Applying catissue to the biospecimen quality problem
Download
1 / 18

Applying caTissue to the Biospecimen Quality Problem - PowerPoint PPT Presentation


  • 161 Views
  • Uploaded on

Applying caTissue to the Biospecimen Quality Problem. Carolyn C. Compton, M.D., Ph.D. Director, Office of Biorepositories and Biospecimen Research Acting Director, Office of Technology and Industrial Relations caBIG Annual Meeting 2008 Washington, DC.

loader
I am the owner, or an agent authorized to act on behalf of the owner, of the copyrighted work described.
capcha
Download Presentation

PowerPoint Slideshow about ' Applying caTissue to the Biospecimen Quality Problem' - maurilio-nihill


An Image/Link below is provided (as is) to download presentation

Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.


- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -
Presentation Transcript
Applying catissue to the biospecimen quality problem

Applying caTissue to the Biospecimen Quality Problem

Carolyn C. Compton, M.D., Ph.D.

Director, Office of Biorepositories and Biospecimen Research

Acting Director, Office of Technology and Industrial Relations

caBIG Annual Meeting 2008

Washington, DC


Progress in cancer treatment and research are dependent on high quality human biospecimens

Genomics Proteomics Metabolomics

Progress in Cancer Treatment and Research are Dependent on High Quality Human Biospecimens

Identification of targets for drug development, treatment and prevention

Identify biologic variations that determine drug efficacy and drug toxicity

Defining markers for susceptibility, screening and reoccurrence

Development of molecular based taxonomy of cancer

Elucidation of molecular mechanisms of neoplasia

Validation of new therapeutics

All DependOn High-Quality, AnnotatedHuman Biospecimens


Biospecimens have their own unique biologic and molecular life history
Biospecimens Have Their Own Unique Biologic (and Molecular) Life History

  • Life history: parts I, II and III

    • Associated with the clinical history of the patient while in situ

    • Apart from the patient after removal until stabilization

    • Post-stabilization degradation

  • All influence the molecular profile of the specimen

    • What is the influence of each “part” of the continuum on a given molecular profile?

  • How can we tell biologic fact from biologic artifact?


The recorded life history of a biospecimen a story in progress

Medical/ Life History

Surgical

Procedures

Restocking

Unused

Sample

Handling/

Processing

Scientific

Analysis

Patient

Acquisition

Storage

Distribution

The Recorded Life History of a Biospecimen: A Story in Progress

Compilation and Analysis of

Biospecimen Information

Compilation and Analysis of

Scientific Data

Clinical/Clinical Research Outcomes


Annotated Variables are Key Pieces to the Puzzle: Which Elements of a Molecular Profile Reflect the Biology of the Disease vs. Artifact

Post-acquisition:

  • SOPs for specimen processing?

  • Preservation and processing variables?

  • Storage and shipping conditions?

  • QA/QC measures for specimen processing methods and reagents used?

  • Key Data:

  • Pre-acquisition:

    • Pre-op treatments administered?

    • Intra-op drugs delivered?

    • Intra-operative events (bleeding; blood pressure changes)?

    • Surgical variables (duration; approaches; modifications)?


Variables surrounding biospecimen acquisition
Variables Surrounding Biospecimen Acquisition Elements of a Molecular Profile Reflect the Biology of the Disease vs. Artifact

  • 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

Post-acquisition variables:

  • Time at room temperature

  • Temperature of room

  • Type of fixative

  • Time in fixative

  • Rate of freezing

  • Size of aliquots

  • Type of collection container

  • Biomolecule extraction method

  • Storage temperature

  • Storage duration

  • Storage in vacuum


Framework for understanding the impact of variables on molecular analysis
Framework for Understanding the Impact of Variables on Molecular Analysis

VARIABLES

OTHER TECHNOLOGIES

CGH

CGH

CGH

CGH

CGH

CGH

CGH

CGH

Analysis Method

FISH

FISH

FISH

FISH

FISH

FISH

FISH

FISH

PCR

PCR

PCR

PCR

PCR

PCR

PCR

PCR

  • NORTHERN

DNA

PCR

  • RT-PCR

WESTERN

MICRO-ARRAY

Feature of Interest

RNA

  • MASS SPEC

  • SCANNING EM

PROTEIN

IMMUNOSTAINING

  • TRANSMISSION EM

LIGHT MICROSCOPY (H&E)

MORPHOLOGY

Blood

Serum

Plasma

Urine

Saliva

Normal

Tissue

Cancer

Tissue

Other

Specimen Type


Pre and post acquisition variables impact clinical and research outcomes
Pre- and Post- Acquisition Variables Impact Clinical and Research Outcomes

  • Effects on Clinical Outcomes

    • Potential for incorrect diagnosis

      • Morphological/immunostaining artifact

      • Skewed clinical chemistry results

    • Potential for incorrect treatment

      • Therapy linked to a diagnostic test on a biospecimen (e.g., HER2 in breast cancer)

  • Effects on Research Outcomes

    • Irreproducible results

      • Variations in gene expression data

      • Variations in post-translational modification data

    • Misinterpretation of artifacts as biomarkers


Biospecimen Research Network (BRN): Defining the influence of pre-and post-acquisition variables on downstream molecular analysis data

BRN research addresses the following challenges in biospecimen science:

  • Bridging gaps between existing clinical practice and emerging technologies

  • Defining significant variables for prospective collections

  • Developing evidence-based SOPs and biospecimen quality indicators

    Activities of the BRN program to date:

  • Public outreach to define issues and needs in biospecimen standardization

  • Consulting on biospecimen issues for programs within NCI/NIH

  • BRN laboratory: research studies with intramural and extramural collaborators

  • Development of the Biospecimen Research Database

    • Searchable web tool for biospecimen literature/published data

  • Extramural research programs to define pre-analytical variables


New extramural research program
New Extramural Research Program of pre-and post-acquisition variables on downstream molecular analysis data

An ordered approach to filling the knowledge gaps: RFP

  • Studies designed to assess effects of pre-analytical variables in human specimens on the results of genomic, epigenomic, and proteomic analyses

  • Model of variable-controlled and/or variable-annotated biospecimen acquisition and invariable molecular analysis

  • Trans-disciplinary and highly collaborative design

    • Addresses the many operational factors that influence specimen variation

      A creative approach to meeting existing challenges: BAA

  • Solicitation of solutions to unmet needs and difficult issues


Tissue acquisition and processing variables
Tissue Acquisition and Processing Variables of pre-and post-acquisition variables on downstream molecular analysis data

  • Post-operative ischemia

  • Room temperature

  • Type of preservative

  • Rate of freezing/fixing

  • Tissue processing

  • Multiple formulaic variables

  • - Multiple time settings for each

  • Recorded/annotated

  • Anesthesia

  • Intra-operative ischemia

  • Many other variables

Four hospital centers

Cancer and normal tissues

Yrs 1-2: Assess existing variables, compare among sites, same sample types

Years 3-5: Systematically alter selected variables, intra-specimen comparisons

H&E

IHC

FISH

RNA isolation

Storage




Biospecimen research case studies annotation of blood collection and plasma processing variables
Biospecimen Research Case Studies: Annotation of Blood Collection and Plasma Processing Variables



Pathway to scientifically validated specimen handling practices
Pathway to Scientifically Validated Specimen Handling Practices

Data-Driven

Quality SOPs

Biospecimen Research

Empirical

NCI Best Practices for Biospecimen Resources

2007

Restocking

Unused

Sample

Medical/

Surgical

Procedures

Handling/

Processing

Storage

Distribution

QC/QA

Acquisition


Expected program outcomes
Expected Program Outcomes Practices

  • Publications and presentationsfrom the program on the effect of human specimen pre- and post-acquisition variables on downstream molecular analysis

  • Publicationsfrom members of the scientific community at large in response to raised awareness of the importance of such studies

  • Increased attention to QA/QC important to downstream molecular analysisby manufacturersof consumables, reagents, and robotics (e.g., vacutainers used for blood collection, tissue preservatives, tissue processors)

  • CAP guidelines based on new data with implementation in the clinical arena: Greater attention to QA/QC of hospital tissue preservation procedures and equipment, resulting in higher quality preserved tissues for patient molecular diagnosis and research

  • Implementation of data-driven standards for specimen handling in new venues: Inclusion of biospecimen handling parameters in clinical trials and in research, development, and regulation of cancer biomarkers

  • GREATER REPRODUCIBILITY OF RESEARCH AND CLINICAL RESULTS


Applying catissue to the biospecimen quality problem1

Applying caTissue to the Biospecimen Quality Problem Practices

Carolyn C. Compton, M.D., Ph.D.

Director, Office of Biorepositories and Biospecimen Research

Acting Director, Office of Technology and Industrial Relations

caBIG Annual Meeting 2008

Washington, DC


ad