Principles, Organization and Operations of the Veterans Affairs Cooperative Studies Program

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Principles, Organization and Operations of the
Veterans Affairs Cooperative Studies Programs
Biospecimen RepositoriesMary T. Brophy, MD,
MPHDirector, Massachusetts Veterans
Epidemiology Research and Information Centers
(MAVERIC) Core Laboratory
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Overview

• Cooperative Studies Program (CSP)
• Biospecimen banking in CSP
• Study specific banks
• Program specific banks
• CSP DNA Bank
• Veterans Affairs Biorepository Trust (VABT)
• Future Directions

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VA Cooperative Studies Program

• Clinical trial statistical coordinating centers
• Epidemiology research and information centers
• Pharmacy center
• Health economic research center
• Pharmacogenomic laboratory

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Biospecimen Banking in CSP Research

• Rich history of successful research
• Population eager to participate in research
• High quality, large scale clinical datasets
• Well characterized participants
• Longitudinal follow-up for treatment effect
• Integrated medical informatics system

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CSP Study Specific Banks

• Defined sub-studies within the parent study
• Operating procedures were reinvented with each
  study
• Data maintained at CSP coordinating center
• Bank location and standards operating procedures
  varied
• VAMC
• University
• Commercial laboratory
• Oversight and control of access to bank specimens
  was variable
• Issue with longevity

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CSP Program Specific Bank

• MAVERIC core laboratory at the Boston VA
• Established to serve as a central biobank for CSP
  trials
• Clinical data and patient identifiers are
  maintained at the parent trial CSP coordinating
  center
• De-identified samples stored in a state of the
  art biorepository
• Assurance of longevity of bank beyond the parent
  trial

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MAVERIC Core Laboratory

• Developed standard operating procedures for
  biosample collection processing and storage that
  could be used across trial
• Trained sites in sample
• collection and shipping

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Access to MAVERIC Core Laboratory Samples

• Scientific review of proposals to access bank
  specimens are
• Reviewed by PI and executive committee
• Require IRB approval of local investigator
• Oversight is provided by CSP coordinating center
  and the MAVERIC Core Laboratory

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Rationale for a CSP DNA Bank

• Program wide effort to standardize the methods
  for genetic research in CSP trials
• Goals
• To ensure the highest level of human protection
• Maximize the scientific value of the bank
• Lavori et. al. Controlled Clinical Trial
  232222002

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Conceptual Foundation of the DNA Bank

• Oriented toward future hypotheses
• Dynamic and adaptive operational plan
• Scientific and ethical context in genetic
  research is likely to evolve
• Need for broad expertise for planning and
  monitoring
• Need for national standards

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Guiding Principles of the DNA Bank

• Respect for autonomy
• Protection of privacy
• Appropriate disclosure
• Protection from harm to individuals
• Avoid harm to groups
• Deal fairly with commercial interest

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Organization of the CSP DNA Bank

• Coordinating center at CSPCC in Palo Alto
• Administrative
• Clinical data
• Genetic tissue core laboratory at MAVERIC
• Oversight Committees
• Scientific Advisory (SAC)
• Ethical Oversight (EOC)
• Veterans Advisory Group (VAG)

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DNA Bank Standard Operating Procedures
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Access to the DNA Bank

• Statement of research intent
• reviewed by the SAC
• A full proposal is developed
• Reviewed by SAC and EOC
• IBB approval of local investigator
• Material transfer agreement

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MAVERIC Core Laboratory CollectionCSP Clinical
Trials

• CSP Study Population Subjects Specimen
  Type
• 298 HIV 800 P,PBMC
• 363 Hyperlipedemia 2,622 P,DNA
• 387 CAD 1,302 P,BC
• 453 Renal Failure 1,860 P
• 465 Diabetes Mellitus 1,600 P,U,WB
• 512 HIV 285 P,PBMC
• 530 Acute Renal Failure 723 P,S
• 533 Prostate Cancer 18 P,S,N
• P Plasma S Serum DNA Deoxyribonucleic
  Acid U Urine BC Buffy Coats
• WB Whole Blood RC Red Blood Cells N Nail
  clipping
• PBMC Peupheral Blood Mononuclear Cells iRBMC
  Immortalized PBMC
• Separate DNA Bank

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MAVERIC Core Laboratory CollectionCSP Cohort
Studies

• CSP Study Population Subjects Specimen
  Type
• 458 Gulf War 3,263 P,BC
• 499A Healthy Subjects 858 S,BC
• 601 Centenarians 55 P,S,BC
• 710B Normative Aging 3,200 P,S,O,RC,DNA
• 714B Osteoporosis 1,115 P,S,U,DNA
• 719B Prostate Cancer 2,051 P,S,B,C
• P Plasma S Serum DNA Deoxyribonuclemic
  Acid U Urine BC Buffy Coats
• WB Whole Blood RC Red Blood Cells N Nail
  Dippyo PBMC Peupheral Blood Mononuclear Cells
  
• iRBMC Immortalized PBMC

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CSP DNA Bank Collection

• CSP Study Population Subjects
  Specimen Type
• 366A Schizophrenia 925 iPBMC
• 402 Skin CA 325 P,DNA
• 410 CAD 275 P,DNA
• 453A Renal Failure 681 P,DNA
• 478A HIV 2,081 P,DAN
• 481 Warfarin 762 P,DNA,S
• 500A ALS 1,391 P,DNA,S
• 504 Schizophrenia 5 P,DNA
• 519 PTSD 152 P,DNA
• 530A ATN 125 P,DNA
• 533A Prostate Cancer 8 P,DNA,S,N
• P Plasma S Serum DNA Deoxyribonucleic
  Acid U Urine BC Buffy Coats
• WB Whole Blood RC Red Blood Cells N Nail
  Dippyo PBMC Peupheral Blood Mononuclear Cells
• iRBMC Immortalized PBMC

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Rationale for the Veterans Affairs Biorepository
Trust

• Broader source population
• Population based collection
• Diversity of biosamples
• Post operative residual tissue
• Post mortem tissue
• Expanded informational context
• open-ended longitudinal personal health data

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Charitable Trust Model

• Donation of tissue to the bank
• Board of Trustees are stewards not brokers of
  donated tissue
• Donor group advisory role
• Longevity and flexibility
• Winickoff and Winickoff, N Eng J Med
  349(2003)1180.

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Proposed VAB Organization

• Board of Trustees
• Board of Directors
• CSP DNA Bank
• SAC
• EOC
• VAG
• Donor Committee

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VABT Organization

• VABT Coordinating Center
• Administrative Core
• Data Management
• MAVERIC Core Laboratory
• Blood and biologic fluid bank
• Southern Arizona Core Tissue Laboratory at the
  Tucson VA
• Tissue bank

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Access to the VABT

• Statement of research intent
• reviewed by the SAC and Board of Trustees
• A full proposal is developed
• Reviewed by SAC and EOC
• IBB approval of local investigator
• IRB approval of VABT
• Final approval of the Board of Trustees
• Material transfer agreement

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VABT Brain Bank

• Participants from ALS Registry
• Donation of brain and spinal cord
• 63 subject approached
• 19 agreed to participate
• 13 declined
• 5 donations in the bank

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Summary of Current Capabilities

• National full service biorepositories capable of
  storing all types of biological specimens
• Data coordinating centers capable of collecting,
  cleaning, verifying and analyzing large clinical
  datasets
• Ability to adapt to the needs of investigators
  throughout the VA system
• Guidelines for scientific and ethical oversight

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Future Directions

• Technical
• Pharmacogenomic laboratory
• Informational
• Corporate data warehouses that will provide full
  access to all patient health information
• Advanced informatics for storage, retrieval and
  correlation of complex genetic and clinical data
• Governance and Oversight