Biospecimens

Carolyn Compton, MD, PhD

James Robb, MD

Office of Biorepositories and Biospecimen Research (OBBR), NCI

June 25, 2007

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

Molecular Research Using Human Analytes

Genomics Proteomics Metabolomics

All DependOn High-Quality

Human Biospecimens

Finding the targets for detection, therapy, prevention

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

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.

The Golden Rule

Garbage In Garbage Out

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

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

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

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

NCI Best Practices for Biospecimen Resources

• Operational best practices for research biorepositories

• Quality assurance and quality control programs

• Implementation of enabling informatics systems

• Establishing reportingmechanisms

• 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:

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

Key Issues for BIOSPECs

Site-appropriate biospecimen resource designAdherence to common principles

Impact on existing clinical systems and personnel Interface with clinical servicesMentoring; 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

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

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

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)

Biospecimens

Carolyn Compton, MD, PhD

James Robb, MD

Office of Biorepositories and Biospecimen Research (OBBR), NCI

June 25, 2007