"Banking and Disbursement of Tissue and other biologic materials".
IRB submission by the Health Sciences Tissue Bank, University of Pittsburgh
and the University of Pittsburgh Health Systems.
1.0 Specific Aims
The overall aim of the Health Sciences Tissue Bank (HSTB), University of
Pittsburgh and the University of Pittsburgh Health Systems, is to serve as a one-source
provider of tissues for educational and research purposes. Collecting and banking
normal, inflamed, malignant, and metastatic tissue from patients with a variety of diseases
would accomplish this.
The research material resource resulting from the collection of these tissues and
biological specimens is intended to provide research resources for investigators. This
will allow the researchers to pursue individual research initiatives. The HSTB is meant
primarily for investigators inside the University of Pittsburgh, the University of
Pittsburgh Medical Center, and the University of Pittsburgh Cancer Institute. However
collaborative relationships are permissible, as long as appropriate institutional
approval, standard Material Transfer Agreements and Sponsored Research
Agreements (where applicable) are in place.
2.0 Background and Significance
The use of human tissues is an essential requirement for many experimental and
research protocols to help develop a better understanding of disease. This is imperative
to improve our current diagnostic and therapeutic modalities.
The HSTB serves to provide a broad-based supply of biological materials for
research purposes. These include tissue, blood, urine, other biological materials and
clinical information that would otherwise require many years to assemble based on
research-ready protocols. The Tissue Bank would encourage the rapid dissemination of
research and results, thus providing a higher visibility for the institution as well as
arriving at much needed answers in the various fields of research.
3.0 IRB workflow; guidance from the OHRP
The HSTB is IRB approved for collecting excess tissue and biological materials
Introduction
The Federal Policy defines “human subject” research as a process where an
investigator conducting research obtains (1) data through intervention or interaction with
the individual; or (2) identifiable private information.” As per the new guidance from the
OHRP (August 10, 2004), research activity involving "de-identified" specimens and data
would not be considered as research involving human subjects and would not need
specific IRB approval.
This revised definition of human research impacts the functioning of the HSTB.
The HSTB has in place the appropriate infrastructure, software tools and IRB approvals
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to handle collection of tissue and biological materials as well as their de-identified
disbursement. The HSTB is an IRB certified "Honest Broker" facility.
Rationale
The majority of requests to the tissue resource are for biological materials, and
annotating data, to be utilized for research purposes. The investigators do not need any
identifiable information in almost all instances.
The HSTB is IRB approved for collecting excess tissue and biological materials.
In addition, the HSTB is a certified honest broker facility (HB 015). This honest broker
certification was part of a larger, more comprehensive, submission, incorporating the
HSTB, the Cancer Registry, the oncology groups (medical oncology and radiation
oncology), the Outcomes group, and Pathology and Oncology informatics. This honest
broker entity essentially covers all aspects of biological specimen and data needs for
researchers.
The combined capabilities of the HSTB and this honest broker facility should be
able to address almost all needs of researchers, in a manner compliant with current legal
and ethical considerations, consistent with current OHRP recommendations.
4.0 Banking Methods
Current process for aggregation of research biological materials and annotating
data
The HSTB procures excess materials for research purposes. This aggregation is
performed after adequate materials have been obtained for diagnostic purposes. These
research tissues are provided to investigators only after clinical diagnostic issues have
been accomplished (report signed out on that specimen).
This research material procured is from two different sets of tissue samples:
1.
Consented patients: These patients are approached for tissue donation for
research purposes in their doctor's offices. The consent form used maybe
generic or designed for the specific program. The specimens from consented
patients are stored using a linkage code that allows subsequent additional data
aggregation. We also utilize a bar coding system. This further addresses
issues pertaining to patient confidentiality and identification of specimens.
2.
Excess tissue specimens from patients not specifically consented for
research tissue aggregation: These patients have not been approached for
consent. The excess tissue specimens are initially collected and stored for
potential clinical purposes, in case additional tissue sections might need to be
evaluated for diagnostic purposes. These specimens are moved to the HSTB
research repository once the clinical sign-out is accomplished. Since these
patients have not been consented, these specimens are annotated only with the
surgical pathology report. The annotating surgical pathology report contains
de-identified (HIPAA compliant) data. This annotating report does not
contain the surgical pathology number or any other mechanism to identify the
patient. No additional data aggregation is permissible for these specimens.
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3.
Mechanism for dealing with refused consent: Rarely a patient refuses when
approached for consent for research tissue and biological specimen
aggregation. The doctor's offices communicate this back to the HSTB. No
residual biological material is collected for research purposes from these
patients.
There might be instances where information regarding refusal of consent is not
communicated from the doctor's offices to the HSTB. This is recognized as a potential
problem. However research samples that do not have a consent form are anonymized.
The identity of the patient would therefore be removed from the sample.
We are working for software solutions to this problem. This would consist of creating a
mandatory data field regarding consenting that would need to be appropriately filled in
during patient registration. The IRB will be informed of future progress and
developments.
Disbursement of tissue specimens for research
All specimens are disbursed in a de-identified fashion. The honest broker
functionality of the HSTB is extensively utilized to provide investigators with needed
tissue and biological specimens, and annotating data, in a completely de-identified
fashion. The HSTB uses linkage codes and stores the key to these codes on password
protected, computers, within the secure protective firewall of the University of Pittsburgh.
No tissue and biological specimens, and annotating data, are ever provided with
identifiers.
Current functioning of the HSTB
Electronic tools: The HSTB has electronic tools for storing information pertaining to
these specimens. The HSTB uses a bar coding system, which eliminates use of any
identifiable information for labeling research specimens. The HSTB also uses
institutional tools, like MARS. There is also access to additional electronic tools
developed for the Cancer Registry and for the HSTB. These tools facilitate the deidentification of specimens being disbursed for research. In addition the same toolset can
be utilized for the de-identifying data for research.
Administrative infrastructure and oversight: As part of institutional infrastructure, the
HSTB has constituted "Tissue Utilization Committees" (TUC) in various important areas
of research. The TUCs comprise the group of prominent individuals in that particular
organ type area (oncologist, surgeon, researcher, and pathologist). The TUC approves of
requests for research materials in that specific area.
There is an institutional oversight committee that supersedes the TUC. The
institutional oversight committee consists of the top hierarchy of the University of
Pittsburgh. This institutional oversight committee currently consists of the Director of
UPCI (Dr. Nancy Davis), the Chairperson of Pathology (Dr. George Michalopoulos), the
chairperson of Thoracic Surgery (Dr. James Luketich) and the Chairperson of the
Department of Biomedical Informatics (Dr. Michael Becich). The director of the HSTB
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serves as a member and executor of the decisions of this institutional oversight
committee.
The above description is of the system currently in place. This system has been
implemented and is fully functional.
Workflow
The implementation of the above mechanisms for tissue and data aggregation, deidentification and disbursement of de-identified tissue specimens provides an opportunity
for streamlining workflow for the HSTB as well as for the IRB committee.
1.
2.
3.
4.
5.
Researchers should submit their tissue and biological specimen requirements,
as well as data needs, directly to the HSTB. This would apply only to
instances where no identifiable information is needed.
The HSTB would direct the application to the TUC for approval.
If approved, the HSTB would provide appropriate biological specimens, and
annotating data, in a de-identified manner to the investigators.
The investigators would need to enter into an agreement by which they
guarantee that no additional data mining will be attempted, without additional
approval. In addition the researchers cannot share these materials with other
investigators, as well as outside institutions, without additional approval. This
agreement is attached with this IRB submission.
The HSTB will keep track of all of these requests. The HSTB will provide an
annual report to the IRB of specimen utilization, at the time of annual renewal.
This report will contain a summary of every request processed under the IRB
0506140. The IRB will also be immediately apprised of any other
unanticipated problems or issues that might arise as part of implementation of
this system.
This workflow modification applies only to current existing specimens, as well as new
accruals collected as part of “random excess aggregation of tissue specimens”.
The following scenarios would need specific IRB approval:
1.
Specific prospective focused (non-random) excess tissue collections.
2.
Collection of specimens only for research, without clinical evaluation.
Collection of specimens in (1) is an extension of the existing capabilities of the
facility. However the collection would be non-random, since there is a specific purpose
and research driver.
Collection of specimens in (2) is only for research purposes and not for clinical
purposes. The entire specimen goes to the research repository, without any clinical
diagnostic evaluation. The patient needs to be aware of this and provide informed
consent.
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The HSTB combines its honest broker facility, and the tissue and biological
specimen collection capabilities, incorporating the OHRP guidance; and create a
procedure for tissue and biological specimen, and annotating data, disbursement. This
workflow would significantly streamline triaging tissue and biological specimens for
research purposes.
5.0 Use of Tissue Bank Samples for Research Studies
The HSTB will provide tissues for research purposes to researchers for different
research protocols. The tissues provided for these research protocols would be procured
and stored in the HSTB using the methodologies discussed above. The methodologies
of providing the tissues to the researchers are as follows:
1.
2.
Anonymized provision of samples: Banked samples (non-identifiable or
identifiable) may be provided to researchers without any subject identifiers
or linkage codes. The tissues provided would thus be completely
anonymized. The samples will be accompanied only by the Pathology
report, which will be completely anonymized.
“Honest broker” provision of samples: Banked identifiable samples and
the corresponding Pathology reports may be completely anonymized, but
assigned a unique code number by the HSTB, prior to providing the
samples to researchers. This unique code number will permit the
researchers to obtain additional information about the sample or additional
sample specimens; however the HSTB (i.e. the Honest Broker) will retain
information linking the unique code number with the subject’s identity.
With either of the above methodologies, the samples will be provided to the
researchers in such a manner whereby the subjects cannot be identified (by the
researchers) directly or indirectly through identifiers linked to the subjects. Hence
the researchers would not be required to re-obtain informed consents from the
patients whose tissue and biological materials have been banked for research (Sec
45 CFR 46.101 (b) (4).
6.0 Human Subjects
The racial, gender, age, and ethnic characteristics of the proposed subject
population reflect the demographics of Pittsburgh and the surrounding area and/or the
patient population of the University of Pittsburgh Medical Center. No exclusion criteria
shall be based on race, ethnicity, gender, age, or HIV status.
The offices of the physicians providing clinical care will approach patients for
obtaining informed consent. In addition there will be a nurse coordinator/ physician
assistant/ Tissue Bank staff person who will approach patients for consent prior to surgery
or performance of the procedure that will make the tissues available. Attempts will be
made to involve as many clinical caregivers as possible in the process of consenting.
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The actual risks to patient, as well as the researchers and technical support they
employ, is negligible. Precautions in processing tissue, blood, and urine samples are taken
according to hospital, OSHA, and federal regulations, and no additional risk is expected.
7.0 Costs and Payments
The patient subject shall incur no costs for inclusion of his/ her tissue or
biological material in the Tissue Bank outside of what would normally be incurred as a
part of his/her medical treatment. Similarly, the patient/ subject will receive no
remuneration for the inclusion of his/ her tissue or biological material in the Tissue Bank.
Tissue Bank personnel and the Tissue Bank itself support the activities related to the
processing, banking, and disbursement of research materials.
8.0 Data and Safety Monitoring Plan
Summary of Research Study:
Tissue materials will be obtained from surgical pathology specimens after clinical
evaluation. These residual specimens will be stored by the Tissue Bank of the Department
of Pathology. The tissue bank will file the specimens, and associated information, using
appropriate safeguards to ensure confidentiality.
Data and Safety Monitoring Plan:
1.
2.
The data is stored on password-protected computers.
The data is provided to investigators only after the identifiers have been removed.
The data is NEVER provided with any identifiers. A linkage code is used. The
Tissue Bank retains the key to the code.
3.
The PI evaluates the data every quarter to assess the volume of accrual and the
variety of specimens accrued.
No adverse effects are expected from this study.
4.
9.0 PRINCIPAL INVESTIGATOR
Rajiv Dhir, MD
Associate Professor and Staff Pathologist
Director, Health Sciences Tissue Bank,
University of Pittsburgh and University of Pittsburgh Health Systems
UPMC Shadyside-Presbyterian Hospital
5230 Center Avenue, Room WG 07
Pittsburgh PA 15232
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E-mail: dhirr@msx.upmc.edu
Phone: (412) 623-1321
Beeper: (412) 765-8600
Fax: 412-682-6450
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