A
METHODS SECTION: DATA COLLECTION AND ANALYSIS
Introduction
As part of its statement of task, the Health Resources and Services Administration charged the Institute of Medicine Committee on Establishing a National Cord Blood Stem Cell Bank Program to “make recommendations for the optimal structure for the cord blood program and address pertinent issues related to maximizing the potential of this technology (e.g., collection, storage, standard setting, information sharing, distribution, reimbursement, research, and outcome measures).”
To answer the questions posed to them in the statement of task, the committee members used their own technical expertise supplemented by various methods of information gathering. These methods are described below.
Literature Search
The committee used an extensive literature search to compile the relevant data on research on cord blood published to date in the EMBASE, PreMedline, and Medline databases of medical literature. The search was conducted in two parts. The first focused on cord blood banking issues limited to human subjects, using the keyword terms: (“blood banks” OR “blood donors” OR “Blood blood preservation” OR “preservation, biological” OR “cryopreservation” OR “freeze drying”) AND (“fetal blood” OR “hematopoietic stem cells”). This search generated 1,274 articles. The second search looked specifically at cord blood in hematopoietic progenitor
cell (HPC) transplantation and at HPC transplantation in general, using the key terms “fetal blood [transplantation]” OR “cord blood stem cell transplantation” OR (“fetal blood” AND “stem cell transplantation”) OR (“umbilical cord blood” AND (“bone marrow transplantation” OR “hematopoietic stem cell transplantation” OR “peripheral blood stem cell”) OR (“umbilical cord blood” AND “stem cell transplantation”). This search was also limited to research with human subjects and provided 870 articles. The breakdown of human subjects described in the articles by age showed that fewer articles described research with adults than research with children and adolescents. The exact number of articles found for each category was: adults, 455 articles; adolescents, 200 articles; children, 271 articles; infants, 130 articles; and infants and newborns, 311 articles. Because cord blood transplantation is a relatively new therapy, the search was not limited by year. Of the 2,144 records in the list, however, only 48 articles dated from before 1980.
Site Visits
At the first meeting, the members of the committee decided that to best characterize the current state of cord blood banking in the United States, they would need to see cord blood banks firsthand. The committee chose a variety of banks with different affiliations, sizes, and objectives to best represent the diversity of the cord blood banking industry. The committee saw both private and public banks, as well as banks that focused on directed donations. Committee representation varied for each visit to allow each committee member to see some banks.
At each bank, members of the committee asked the staff of the bank to guide them through the path of a cord blood unit from the moment that it arrives at the bank, through all processing, to the moment that the unit is frozen in storage. Specific attention was paid to the individual banks’ approaches to
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consent,
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collection processes,
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decisions about minimum levels for storage and for transplant,
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labeling and identification,
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processing,
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informatics and databases,
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matching, and
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shipping.
A list of the sites visited is in Box A-1.
BOX A-1
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Survey
No comprehensive data were available about indicators such as the racial makeup of cord blood donors or the cost of storage of each unit in the cord blood inventory in the United States. For this reason, the members of the committee set about gathering these data themselves.
To gather these more quantitative data, the members of the committee asked cord blood banks for information in the form of a questionnaire, which was sent to 40 cord blood banks in the United States. The questions asked for:
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general background information;
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collection and storage;
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inventory size and composition;
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cost, either for storage or as reimbursements from a transplant facility; and
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the procedures used to search for matches and use of cord blood units (completed only if services include public banking).
In addition to mailing the survey to 40 banks, the survey was also made available online (see Appendix B). The surveys were sent with prestamped, return-addressed envelopes, and second and third follow-up letters were sent to thank the banks that had responded and to request responses from those that had not yet done so. As of November 18, 2004, the committee had received 21 partially or fully completed surveys. The information gathered helped the committee make its recommendations.
Raw Data Analysis
Although most public banks attempt to maintain more or less complete sets of outcomes data and follow up with recipients of cord blood months and years after the transplant, many are not able to obtain the information; and even among those that can, the data are not usually shared among the different cord blood banks. The committee was given access to the outcomes data from the National Marrow Donor Program cord blood transplants, the results of the COBLT study, and the data from the New York Blood Center and did its own analysis (see Appendix G).
Commissioned Papers
The committee selected several areas in which it wanted analyses to be conducted by experts: human leukocyte antigen typing, the racial make-up and diversity needs of a national inventory, economic issues associated with cord blood banking, and future prospects for cord blood use. These papers were written by Karen Ballen, Margaret Goodell, David Howard, and Carolyn Hurley, respectively. Some of those papers can be found in Appendixes D to F.
Committee Meetings
The committee held two information-gathering meetings before commencing with the writing of the final report.
The first meeting, held on June 2 and 3, 2004, in Washington, D.C., included speakers involved in creating the legislation relevant to the committee’s charge and speakers from selected federal agencies and professional organizations, as well as a speakers presenting the clinical perspective on cord blood transplantation.
At the second meeting, held August 18 and 19, 2004, in Irvine, California, the committee heard from speakers on the topics of informatics and matching algorithms, cord blood bank accreditation, cord blood collection and preservation issues, ethical and legal considerations, outcomes data, and patient support issues. Speakers were chosen for their expertise in their fields.
In addition, periods for participants to make open comments were included during each of the first two meetings. These allowed members of the public representing various constituencies and interested groups to address the committee.
The third and fourth meetings, held September 29 and 30, 2004, in Woods Hole, Massachusetts, and December 15 and 16, 2004, in Washington, DC, respectively, were deliberative and writing meetings, during which
the committee developed and refined its recommendations and the members of the committee worked together to draft the report. The committee also kept in close contact by telephone and electronic communication.
Invited Participants and Guests
The following individuals were invited participants and guests at meetings of the committee.
James Burdick, M.D.
Health Resources and Services Administration
Shelly Carter, Sc.D.
The EMMES Corporation
Jeffrey Chell, M.D.
National Marrow Donor Program
Phil Coelho
Thermogenesis Corporation
Dennis Confer, M.D.
National Marrow Donor Program
Jeff Couglin
American Society for Hematology
Michael Fitzpatrick
America’s Blood Centers
Captain Robert Hartzman
Director, Department of Defense Marrow Program, Navy
Liana Harvath, Ph.D.
National Institutes of Health
Valerie Hurt
National Institutes of Health Office of the General Counsel
Brent Jaquet
Congressman William Young’s Office, Florida
Naynesh Kamani, M.D.
Children’s National Medical Center
Joanne Kurtzberg, M.D.
Duke University Pediatric Stem Cell Transplant Center
Ellen Lazarus, M.D.
Food and Drug Administration
David Leitch
Illinois House of Representatives
Pam Murph, LCSW
Association of Oncology Social Workers
Sudip Parikh
Senator Arlen Specter’s Office, Pennsylvania
Pablo Rubenstein, M.D.
National Cord Blood Program of the New York Blood Center
Karen Shoos-Lipton
American Association of Blood Banks
Edward Snyder, M.D.
American Association of Blood Banks
Cladd Stevens, M.D., MPH
National Cord Blood Program of the New York Blood Center
Susan Stewart
BMTInfonet
Elizabeth Wagner
National Heart, Lung, and Blood Institute
Phyllis Warkentin, M.D.
Foundation for the Accreditation of Cellular Therapy
Jill Warner, Esq.
Food and Drug Administration
Thomas Weigand
Operations Manager, Caitlin Raymond International Registry