2003 • Internal and external review process begun • Biorepositories identified as critical for post-genomics cancer research 2002

4. NCI First Generation Guidelines • Objective: First step toward unifying policies and procedures for NCI-supported biorepositories • Status: • Posted on Federal Register and OBBR website in April 2006; • Public comment period ended July 3, 2006 • Commentary reviewed and FGGs revised by Nov. 2006 • Internal approval process in progress • Repost to Federal Register early Feb 2007 http://biospecimens.cancer.gov

5. First Generation Guidelines Overview First Generation Guidelines include recommendations for: • Common best practices for research biorepositories • Quality assurance and quality control programs • Addressing ethical, legal, and policy issues • Establishing reporting mechanisms • Providing administration and management structure • Implementation of enabling informatics systems • Specific requirement for caBIG™silver-level compatibility softened as per public comment

6. Technical and Operational Guidelines http://biospecimens.cancer.gov

7. Specimen Collection, Processing, Storage, Retrieval, and Dissemination • Handle specimens as appropriate for specimen type and study design • Minimize collection/processing time as appropriate • Develop a comprehensive Quality Management System, to include SOPs to document all protocols and a training program for all appropriate personnel • Store specimens in a stabilized state without unnecessary thawing/refreezing; dispose of specimens according to clear rules • Review and document storage equipment performance on a regular basis • Follow specimen-appropriate biosafety, packaging, and shipping procedures • Train personnel to adhere to specimen shipping regulations; control and monitor required shipping conditions. • Annotate specimens with key collection, processing, and storage data

8. Collecting/Managing Clinical Data/QA/QC • Collect and store relevant clinical and epidemiologic data associated with a specimen, including longitudinal data, if applicable.* • Comply with applicable privacy rules and human subjects regulations • Use an informatics system that tracks all aspects of collection, processing and distribution Collecting and Managing Clinical Data Quality Assurance/Quality Control • Adhere to a written Quality Management System that describes quality assurance and quality control procedures • Maintain QA/QC training records for personnel • Adhere to and periodically review SOPs • Have security systems in place, including alarms and backup power • Develop a facility disaster plan • Maintain all equipment properly, according to SOPs • Include a computerized inventory tracking system in the data management plan *A “universal” minimal clinical data set is being developed by NCI

9. Biosafety/Biorepository Informatics • Assume that all specimens are potentially infectious – provide appropriate vaccines, e.g., hepatitis • Adhere to governmental and accrediting agency requirements • Identify and address biosafety risks • Record exposure incidents and provide personnel with appropriate Rx • Establish indemnification agreements with users of biospecimens (except where prohibited by law) • Develop additional policies and procedures as appropriate for chemical, electrical, fire, occupational, and radiological safety Biosafety Biorepositry Informatics: Data Management, Inventory Control, and Tracking • Assign a unique identifier (number and/or barcode) to each specimen • Update the biorepository database each time the specimen is moved or modified • Use informatics systems that support the linking of specimens with associated data and protect the health information of patients • NCI Center for Bioinformatics guidelines and tools and caBIG™ “silver-level” compatibility is recommended

10. caBIG™ Tools for Biorepository Management caTISSUE Software Suite • caTIES (cancer Text Information Extraction System) takes information from pathology reports, and places it in structured formats that are standardized to enable different researchers and different institutions to catalog their biospecimens in a standardized way. The tool also removes the patient-identifying information from samples, to protect the privacy and confidentiality of the patient • caTISSUE core provides a systematic method to handle and track specimens, as well as to conduct administrative tasks that are essential for biorepository operations • caTISSUE Clinical Annotation Engine enables biorepositories to retrieve data from external sources – such as tumor registries and pathology laboratories – so that each biospecimen can be annotated with all the relevant molecular and clinical information Benefits • Expanded inventory of high-quality, clinically annotated specimens for molecular research • Accelerated search and access process for researchers • Ethically-based chain of trust that ensures patient privacy and confidentiality

11. Ethical, Legal, and Policy Guidelines http://biospecimens.cancer.gov

12. Informed Consent • Develop policies for handling specimens for which consent has been withdrawn • Develop clear policies for specimen and data access • Use a sample consent template • Allow research participants to specify the types of research for which their specimens may be used Develop policies for obtaining consent for studies involving children • Consider special Food & Drug Administration regulations • Establish and document transparent policies to govern the retention of records and specimens

13. Access to Biospecimens and Data • Develop clear guidelines for sample distribution and clinical data sharing (protocol-specific requirements should be met before other access is considered) • Restrict access to subjects’ identities and medical, genetic, social, and personal histories via data access system with defined privilege levels • Ensure that investigators have timely, equitable, and appropriate access, without undue administrative burden • Charge for samples only to recover costs • If a biorepository needs to close, announce the availability of specimens for transfer • Store specimens for research purposes only, not to serve individual research participants’ needs

14. Privacy Protection/Custodianship • Protect the privacy of information and follow applicable regulations • Follow documented policies on employee access to data or specimens • Provide levels of securitythat are appropriate to the type of biorepository Privacy Protection Custodianship • Plans for custodianship of collected specimens and associated data should be part of biorepository protocols • Identify and disclose financial conflicts of interest • Informed consent language should disclose that specimens may help to develop products, tests, or discoveries that may have commercial value • Develop plans to handle/dispose of specimens and associated data: • At end of the budget period of the grant • Completion of the specific research objectives of the study

15. Guidelines: Next Steps • Periodic revision will occur with input from researchers, biorepository managers, advocates, policymakers, and related stakeholders as new technologies and clinical practices emerge • OBBR’s Biospecimen Research Network will conduct research to establish evidence-based standards for collection, processing, and storage that are specific to: • Specimen type • Analysis method

16. Medical/ Surgical Procedures Restocking Unused Sample Handling/ Processing Scientific Analysis Patient Acquisition Storage Distribution Lifecycle of a Biospecimen: Biospecimen Research • Time at room temperature • Temperature of room • Type of fixative • Time in fixative • Rate of freezing • Size of aliquots • Antibiotics • Other drugs • Type of anesthesia • Duration of anesthesia • Arterial clamp time Time 0 Pre-acquisition Post-acquisition

17. Pathway to Scientifically Validated Biorepository Practices and Second Generation Guidelines

18. Update on Activities and Priorities for Biospecimen Data Sharing Office of Biorepositories and Biospecimen Research http://biospecimens.cancer.gov