Appendix N Nonprofit, Government-Funded Example: The Cooperative Human Tissue Network * The Cooperative Human Tissue Network (CHTN) provides biomedical researchers with access to human tissues. Six member institutions coordinate the collection and distribution of tissues across the United States and Canada in six regional divisions. The CHTN specializes in the prospective procurement, preservation, and distribution of human tissues for research. In addition to normal, benign, and malignant tissues, tissues from patients with specific diseases such as ulcerative colitis, a premalignant state, are provided. Trained personnel coordinate the retrieval, preservation, and delivery of specimens obtained from surgical resections and from autopsies. Regional Divisions The CHTN has six regional divisions: The Eastern Division is responsible for the area of the Northeast bounded by the western and southern borders of Pennsylvania, as well as Delaware, Alaska, and Hawaii. The Mid-Atlantic Division is responsible for Maryland, Virginia, and the District of Columbia. The Midwestern Division includes West Virginia and states west of Pennsylvania, north to Minnesota and south through Missouri, as well as Canada. The Southern Division encompasses Kentucky and all states south and west from the Carolinas to Texas. The Western Division covers all states north of Oklahoma and west of Texas. The Pediatric Division provides childhood tumors and diseased and normal tissues nationwide. Tissue Processing and Storage The processing of specimens varies according to the protocol of each individual investigator. Specimens can be snap-frozen and stored for limited periods of time at ultralow temperatures, according to the investigator’s needs. Alternatively, investigators may require fresh tissues that can be collected using an aseptic technique, if necessary. Fresh tissues can be minced, placed in transfer media, and shipped to investigators for next-day arrival. Similarly, for research involving substances stable after fixation, fixed or paraffin-processed tissues can be provided. In addition, some divisions offer limited histological processing by special arrangement. This includes hematoxylin-and-eosin-stained sections and stained or unstained frozen sections. The institutions and Principal Investigators comprising the CHTN make every effort to ensure that there is an equitable distribution of tissues into and by the CHTN. In addition, several factors act to prevent CHTN tissue resources from benefiting only a limited number of investigators. Foremost, except for rare tumors, the number of surgical specimens is usually adequate for the recovery of research material. Investigator Costs To Use Resources Investigators pay a nominal processing fee for specimens received from the CHTN: $20 per sample for researchers at academic institutions and $60 per sample for researchers at nonacademic institutions. Slides and blocks accompanying tissue samples may be available at costs ranging from $4.50 to $8.50. The charges are not for the tissues, but to partially offset the costs of collecting, handling, and preparing the specimens in accordance with the detailed requirements of the investigators. Investigators must also pay the cost of shipping specimens to their laboratory. Access Requirements and Priority Access to the CHTN is provided to any investigator who signs the agreements regarding biohazards and commercial use and who provides a summary of the project for which the tissues are requested. Patient identity or other identifying information cannot be provided to investigators. This ensures complete confidentiality regarding medical information of patients. In addition, a copy of the approval of the research, which is obtained from the investigator’s local institutional review board (IRB) for human use, is required for all projects. Canada is the only foreign country for which tissues are provided to investigators (via the Midwestern Division). Requests from other countries will not be filled. The CHTN seeks to provide tissues to the widest group of investigators practicable, and tissues are not restricted to investigators with National Institutes of Health (NIH) grants. In this regard, no investigator should expect to have access to unlimited numbers of malignant specimens of one type. If a large number of specimens and/or extensive patient data are required, it may be necessary to contact the National Cancer Institute (NCI) Tissue Expediter, consult the NCI Specimen Resource Locator, or identify local sources for the specimens and data. The CHTN attempts to provide each investigator with as many specimens as is equitable. Investigator access to increased numbers of specimens is improved by requesting as small a specimen as possible. For example, investigators requesting a minimum of 10 grams of one tumor would have access to only a very limited number of specimens, while investigators requesting a minimum of 0.5 grams of tumor would have access to many more samples. Access to specimens varies according to the surgical schedules and autopsy rates; thus, access is not predictable. Therefore, investigators requesting fresh specimens should make every effort to use these specimens when they are made available. Investigators may be charged a processing fee for specimens collected according to their protocol that are subsequently refused. Coordinating Committee The experience of personnel from all divisions of the CHTN is utilized in a coordinating committee that formulates policies for the operation of the CHTN. Voting members of this committee include the Principal Investigator and an additional member from each of the six divisions. In addition, NCI has one voting member. The coordinating committee meets periodically to assess the operation of the CHTN and to change or modify operating policies. A chairman and secretary of the committee are elected yearly. History of the Cooperative Human Tissue Network The CHTN was formed in 1987 by three organizations, along with a subcontract with the Children’s Cancer Group. In 1991, the Pediatric Division became an independent group, and an additional adult collection center was added to the CHTN. The following six organizations, which currently comprise the CHTN, have extensive experience in providing human tissues for research: Ohio State University has had an internal tissue procurement service, sponsored by the Ohio State University Comprehensive Cancer Center, since 1975. In 1987, it joined the CHTN. Daniel Sedmak, M.D., is the Principal Investigator for this Midwestern Division of the CHTN. The Pediatric Division, located at Children’s Hospital of Columbus, under the direction of Stephen J. Qualman, M.D., obtains most of its specimens through Children’s Oncology Group institutions. The University of Alabama at Birmingham’s Tissue Procurement Facility has supplied fresh and snap-frozen human tissues to investigators within and outside of their Comprehensive Cancer Center since 1978. The University of Alabama at Birmingham joined the CHTN in 1987. William E. Grizzle, M.D., Ph.D., the Principal Investigator for this Southern Division of the CHTN, is a board-certified clinical and anatomic pathologist as well as a funded medical researcher. The University of Pennsylvania serves as the Eastern Division of the CHTN, under the direction of Principal Investigator, Dr. Virginia LiVolsi, Professor of Pathology and Laboratory Medicine, who has served as the Eastern Division Principal Investigator since the inception of the CHTN. During that time, the Eastern Division has expanded its tissue procurement network to include numerous hospitals in the Eastern region. The University of Virginia has had a tissue procurement service since 1993. It served NCI as a major tissue supplier for the Cancer Genome Anatomy Project. Dr. Christopher Moskaluk, Assistant Professor of Pathology, serves as the Principal Investigator of the Mid-Atlantic Division. Vanderbilt University had a Tissue Procurement Facility that operated as a subcontract tissue procurement site for the CHTN for 6 years before becoming the Western Division of the CHTN in 2001. Dr. Mary Kay Washington, Professor of Pathology, is currently the Principal Investigator of the Western Division. Specimen Types The CHTN obtains tissues from routine surgical resections and autopsies. In addition, remnant body fluids (e.g., serum, leukapheresis products, pleural effusions) are available on some patients, and limited histological services (e.g., frozen sections) can be obtained by special arrangement. Normal tissues (i.e., microscopically uninvolved by disease) commonly available from surgical resections include skeletal muscle, skin, bone, cartilage, connective tissue, breast, adipose tissue, small and large intestine, arteries, veins, thyroid, lung, gynecological tissues, kidney, spleen, tonsils, testes, salivary glands, and oral mucosa. Various pathological tissues also are obtained from surgical resections, including head and neck malignancies and carcinomas of the lung, gastrointestinal tract, breast, genitourinary system, prostate, kidney, and skin. In addition to the above more common specimens that are provided to investigators from surgical resections on a regional basis, access to rare tumors, e.g., neuroendocrine tumors and sarcomas, is provided from all divisions via networking. Pediatric tumors and diseased and normal tissues are available nationwide. Additional normal tissues can be obtained from autopsies. These include liver, pancreas, adrenals, brain, pituitary, lymph nodes, heart, and thymus. Quality Control All specimens are subject to an immediate gross examination by a pathologist. The diagnosis then is verified through frozen section, touch preparations, or subsequent evaluation of permanent histopathology. In most cases, the diagnosis can be assured before the specimen is released to the investigators. However, in some cases in which fresh specimens are needed, the tissues are provided to the investigators with a preliminary diagnosis, and the investigators are informed of the final diagnosis as soon as this information is available. In all divisions and institutions affiliated with the CHTN, pathological diagnosis and patient care have priority over the use of any specimen in research. CHTN Policy for IRB Approval The CHTN requires researchers to (1) agree to follow the provisions of the “Common Rule” (45CFR46) Federal human subjects regulations and (2) obtain IRB approval before receiving specimens for their research. While these regulations currently do not apply to institutions that do not receive Federal support, the CHTN policy requires all researchers using CHTN tissues to follow the Common Rule. The CHTN does not provide patient identity or other identifiers to investigators. This ensures complete confidentiality regarding patients’ medical information. Commercial Use of CHTN Tissues Tissues are provided by the CHTN only for research purposes. Before requests are accepted by the CHTN, investigators must sign a statement that they “shall not sell any portion of the tissues provided by the CHTN, or products directly extracted from these tissues (e.g., protein, mRNA, or DNA).” The recipients also must agree that they shall not transfer tissues (or any portion thereof) supplied by the CHTN to third parties without prior written permission from the CHTN. The intent of the CHTN is to encourage research using human tissues for the good of the public rather than for private gain. The commercial development of products from tissues could raise questions of ownership for patentability of products so developed. Disputes over ownership and royalties could disrupt significantly the ability of the CHTN to distribute tissues based on scientific merit and need. Legal experts at each division of the CHTN and experts at NIH continue to study this area of commercial use of research tissues. Use by Third Parties The CHTN application is intended for the use and processing of samples utilized by the laboratory and/or personnel that fall under the supervision of the Principal Investigator listed in the application. Any transfer of samples or aliquots to personnel or laboratories that are not under the supervision of the indicated Principal Investigator requires the following: An explanation of the need to transfer the materials and benefit to the investigator’s research A copy of the enclosed CHTN agreement page signed by the collaborator A copy of the collaborator’s IRB approval, unless the collaborator is covered under the IRB approval granted for the project proposed in the application. The CHTN does not supply samples to tissue banks solely for distribution to third parties.

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