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Advocacy > The the NCI  Cooperative Group Banks (GCB)

Last update: 08/22/2014


Background | Key Components | Why Now? | News | Ownership Issues | In the News
Ethics of Requiring Tissue Biopsy for Study Participants


"Biospecimens are materials from the human body, such as tissue, blood, plasma, and urine, 
that can be used for cancer diagnosis and analysis." 27

"The number one roadblock to our progress, as defined
at the think tank Dialogues on Cancer (2002), is the lack of availability of high quality, highly characterized 
human specimens for translational research."

The National Biospecimen Network (NBN) has evolved into the Cooperative Group Bank (GCB). The GCB is built on the NCI Cooperative Group System - now called the National Clinical Trials Network (NCTN)

So the acronyms to remember are:

NCTN - the underlying cooperative group system (Alliance, SWOG, etc) that carries out clinical research, and

GCB - the biospecimen bank, consenting, and informatics system that allows for science-driven collaborative research.

Study participant-derived biospecimens stored in the GCB are highly annotated with detailed medical, treatment, and outcome data  - allowing for correlative research .. understanding how the underlying biology of the disease relates to the outcomes in therapeutic trials. 

For example, the information from GCB-based correlative research can help to identify risk factors to guide patient selection in clinical trials ... leading ultimately to more personalized care of patients: "getting the right drug to the right patient at the right dose," avoiding unproductive toxicity, identifying promising treatment targets, knowing when to continue or change treatment ... and more.

In the News:


Important resource:
NCI Cooperative Group (Biospecimen) Banks - CGB http://1.usa.gov/VHMxyD


The Need for Harmonization in Bio-banking to 
Realize the Potential of 21st Century Medicine  Dr. Anna Barker, NCI PDF 


* Medical News Today, 2013:
A roadblock to personalized cancer care? Tumor biomarker tests can help http://bit.ly/1enuWPc

Key components

(1) Standardized collection, storage, and analysis of large numbers of annotated Biospecimens (tissue, blood, urine)  - so that research findings are comparable and the results can be statistically powered

(2) Bio-Informatics software that can store the de-identified clinical and molecular data, linked to the samples.  

(3) Common data elements, so that each research group is reporting and describing data using the same terminology.  

(4) Data sharing, including publishing of failed research, so discovery and validation of biomarkers can be  accelerated and resources can be deployed efficiently. 

(5) Consenting guidelines - including privacy protection - to inspire trust, and ensure participation and  continued public funding.

"Currently there are no standardized procedures for 
collecting, processing, storing, and distributing biospecimens." 27

" Ultimately, it may well be that the optimal treatment will be determined by patient 
clinical and biological characteristics." ~ Dr. Bruce Cheson [4]

Why now?  

FDA ... the vast majority of investigational products that enter clinical trials fail.
Often, product development programs must be abandoned after extensive investment of time
and resources. This high failure rate drives up costs, and developers are forced to use the profits from a decreasing number of successful products to subsidize a growing number of expensive failures. [6] 

Gene expression largely determines how tumor cells behave: how aggressively or slowly they will grow, how resistant they are to dying, how and why they respond to different treatments. 

New technologies, particularly microarrays, can help to characterize gene expression in malignant cells, allowing scientists to see what is wrong, and compare one person's cancer to another's. For the first time in history we can begin to see what we are trying to fix at a fundamental level.  

"The trick with molecular targeting is that you have to be able to match the drug to the patient. And until you understand how the drugs work, why they work, and for whom they work,  your results might not be as remarkable as you would like for them to be.  Once we understand how to match the drug to the patient, I think we will see many, many examples like imatinib [Gleevec]."  
~ Dr. Brian Druker, Howard Hughes Medical Institute [2]

bullet Enable scientist to more rapidly identify the gene mutations or expressions that distinguish normal from malignant cells and assist in the "development of molecularly targeted therapies that have specificity and potency for defined cancer types." [1]
bullet Enable scientists to link clinical behavior (such as how aggressive or indolent the cancer is likely to be) to gene expression, and thus better advise patients about treatment selection and timing. 

The variable clinical course of patients given the same diagnosis stems, in part, from the underlying molecular diversity among their tumors. [1] ~ NBN blueprint 

bullet Help identify viral factors that may be present and may contribute to causing, promoting, or maintaining malignant behavior of lymphoma cells.
bullet Help scientists to discover how genes function in immune cells, and apply this knowledge to the treatment of numerous diseases.
bullet Allow scientists to correlate features in the biology of the disease with individual responses to treatments, in order to:

enable doctors to better match the drug to the patient


spare patients from the side effects of ineffective treatments


identify patients in need of experimental approaches to treatment [3]


reduce health costs by minimizing the trial and error approach to selecting interventions


identify genes in tumors that lead to treatment resistance


select patients most likely to benefit from targeted investigational drugs in clinical trials


Help identify tumor-associated antigens that can form the basis for therapeutic cancer vaccines.

bullet Help discover factors in the microenvironment that may be promoting or inhibiting the disease.

Note that the GCB should not represent a challenge to existing systems that are functioning at high levels. Rather the GCB will incorporate the "best practices" in existing systems of excellence. Identifying, developing, and sharing standards for "best practices" is a process and not an end.  Thus, the GCB will incorporate new ideas and innovations as they occur. It will constantly improve and lead to innovations that will make a real difference. 

" As we move to consider these tumors by their genetic abnormality (genotype) rather than their 
cellular appearance (phenotype), one converts the generalities of leukemia, lymphoma, and 
myeloma into hundreds of diseases with distinct genetic causes, clinical manifestations, 
and drug responsiveness."  29

Briefly, the GCB is a blueprint for creating standards for how to:  


Obtain and store tissue samples suitable for consistent analysis


Apply disease-specific cDNA microarrays in order to measure the expression level of several thousand mRNA, simultaneously in biological tissue, and conduct tests to validate the tools and the procedures


"Screen for genes that are differentially expressed between normal and diseased tissue in order to find novel targets for drug development or to find new single-gene markers of clinical outcome." 10


Protect donor confidentially


Create an open and usable informatics data system, which can provide open access to tissue and data - including longitudinal data (case data followed over time) - thus enabling the correlation of gene profiles with treatment outcomes 

Standards is not a "sexy" word, but adopting standards is the key to releasing the potential of technologies in any age. The Internet was made possible by adopting standards (TCP/IP), as are the infrastructures we all take for granted: electricity, telephone, plumbing, etc.

Shared and open access means small companies can compete as well as large. It shifts the advantage from financial muscle to ideas and creativity. Open access will create productive competition, and capital interest will be sure to follow. Openness will replace the practice of restricting access in order to gain or maintain a commercial advantage - buying up DNA patents, for example. 

* Importantly, the data obtained from tissue is patient DNA. Thus, it should not be "owned" by any group. The NBN blueprint cites this basic fact.

The following is one example of how the GCB approach can foster more rapid approval of new drugs. It should be noted that it's not a futuristic example, as this approach has already been applied to a drug called Herceptin. A drug that would not have won FDA approval without rationally selecting patient populations. This according to GCB background text. And Gleevec is a well-known example of a rationally-developed targeted drug that has made an enormous impact on patients with CML, a type of leukemia. 

Translational or targeted drug development and assessment using NBN resources could go as follows


Standardized collection of biospecimens. 


Find novel targets using microarrays.


Refine diagnosis and identify high- and low-risk disease.


Find clinically useful biomarkers by identify correlations between gene expression profiles and treatment responders. 


Select the appropriate patients for targeted-phase studies.

The result is that smaller studies will be needed to achieve statistically significant results, providing relief from the competition for patients.

Fewer patients will be subjected to the toxicity of drugs that cannot help them. 

The new favorable circumstances causing increased interest in trials and cancer research among patients, investigators, commercial entities ...

Obviously, it will be best if all organizations work cooperatively and support broad adoption and full funding of the GCB. But it will also help if support for the idea is expressed by the patient community

Since, the blueprint is not cancer-specific, the rationale and need should have broad appeal. Since cancer affects almost everyone in the long run, it should have broad support in the general public when they become educated about the potential and the need.  

~ Karl Schwartz 

Is it Ethical to Require a Tissue Biopsy of Participants in Therapeutic Clinical Trials?

See Ethics of Requiring Tissue Biopsy for Study Participants

Additional reading:

Issues Surrounding Biospecimen Collection and Use in Clinical Trials
Allison R. Baer, RN, BSN, Mary Lou Smith, JD, MBA, Deborah Collyar, BS, and Jeffrey Peppercorn, MD, MPH http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2900874/
CFR - Code of Federal Regulations Title 21 - Basic Elements of Consent http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=50.25


Ownership Issues

Based on candid feedback from a prominent lymphoma investigator, local institution “ownership” of extra tissue seems a major challenge to implementing the GCB practices – along with competing research interest, at least at the major centers. 

So who “owns”  or more precisely decides on use of the extra tissue?  The surgeon, the pathology department, the larger institution who owns the storage units, the patient’s treating physician, or the patient?   

It seems that we are too often defaulting to No Use (discarding it), or Unproductive Local Use, because the institutions haven’t thought this through and believe they have ownership rights in these matters.  It seems a legal and ethical question begging for a process to deliberate it.

Related perspectives

* PAL content:
Giving Tissue and Blood
- an advocate's perspective PDF

"Consent" for unspecified future use?  PAL



  1. The NBN blueprint document: (~226 pages)  PDF  
    (It may take some time for this large document to appear in your browser.)  
  2. Molecular Targeting in the Treatment of Cancer: An Interview With Brian Druker, MD  Medscape (free login req.)  Related commentary: See the National Biospecimen Network 
  3. Staudt, Gene Expression Profiling of Lymphoid Malignancies -  Annu.Rev.Med.2002.53:303–18  PubMed
  4. Advances in the Treatment of Non-Hodgkin's Lymphoma - Dr. Cheson  Medscape (free login)
  5. Innovation or Stagnation? Challenge and Opportunity on  the Critical Path to New Medical Products PDF 2004 FDA 2004
  6. Molecular Diagnostics  Rita M. Braziel, Margaret A. Shipp, Andrew L. Feldman, Virginia Espina, Mary Winters, Elaine S. Jaffe, Emanuel F. Petricoin III and Lance A. Liotta  asheducationbook.org
  7. Primer on Medical Genomics Part III: Microarray Experiments and Data Analysis
    Ayalew Tefferi, et al. Mayo Clin Proc. 2002;77:927-940  PDF 
  8. Clinical Application of cDNA Microarrays in Oncology ~ Full text  theoncologist.alphamedpress.org/
  9. Gene expression profiling in Follicular Lymphoma to assess clinical aggressiveness and to guide the choice of treatment. Blood. 2004 Sep 2 PMID: 15345589 | Related abstracts
  10. [2266] Follicular Lymphoma: Design of a Protein-Based Survival Predictor Using Tissue-Microarrays (TMA). Session Type: Poster Session 479-II  ASH 2004
  11. [1125] Gene Expression Profiling Analysis in Splenic Marginal Zone Lymphoma Allows To Predict Survival and Histological Transformation. Session Type: Poster Session 279-I  ASH 2004
  12. Scientists Unlocking Lymphoma's Secrets - The microenvironment   accessatlanta 
    "Genetic differences -- not in lymphoma cells, but in immune cells surrounding the tumor -- may determine how aggressive a particular case of follicular lymphoma turns out to be"
  13. Molecular Diagnostics on Lymphoid Malignancies ~ Wing C. Chan, MD; Kai Fu, MD, PhD  allenpress.com
  14. Study Demonstrates Gene Expression Microarrays Are Comparable And Reproducible  sciencedaily.com
    "A study funded by the National Cancer Institute, part of the National Institutes of Health, shows for the first time that microarray data generated in different laboratories can produce highly comparable results. For this comparison study, appearing in the Jan. 15, 2005, Clinical Cancer Research*, four separate laboratories analyzed gene expression (whether genes are turned on or off) for the same set of human tumor tissues. Overall, the expression profiles of portions of individual samples were highly comparable, and the experimental correlation between separate labs was only slightly lower than correlation of duplicated experiments within the same labs."
  15. Researchers Use Novel Technology To Extract RNA From Archive 
    Formalin-fixed Paraffin-embedded Tissue  sciencedaily.com 
    "Recent advances in both laser-capture microdissection (LCM) technology and microarray technology have revolutionized our investigation of the genetic basis of human cancer," ... "Pure cell populations can now be isolated ... and evaluated for changes in gene expression that accompany the development of cancer. However, applying these techniques to archived clinical specimens has been limited by our inability to extract high-quality genetic material from routinely processed clinical samples."
  16. How patients can help accelerate advanced tissue-based research  http://biospecimens.cancer.gov/ 
  17. Improving Diagnosis and Treatment of Lymphomas with Gene Expression Profiling   hematology.org 
    Joseph M. Connors, M.D.
    "Major new insights into the biology of lymphomas have resulted from the use of microarray gene expression technology to elucidate their underlying biology and to identify novel pathways for therapeutic intervention."
  18. Biobank Central  biobankcentral.org  

    BioBank Central aims to describe the activities of modern biobanks in all their breadth, ranging from the absolute requirement to protect the interests of patients and healthy volunteers who choose to donate samples and data, to the critical role of these biorepositories in enabling modern biomedical research.
  19. caBIG: Power of Connection™ - Dr. Barker provides a preview.   cabig.cancer.gov
    The video explores the challenges of cancer research and how caBIG™ 
    will speed research discoveries and improve patient outcomes by connecting 
    the cancer community.
    Also see Glossary: http://cabig.cancer.gov/resources/glossary.asp
  20. caIMAGE: Enabling Standardization and Collaboration  cabig.cancer.gov 

    Greater reliance on imaging in clinical care and biomedical research, the current structure of clinical studies, and other advances in technology have led to an enormous increase in the quantity and complexity of cancer imaging data. Despite this increase, however, there is little standardization of protocols used to acquire, analyze, and annotate images among cancer centers and other research facilities.
  21. GenePattern - Integrated Genomics - now a part of caBIG  cabig.cancer.gov 

    One feature unique to GenePattern is the ability to track the different steps that a researcher takes when analyzing a set of data. These computational and research steps, known as a “pipeline,” are stored along with their parameters on the GenePattern server. Researchers with access to the dataset can request that the same analytical steps, or “pipeline,” be repeated and/or combined with other pipelines. Reproducibility, an essential feature of many successful research projects, can be easily accomplished using GenePattern. Also, the ability to string together pipelines opens the door to new discoveries by enabling the exploration of increasingly complex hypotheses.
  22. The Office of Biorepositories  NCI 
  23. Modernizing Cancer Research  PAL PDF 
  24. Biospecimen Basics  http://biospecimens.cancer.gov/global/pdfs/BiospecimenBasics.pdf 
  25. NCI Best Practices (2007) http://biospecimens.cancer.gov/global/pdfs/NCI_Best_Practices_060507.pdf 
  26. Biospecimens: Challenges and Solutions in Clinical Cancer Research  www.calgb.org/Public/publications/calgabs/2006/winter2006.pdf 
  27. Tissue preparation (devil in the details)  www.nature.com

    According to experts, there are more than a billion tissue samples archived in hospitals and tissue banks around the world, most of them formalin-fixed and paraffin-embedded (FFPE). Today, these samples present both an incredible opportunity and a huge challenge to researchers. FFPE tissue samples have been extensively annotated and well preserved, allowing detailed study of the progression of diseases such as cancer. But due to the method of preservation, obtaining biomolecules from these samples is proving difficult, to say the least.
  28. Biobanking of fresh frozen tissue: RNA is stable in nonfixed surgical specimens www.nature.com | PDF

    Our data indicate that nonfixed tissue specimens may be transported on ice for hours without any major influence on RNA quality and expression of the selected genes. However, further studies are warranted to clarify the impact of transport logistics on global gene expression.
  29. Battling the Hematological Malignancies: The 200 Years' War

    Full article  http://theoncologist.alphamedpress.org/cgi/content/full/13/2/126 
  30. Gene expression signatures in follicular lymphoma: are they ready for the clinic?  http://haematologica.org/cgi/content/full/93/7/982 
  31. The Biology of Human Lymphoid Malignancies Revealed by Gene Expression Profiling
    Louis M. Staudt and Sandeep Dave http://www.pubmedcentral.nih.gov (full text)


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For all medical concerns,  you should always consult your doctor. 
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