# Presentation: 003394

## The Biospecimen Research Network

**The Biospecimen Research Network**
**and**
**RAND Survey of Biospecimen Literature**
- Helen Moore, PhD
**http://biospecimens.cancer.gov**

- November 30, 2006

## Lifecycle of a Biospecimen: Biospecimen Research

**Lifecycle of a Biospecimen: Biospecimen Research**

**Time 0**

**Post-acquisition**

**Pre-acquisition**

**The specimen is viable**

## Lifecycle of a Biospecimen: Biospecimen Research

**Post-acquisition variables:**
**Time at room temperature**
**Temperature of room**
**Type of preservative**
**Time in preservative**
**Rate of freezing**
**Size of aliquots**
**Type of collection container**
**Biomolecule extraction method**
**Storage temperature**
**Storage duration**
**Storage in vacuum**

**Pre-acquisition variables:**
**Antibiotics**
**Other drugs**
**Type of anesthesia**
**Duration of anesthesia**
**Arterial clamp time**
**Blood pressure variations**
**Intra-op blood loss**
**Intra-op blood administration**
**Intra-op fluid administration**
**Pre-existing medical conditions**
**Patient gender**

## Effects of Biospecimen variables

- Effects on clinical outcomes:
- Morphological analysis/diagnosis
- Skewed clinical chemistry results
- Potential for incorrect therapy when diagnostic is paired with therapeutic (e.g., HER2)
- Effects on research outcomes:
- Variations in gene expression
- Variations in post-translational modification (e.g., phosphorylation status)
- Potential for misinterpretation of artefacts as biomarkers

## Biospecimen Research Network (BRN)

- Produce scientific evidence for guiding development of data-driven SOPs for collection, processing, storage and analysis of specimens.
- Provide leadership to stimulate investment in biospecimen science development.
*What needs to be done? Informed by:*
*Summer 2005 NCI workshops on Biospecimen issues*
*March 2006 OBBR Biospecimen Research Symposium*
*Built on several months of individual meetings with more than 100 investigators from the National Institutes of Health (NIH) intramural program and other Government, academic, and commercial research organizations*
*Clinicians and scientists from the intramural and extramural community with the collective expertise to carry out complex BRN research projects*

## Biospecimen Research Network:An Integral Part of the OBBR Guidelines Program

- Develop and foster state-of-the-science methods to assess, improve, and assure the quality of biorepositories funded by the NCI.
- First Generation Guidelines for NCI-Supported Biorepositories
**RAND literature review of biospecimen science publications**
**BRN: generation of new data in biospecimen science**
- Collaboration with authoritative professional organizations on data-driven protocol development (e.g., College of American Pathologists)
- Step-wise development of evidence-based Second Generation Guidelines
- Development of objective biorepository evaluation criteria

## Primary customers of BRN results 

- TCGA (biospecimen factors influencing DNA/chromatin/RNA quality and utility for downstream analysis techniques; to include blood and blood products, and tissues)
- CPTAC (biospecimen factors influencing proteomics analysis of blood and blood products, and tissues)
- FDA/Clinical trials community (biospecimen factors influencing clinical diagnostic tests for personalized cancer therapies)
- Cancer research community (biospecimen factors influencing the results and conclusions of targeted studies on cancer tissues, blood, and body fluids)
- Biorepository community (biospecimen factors influencing collection, processing and storage of cancer tissues, blood, and body fluids for multiple uses)
- Epidemiological research community (biospecimen factors influencing collection, processing and storage of cancer tissues, blood, and body fluids for long-term studies)

## BRN: “Wet” Research

- Program Features:
- Interdisciplinary Research with focus on emerging technologies for cancer
- Controlled tissue acquisition
- Controlled molecular isolation and analysis
- Vision of BRN:
- A network of partners (intramural, extramural, military, professional, and industrial)
- Plan and execute prospective studies
- Determine how the results of DNA, RNA and protein analysis are affected by defined pre-acquisition and post-acquisition specimen variables
- Advisory assistance of scientific experts in tissue acquisition and biomolecule analysis

## BRN Pilot Projects 

- Indivumed- Colon cancer ischemia tissue gene expression
- Urologic Oncology- Renal cell carcinoma DNA and ischemia gene expression
- Kevin Camphausen- Urine VEGF
- WRAMC- Breast ER, PR, HER-2/neu
- Milestone Medical- Recovery of RNA and proteins from FineFix-fixed tissue
- LCM and cDNA core facilities- Comparison of recovery of RNA and proteins from tissue using different laser microdissection platforms

## Central themes of BRN research

- “Bridging the gap” between existing clinical practice for biospecimens and emerging technologies for personalized diagnostics and therapies
- Tissue preservation variables and their impact on downstream applications (e.g., HER2)
- Robotic surgery vs. manual surgery for prostate – are tissues harvested from robotic surgery suitable for advanced biomarker detection?
- Defining the most significant variables for prospective collection of tissues, blood, and body fluids
- Effects of pre-acquisition variables and biomolecule extraction methods on biomolecule analysis results in blood
- Developing evidence-based biospecimen quality indicators for specific analytical platforms
- In conjunction with above study, with accepted proper and improper conditions for collection and biomolecule analysis in blood

## “Dry” Research: RAND survey

- Comprehensive assessment of the existing published and unpublished information on biospecimen research studies
- Basis of gap analysis: What important biospecimen research remains to be done?
- Potential as a central resource for the biobanking community
*Type of resource? Book?*
***Develop a searchable website of biospecimen research data***

## Software development for RAND survey

***Literature curation tool and database to populate a publicly available, searchable biospecimen science website***
- Future home of prospective BRN research and Protocols
- Developed in collaboration with NCICB (Ian Fore)
- Two user groups:
- Literature curators (RAND)
- Future web site users

## Software development for RAND survey

- Two use cases:
- Curator reads paper and records ***relevant*** information to database
- User visits the BRN website and searches for ***relevant*** studies to advise development of their research protocols
*What’s “relevant”?*
*How to structure the data?*
*What’s the right terminology?*

## Software development for RAND survey

**Concepts**:
- Different “Studies” can underlie a paper
- Different types of information:
- General information about the Biospecimen
- Biomolecules isolated from a Biospecimen
- Technology platforms used to analyze the Biomolecules
- Experimental factors that were the subject of the research study
**Terminology “compromises”**:
- Example: “Diagnosis” data field
- Different user groups (Pathologist vs. Proteomics researcher)
- Surveyed literature may be broader than cancer
- What’s logical? (and simple?)

## Software development for RAND survey

**Staged development approach**:
- Development of data model in Excel
- Design of oracle database and web interface
- Pilot project in MS Access prototype
- Web development advised by pilot results

## Sample screenshots

## Sample screenshots

## Sample screenshots

## Sample screenshots

## Development of Searchable Website for Guidelines, BRN, RAND

- Milestones:
- July 2006-July 2007 – RAND study, phase 1
- July 2006
- Begin meetings with RAND introducing idea of web-based curation
- Kickoff of web development project with developer staff procured through caBIG organization
- August 2006
- Development of appropriate forms for data entry by RAND curators
- Web site prototype development
- November 2006
- Pilot project with MS Access prototype
- March 2007
- Production web site available, populated with RAND pilot data and BRN pilot project results